Panax ginseng root, not leaf, can enhance thermogenic capacity and mitochondrial function in mice.
Context: Panax ginseng C. A. Meyer (Araliaceae) root and leaf have always been considered in the traditional theory as hot and cold properties, respectively.Objective: To clarify the hot and cold properties of ginseng root and leaf from a thermodynamic viewpoint.Materials and methods: Thirty ICR male mice were randomly assigned to control (water), ginseng root group (GRP) and ginseng leaf group (GLP) with a concentration of 0.075 g/mL; the volume was 0.1 mL/10 g (body mass) per day by intragastric administration for 20 days. Ultra-Performance Liquid Chromatography (UPLC) was used to determine quality control through seven ginsenosides contained in ginseng root and leaf. Rest metabolic rate (RMR) and energy expenditure were monitored every 9 days by TSE System. At the 20th day, serum T3 or T4, liver or brown adipose tissue (BAT) mitochondrial respiration were investigated.Results: The quality control of GRP and GLP were within requirements of 2015 China Pharmacopoeia. The RMR (mLO2/h) in GLP (47.95 ± 4.20) was significantly lower than control (52.10 ± 4.79) and GRP (55.35 ± 4.48). Mitochondrial protein concentration and respiration were significantly increased in GRP (BAT, 79.12 ± 2 .08 mg/g, 239.89 ± 10.24 nmol O2/min/g tissue; Liver, 201.02 ± 10.89, 202.44 ± 3.24) and decreased in GLP (BAT, 53.42 ± 3.48, 153.49 ± 5.58; Liver, 138.69 ± 5.69, 104.50 ± 6.25) compared with control.Conclusions: The hot and cold properties of ginseng root and leaf are correlated with thermogenic capacity and mitochondrial function of BAT and liver, which deserve to further research.


Putting the party down on paper: a novel method for mapping youth drug use in private settings.
This article proposes a novel method for generating context-rich knowledge about 'hard-to-access' places. We ground our discussion in a recent qualitative study of social settings of youth drug use in Denmark. The study confirmed that private house parties are common sites of youth drug use, although these parties presented limited opportunities for fieldwork. In response, a 'map-task' was introduced to the study to complement fieldwork and interviews. We assess the most significant methodological and epistemological features of this map-task, and explore how it may to used to conduct observations 'from a distance' in hard-to-access places. Further, we argue that the map-task has a number of analytical and logistical advantages for scholars interested in the health and social aspects of 'hidden' phenomena, such as youth drug use.


Pressure-Sensitive Conducting and Antibacterial Materials Obtained by in Situ Dispersion Coating of Macroporous Melamine Sponges with Polypyrrole.
Melamine sponges were coated with polypyrrole during the in situ polymerization of pyrrole. The precipitation polymerization was compared with the dispersion mode, that is, with the preparation in the presence of poly(N-vinylpyrrolidone) and nanosilica as colloidal stabilizers. The coating of sponges during the dispersion polymerization leads to the elimination of the undesired polypyrrole precipitate, improved conductivity, and increased specific surface area. The sponges were tested with respect to their conductivity and as pressure-sensitive conducting materials with antibacterial performance.


Legionella and other gram-negative bacteria in potable water from various rural and urban sources.
A total of 107 potable water samples were collected from various rural and urban sources located in the Lublin region (eastern Poland). 54 samples from rural sources comprised 32 samples of untreated well water and 22 samples of treated (chlorinated) tap water from rural dwellings distributed by the municipal water supply system (MWSS). 53 samples of treated water from urban sources were supplied by the city of Lublin MWSS. They comprised: 11 samples of tap water from offices and shops, 8 samples of tap water from dwellings, 19 samples from showerheads in health care units, and 15 samples from the outlets of medical appliances used for hydrotherapy in a rehabilitation centre. Water samples were examined for the presence and species composition of Legionella, Yersinia, Gram-negative bacteria belonging to family Enterobacteriaceae (GNB-E) and Gram-negative bacteria not belonging to family Enterobacteriaceae (GNB-NE), by filtering through cellulose filters and culture on respectively GVPC, CIN, EMB and tryptic soya agar media. Legionella was recovered from samples of well water, tap water from rural dwellings, tap water from urban dwellings, and water from medical appliances - with the isolation frequency of 27.8-50.0 %, and the low concentrations ranging from 0.7-13.3 x 10 (1) cfu/l. No Legionella strains were detected in tap water from offices and shops, and in water from showerheads in health care units. Strains of the Legionella pneumophila types 2-14 predominated, forming 89.9 % of total Legionella isolates, while other species of Legionella formed 10.1 %. Neither Legionella pneumophila type 1 strains nor Yersinia strains were isolated from the examined water samples. The isolation frequency and mean concentration of GNB-E in water samples from rural sources was significantly greater than in water samples from urban sources (respectively 61.1 % vs. 20.8 %, 17.1 vs. 3.4 x 10(1) cfu/l, p < 0.001). Isolation frequency of GNB-NE in water samples from rural sources was significantly greater compared to that from urban sources (77.8 % vs. 47.2 %, p < 0.01), but there was no significant difference in the concentration of GNB-NE in both sample sets. A significant correlation was found between concentrations of Legionella and GNB-NE for total MWSS water samples (p < 0.001), but not for the total well water samples. Altogether 34 GNB-E and GNB-NE species and/or genera were identified in the examined samples, out of which 21 were potentially pathogenic. Enterobacter spp., Klebsiella spp., Serratia spp., and Pantoea agglomerans were most common among GNB-E, while Acinetobacter spp. and species of Pseudomonadaceae family predominated among GNB-NE.


Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know.
Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.


[Evaluation of false-negative lymph nodes diagnosed by fludeoxy glucose-positron emission tomography in cases of metastatic esophageal squamous cell carcinoma].
We have encountered many cases wherein the metastatic nest of esophageal squamous cell carcinoma occupied only a small space in the lymph nodes because of which computed tomography( CT) and fludeoxy glucose( FDG)-positron emission tomography( PET) could not detect the lymph node metastasis satisfactorily. The false-negative lymph nodes that were not detected by FDG-PET before surgery were smaller in diameter, rate of occupation, and area of occupation than the true-positive lymph nodes. The smallest area of the cancer nest in the true-positive group was 7.5 mm2, and therefore, it was reasonable to consider a 5-mm diameter area as the criteria for correct diagnosis by FDG-PET. Most of the false-negative lymph nodes with a large area of carcinoma were attached to the primary tumor; therefore, they could not be precisely identified. The detection of false-negative lymph nodes by FDG-PET was not precise because of increases in the quantity of stroma-like cells in poorly differentiated carcinomas and in fibrosis caused by neoadjuvant therapy in the lymph nodes.


The role of the cell walls in Ni binding by plant roots.
The role of the cell wall in short-term Ni uptake at different solution Ni levels was investigated in mung bean (Vigna radiata (L.) R. Wilczek) and wheat (Triticum aestivum L., cv. Inna). Both Ni-binding capacity of the CWs and roots are lower for wheat than for mung bean at all Ni levels in the solution. For both plants amounts of Ni associated with roots and root cell walls increased with Ni concentration. The contribution of CWs to Ni absorption by roots depends on Ni level in the medium and plant species. The Ni accumulated in CWs could account for total Ni content of roots (except for wheat in highest Ni treatment). Besides, mung bean plants employ the strategy of reducing Ni accumulation in the root CWs during exposure to excess but not toxic solution Ni level. According to the results, predominant Ni binding in the apoplast of mung bean and wheat roots is observed at both high and low external Ni, which suggests that apoplastic pathway is the main means of Ni transport in the root cortex of these species.


Sensitivity of the mouse to changes in azimuthal sound location: angular separation, spectral composition, and sound level.
Auditory spatial acuity was measured in mice using prepulse inhibition (PPI) of the acoustic startle reflex as the indicator response for stimulus detection. The prepulse was a "speaker swap" (SSwap), shifting a noise between two speakers located along the azimuth. Their angular separation, and the spectral composition and sound level of the noise were varied, as was the interstimulus interval (ISI) between SSwap and acoustic startle reflex elicitation. In Experiment 1 a 180 degrees SSwap of wide band noise (WBN) was compared with WBN Onset and Offset. SSwap and WBN Onset had near equal effects, but less than Offset. In Experiment 2 WBN SSwap was measured with speaker separations of 15, 22.5, 45, and 90 degrees . Asymptotic level and the growth rate of PPI increased with increased separation from 15 to 90 degrees , but even the 15 degrees SSwap provided significant PPI for the mean performance of the group. SSwap in Experiment 3 used octave band noise (2-4, 4-8, 8-16, or 16-32 kHz) and separations of 7.5 to 180 degrees . SSwap was most effective for the highest frequencies, with no significant PPI for SSwap below 8-16 kHz, or for separations of 7.5 degrees . In Experiment 4 SSwap had WBN sound levels from 40 to 78 dB SPL, and separations of 22.5, 45, 90, and 180 degrees : PPI increased with level, this effect varying with ISI and angular separation. These experiments extend the prior findings on sound localization in mice, and the dependence of PPI on ISI adds a reaction time-like dimension to this behavioral analysis.


Radiation-induced erectile dysfunction: Recent advances and future directions.
Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT) as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED) because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to mitigate or cure sexual dysfunction following radiation treatment.


Optimized transfection of diced siRNA into mature primary human osteoclasts: inhibition of cathepsin K mediated bone resorption by siRNA.
Osteoclasts are large multinucleated cells responsible for bone resorption. Bone resorption is dependent on the liberation of calcium by acid and protease destruction of the bone matrix by proteinases. The key proteinase produced by the osteoclast is cathepsin K. Targeted knock-down of cathepsin K was performed using small inhibitory RNA (siRNA). siRNA is a method that introduces short double-stranded RNA molecules that instruct the RNA-induced silencing complex (RISC) to degrade mRNA species complementary to the siRNA. Transfection of siRNA by lipid cations allows for short-term inhibition of expression of the targeted gene. We show that transfection of primary human osteoclasts with siRNA to cathepsin K reduces expression by > or = 60% and significantly inhibits bone resorption with a reduction of both resorption pit numbers (P = 0.018) and resorbed area (P = 0.013). We also show that FuGENE 6 is an effective lipid transfection reagent with which to transfect primary human osteoclasts, that does not produce off-target effects.


Primary B-cell lymphoma presenting as bilateral ear lobule swelling.
We report a rare case of primary B-cell lymphoma presenting as bilateral ear lobule swelling. A 56-year-old white man presented with a one-year history of painless swelling of both ear lobules. An excision biopsy confirmed B-cell lymphoma. Detailed systemic investigation confirmed the primary nature of the tumour. This tumour is rare in the ear lobule. A review of the English literature revealed no previously reported case of bilateral primary ear lobule involvement. Clinicians should be aware that this tumour can present as a primary in the ear lobules.


Anaplastic Oligodendroglioma Found as an Incidental Photopenic Lesion on 18F-FP-CIT PET/CT Image.
F-FP-CIT PET is a useful modality for imaging dopamine transporters. It has excellent resolution compared with I-beta-CIT SPECT and is widely used clinically for the evaluation of Parkinson disease. In general, the main focus of F-FP-CIT PET imaging is the basal ganglia, and it is important to observe whether F-FP-CIT uptake is normal in the putamen and caudate nuclei. However, abnormal findings may be seen in other brain regions besides the basal ganglia. Here, we present a case of anaplastic oligodendroglioma, a high-grade tumor, which was found as an incidental photopenic lesion on F-FP-CIT PET/CT.


Impact of FMD outbreak on milk production and heifers' growth on a dairy herd in southern Iran.
Foot and mouth disease is endemic in Middle Eastern countries including Iran but its impact is poorly characterized. The present study was conducted to evaluate the impact of FMD outbreak on milk production and heifers' growth in an industrial dairy herd located in Fars province, southern Iran. Data about individual milk production, heifers' growth and total daily milk (sold for manufacturing), its fat and protein content and somatic cell counts were collected from the herd database. Based on the results of the linear mixed models, a significant decline in individual milk production after the outbreak was observed compared with before the outbreak. There was a total reduction of 8.0 and 4.7% in mean daily milk production per cow after the outbreak when compared with before (over a 42days outbreak period) in lactation one (P<0.001) and lactation ≥2 cows (P=0.024), respectively. The total daily milk (P=0.027) and protein (P=0.002) showed significant decline during the outbreak period. The fat content decreased after the outbreak (P=0.014). Somatic cell counts did not show significant changes. The recorded heifers' weights (4-17 months of age) showed 7.1kg decrease after the outbreak in comparison with the period before that (P<0.001). In conclusion, we observed a negative impact of FMD outbreak on milk production and heifers' growth in study herd. The impact on daily milk production was less than the values reported previously. This difference could be attributed at least partly to differences in livestock genetics and management practices. Lower growth rate of heifers after the outbreak period could potentially extend the age at first calving. It is suggested that farmers are educated on awareness and preparation for infectious disease outbreaks and to practice good management routines that could potentially reduce the economic impact of these diseases.


Identification of putative amine biosynthetic enzymes in the nervous system of the crab, Cancer borealis.
Amines function as neuromodulators throughout the animal kingdom. In decapod crustaceans, the amines serving neuromodulatory roles include dopamine, octopamine, serotonin and histamine. While much work has focused on examining the physiological effects of amines on decapod nervous systems, the identity of the native enzymes involved in their biosynthesis remains largely unknown. In an attempt to help fill this void, a transcriptome generated from multiple portions of the crab, Cancer borealis, nervous system, a species that has long served as a model species for investigating the neuromodulatory control of rhythmically active neural networks, was used to identify putative amine biosynthetic enzyme-encoding transcripts, and by proxy, proteins. Transcripts encoding full complements of the enzymes involved in the production of dopamine, octopamine, serotonin, and histamine were deduced from the C. borealis assembly, i.e., tryptophan-phenylalanine hydroxylase, tyrosine hydroxylase, DOPA decarboxylase, tyrosine decarboxylase, tyramine β-hydroxylase, tryptophan hydroxylase, and histidine decarboxylase. All proteins deduced from the C. borealis transcripts appear to be full-length sequences, with reciprocal BLAST and structural domain analyses supporting the protein family annotations ascribed to them. These data provide the first descriptions of the native amine biosynthetic enzymes of C. borealis, and as such, serve as a resource for initiating gene-based studies of aminergic control of physiology and behavior at the level of biosynthesis in this important biomedical model.


Inhibition of estrone sulfate-induced uterine growth by potent nonestrogenic steroidal inhibitors of steroid sulfatase.
The present study describes the biological in vitro and in vivo evaluation of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, namely 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)-1,3,5 (10)-estratrien-17beta-ols. The addition of the 2-methoxy group conserves the potent inhibitory effect on steroid sulfatase activity (IC(50)s of 0.024 and 0.040 nM) while removing the estrogenic action. Using an ovariectomized mouse model, we show that the first generation of steroid sulfatase inhibitors tested, 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)estra-1,3,5 (10)-trien-17beta-ols and estrone-3-O-sulfamate, are estrogenic compounds stimulating estrogen-sensitive uterine growth. Interestingly, the 2-methoxy-3-sulfamoyloxy-17alpha-benzylestra-1,3,5 (10)-trien-17beta-ol (7) has no estrogenic activity but efficiently blocks (s.c. and p.o.) uterine growth induced by estrone sulfate, which is converted into estrone and then estradiol by steroid sulfatase and type 1 17beta-hydroxysteroid dehydrogenase, respectively. This report clearly shows that a steroid sulfatase inhibitor can efficiently block estrogen action from the inactive precursor estrone sulfate, in vitro and in vivo.


[Resuscitation of elderly people : how to approach their preferences in advance].
Cardiopulmonary resuscitation (CPR) is a medical intervention whose practice is highly regulated. In Switzerland, when dealing with elderly patients, physicians decide whether resuscitation would be medically indicated in the case of a cardiorespiratory arrest and discuss it with the patient. The quality of the information provided by the physician during the first encounter with the patient may influence the latter's preferences. However, many studies emphasize the difficulties that hospital physicians face when engaging in this conversation. In order to promote a care provision that is both adequate and respectful of elderly patients, more attention should be devoted to the obstacles that hinder communication on this subject and to the resources available to physicians.


How does sodium lauryl sulfate alter the skin barrier function in man? A multiparametric approach.
The effects of topically applied sodium lauryl sulfate were studied in vivo, in man, through noninvasive methods and compared with those obtained in vitro, using human stratum corneum as a model. The results show that the very marked increase of transepidermal water loss obtained in vivo cannot be related to any removal of epidermal lipids. The most likely explanation of our findings lies in the hyperhydration of stratum corneum consecutive to the inflammation process and a possible disorganization of the lipid bilayers.


Contrast-enhanced ultrasound combined targeted microbubbles for diagnosis of highly aggressive papillary thyroid carcinoma.
Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC. To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC. Using β-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system. Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 μm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs. We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.


Long Non-Coding RNA as Potential Biomarker for Prostate Cancer: Is It Making a Difference?
Whole genome transcriptomic analyses have identified numerous long non-coding RNA (lncRNA) transcripts that are increasingly implicated in cancer biology. LncRNAs are found to promote essential cancer cell functions such as proliferation, invasion, and metastasis, with the potential to serve as novel biomarkers of various cancers and to further reveal uncharacterized aspects of tumor biology. However, the biological and molecular mechanisms as well as the clinical applications of lncRNAs in diverse diseases are not completely understood, and remain to be fully explored. LncRNAs may be critical players and regulators in prostate cancer carcinogenesis and progression, and could serve as potential biomarkers for prostate cancer. This review focuses on lncRNA biomarkers that are already available for clinical use and provides an overview of lncRNA biomarkers that are under investigation for clinical development in prostate cancer.


Making sense of hormone-mediated defense networking: from rice to Arabidopsis.
Phytohormones are not only essential for plant growth and development but also play central roles in triggering the plant immune signaling network. Historically, research aimed at elucidating the defense-associated role of hormones has tended to focus on the use of experimentally tractable dicot plants such as Arabidopsis thaliana. Emerging from these studies is a picture whereby complex crosstalk and induced hormonal changes mold plant health and disease, with outcomes largely dependent on the lifestyle and infection strategy of invading pathogens. However, recent studies in monocot plants are starting to provide additional important insights into the immune-regulatory roles of hormones, often revealing unique complexities. In this review, we address the latest discoveries dealing with hormone-mediated immunity in rice, one of the most important food crops and an excellent model for molecular genetic studies in monocots. Moreover, we highlight interactions between hormone signaling, rice defense and pathogen virulence, and discuss the differences and similarities with findings in Arabidopsis. Finally, we present a model for hormone defense networking in rice and describe how detailed knowledge of hormone crosstalk mechanisms can be used for engineering durable rice disease resistance.


Switching cell fate, ncRNAs coming to play.
Cell fate decision is a critical step during physiological development when embryonic stem cells commit to either becoming adult stem cells or somatic cells. Recent advances in reprogramming demonstrate that a similar set of transcription factors (TFs), which are important for maintaining the pluripotent state of stem cells, can also reprogram somatic cells to induced pluripotent stem cells (iPSCs). In addition, trans-differentiation, which entails the use of different sets of defined factors, whereby one type of somatic cell can be directly converted into another and even to cell types from different germ layers has become a parallel widely used approach for switching cell fate. All these progresses have provided powerful tools to manipulate cells for basic science and therapeutic purposes. Besides protein-based factors, non-coding RNAs (ncRNAs), particularly microRNAs and long ncRNAs, are also involved in cell fate determination, including maintaining self-renewal of pluripotent stem cells and directing cell lineage. Targeting specific ncRNAs represents an alternative promising approach to optimize cell-based disease modeling and regenerative therapy. Here we focus on recent advances of ncRNAs in cell fate decision, including ncRNA-induced iPSCs and lineage conversion. We also discuss some underlying mechanisms and implications in molecular pathogenesis of human diseases.


Ectotherms in Variable Thermal Landscapes: A Physiological Evaluation of the Invasive Potential of Fruit Flies Species.
Climate change and biological invasions pose one of the greatest threats to biodiversity. Most analyses of the potential biological impacts have focused on changes in mean temperature, but changes in thermal variance may also impact native and invasive organisms, although differentially. We assessed the combined effects of the mean and the variance of temperature on the expression of heat shock protein (hsp90) in adults of the invasive fruit fly Drosophila melanogaster and the native Drosophila gaucha in Mediterranean habitats of central Chile. We observed that, under these experimental conditions, hsp90 mRNA expression was higher in the invasive species but absent in the native one. Apparently, the biogeographic origin and niche conservatisms are playing a role in the heat shock response of these species under different putative scenarios of climate change. We suggest that in order to develop more realistic predictions about the biological impact of climate change and biological invasions, one must consider the interactions between the mean and variance of climatic variables, as well as the evolutionary original conditions of the native and invasive species.


Pain Catastrophizing and Its Relationship with Health Outcomes: Does Pain Intensity Matter?
Pain catastrophizing is known to contribute to physical and mental functioning, even when controlling for the effect of pain intensity. However, research has yet to explore whether the strength of the relationship between pain catastrophizing and pain-related outcomes varies across pain intensity levels (i.e., moderation). If this was the case, it would have important implications for existing models of pain and current interventions. The present investigation explored whether pain intensity moderates the relationship between pain catastrophizing and pain-related outcomes. Participants were 254 patients (62% women) with heterogeneous chronic pain. Patients completed a measure of pain intensity, pain interference, pain catastrophizing, and physical and mental health. Pain intensity moderated the relationship between pain catastrophizing and pain interference and between pain catastrophizing and physical health status. Specifically, the strength of the correlation between pain catastrophizing and these outcomes decreased considerably as pain intensity increased. In contrast, pain intensity did not moderate the relationship between pain catastrophizing and mental health. Study findings provide a new insight into the role of pain intensity (i.e., moderator) in the relationship between pain catastrophizing and various pain-related outcomes, which might help develop existent models of pain. Clinical implications are discussed in the context of personalized therapy.


What does it cost Medicare to diagnose and treat men with localized prostate cancer in the first year?
To estimate costs on the Medicare Benefits Schedule (MBS) and the Pharmaceutical Benefits Scheme (PBS) attributable to the diagnosis and treatment of prostate cancer. We used data from a cohort study of 1064 men with localized prostate cancer recruited between 2005 and 2007 by 24 urologists across 10 sites in Queensland, Australia (ProsCan). We estimated the MBS and PBS costs attributable to prostate cancer from the date of initial appointment to 12 months after diagnosis in 2013 Australian dollars using a comparison group without prostate cancer. We used generalized linear modeling to identify key determinants of higher treatment-related costs. From the date of initial appointment to 12 months postdiagnosis, the average MBS costs attributable to prostate cancer were $9,357 (SD $191) per patient. These MBS costs were most sensitive to having private health insurance and the type of primary treatment received. The PBS costs were higher in the control group than in the ProsCan group ($5,641 vs $1,924). The costs of treating and managing prostate cancer are high and these result in a substantial financial burden for the Australian MBS. Costs attributable to prostate cancer appear to vary widely based on initial treatment and these are likely to increase with the introduction of more expensive services and pharmaceuticals. There is a pressing need for better prognostic tools to distinguish between indolent and aggressive prostate tumors to reduce potential over treatment and help ease the burden of prostate cancer.


Cloning and characterization of OsORC2, a new member of rice origin recognition complex.
In eukaryotic cells, the origin recognition complex (ORC) governs the initiation site of DNA replication and formation of the prereplication complex. The isolation, characterization and tissue-specific expression of a putative ORC subunit 2 (OsORC2) in Oryza sativa is described here. A novel cDNA fragment encoding rice ORC2 was isolated by screening the subtractive library, which had a higher expression level in inflorescence meristem than in shoot apical meristem. The full-length cDNA of rice ORC2 was obtained by the method of rapid amplification of cDNA ends, which contained an 1140 bp open reading frame encoding a 379 amino acid polypeptide. Sequence alignment shows that there is a high homology between the deduced amino sequence of OsORC2 and maize ORC2 (85%). The tissue-specific expression pattern of OsORC2 reveals that it is abundant in roots, seedling and inflorescence meristem, while its expression level is much lower in mature leaves and shoot.


Novel Zeolite-5A@MOF-74 Composite Adsorbents with Core-Shell Structure for H2 Purification.
Hydrogen is considered as one of the most important clean and renewable energy sources for a sustainable energy future. However, its efficient and cost-effective purification still remains challenging. In this work, we report the development of novel zeolite@metal-organic framework (MOF) composites comprised of MOF-74 and zeolite-5A with core-shell structure for efficient purification of H2. The composites were synthesized hydrothermally through the addition of zeolite particles with and without carboxyl functional groups to the MOF synthesis solution. The zeolite/MOF weight ratio was varied systematically to find the optimum composition based on the adsorption performance. The formation of zeolite@MOF composites was confirmed by various characterization techniques. Single-component adsorption isotherms of CO2, CO, CH4, N2, and H2 over composites were measured at 25 °C to determine their equilibrium adsorption capacity. It was found that the zeolite-5A@MOF-74 with weight ratio of 5:95 exhibited a similar morphology to that of pristine MOF-74, but with higher surface area and total pore volume. Moreover, this composite showed 20-30% increase in CO2, CO, CH4, and N2 uptake than the bare MOF, which could be attributed to the formation of new mesopores at the MOF-zeolite interface. The estimated selectivity values for CO2/H2, CO/H2, CH4/H2, and N2/H2 were higher than those of the zeolite and/or MOF. Our results also indicated that surface modification of zeolite prior to composite formation does not enhance the adsorption capacities of the composites. Overall, the findings of this study suggest that the zeolite-5A@MOF-74 composites with core-shell structure are promising candidates for industrial H2 purification processes.


Inhibition of insulin degradation by nonsuppressible insulin-like activity.
Nonsuppressible insulin-like activity, provided by three sources, was evaluated for its effect on the proteolytic degradation of insulin utilizing insulin protease obtained from rat liver homogenate as well as liver cell membranes. All three preparations of nonsuppressible insulin-like activity were found to be competitive inhibitors of insulin degradation. In addition human plasma was fractionated yielding an acetone precipitate which was found to have nonsuppressible insulin-like activity and to be a competitive inhibitor of insulin protease.


Pneumocystis carinii pneumonia complicating low dose methotrexate treatment for psoriatic arthropathy.
A case of Pneumocystis carinii pneumonia complicating low dose methotrexate treatment for psoriasis and psoriatic arthropathy is described. This potentially fatal event was probably precipitated by an interaction between methotrexate and concurrent non-steroidal anti-inflammatory drugs, resulting in serious potentiation of the effects of methotrexate.


Identification of key structural characteristics of Schisandra chinensis lignans involved in P-glycoprotein inhibition.
The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.


Is coma morally equivalent to anencephalia?
In this article I contend that the tendency to equate coma with anencephalia is a mistake. A key idea here is that there is a type of "mental-state" predicate that is applicable to the comatose but not to anencephalics. One of the moral implications of this is that the concept of "brain death," its alleged popularity notwithstanding, is badly confused. Also, because anencephalics have no mental life, there are few moral grounds for hesitating to use anencephalics as organ donors.


Identification of serum-responsive elements in the promoter of human calcyclin, a growth-regulated gene.
The calcyclin gene is growth regulated in a number of cell types from different animal species. We have identified in the promoter region of the human calcyclin gene the sequences responsible for its growth regulation by serum. A number of deletion mutants and synthetic nucleotides, all driving the chloroamphenicol transferase (CAT) gene, were constructed for this purpose. Serum-responsive elements can be localized in the last 42 bp immediately upstream from the CAP site.


Hyperfine-Interaction-Driven Suppression of Quantum Tunneling at Zero Field in a Holmium(III) Single-Ion Magnet.
An extremely rare non-Kramers holmium(III) single-ion magnet (SIM) is reported to be stabilized in the pentagonal-bipyramidal geometry by a phosphine oxide with a high energy barrier of 237(4) cm-1 . The suppression of the quantum tunneling of magnetization (QTM) at zero field and the hyperfine structures originating from field-induced QTMs can be observed even from the field-dependent alternating-current magnetic susceptibility in addition to single-crystal hysteresis loops. These dramatic dynamics were attributed to the combination of the favorable crystal-field environment and the hyperfine interactions arising from 165 Ho (I=7/2) with a natural abundance of 100 %.


Vasopressin release induced by hypothension is blunted in patients with diabetic autonomic neuropathy.
The response of arginin-vasopressin (AVP) to baroreceptor activation (tilt testing) was investigated in patients with diabetic autonomic neuropathy (DAN). The present data show that hypothension induced by upright position showed a slight increase of AVP in patients with DAN in comparison with normal subjects and diabetic patients without DAN. These findings suggest that the blunted AVP response to hypothension may be due to lesions of afferent autonomic pathways present in DAN and plays a role in the pathogenesis of postural hypothension.


Theoretical study on the assembly and stabilization of a magic cluster Al4N-.
We report the first attempt to assemble the magic cluster Al4N- on the basis of the density functional theory calculations on a series of pi-stacked dimers (Al4N-)2, sandwich-like compounds [D(Al4N)M]q- (where D = Al4N-, Cp-(C5H5-); M = Li, Na, K, Be, Mg, Ca) and extended compounds (Cp-)m(Li+)n(Al4N-)o (where m, n, and o are integers). For the six metals, the magic Al4N- can only be assembled and grow up in our newly proposed "hetero-decked sandwich" scheme (e.g., [CpM(Al4N)]q-) so as to avoid cluster fusion. The ground-state hetero-decked sandwich species (Cp-)(M)q+(Al4N)- (M = Li, Na, K, q = 1; M = Be, Mg, Ca, q = 2) and the extended sandwich species (Cp-)m(Li+)n(Al4N-)o are mainly ionically bonded, cluster-assembled "polyatomic molecules", grown from the combination of Cp-, M-atoms, and Al4N-. As a prototype for ionic bonding involving intact Al4N- subunits, [CpM(Al4N)]q- may be a stepping stone toward forming ionic, cluster-assembled AlN compounds.


Intraocular surgery with melphalan irrigation for vitreous hemorrhage in an only eye with retinoblastoma.
To illustrate the successful outcome of pars plana vitrectomy (PPV) with melphalan irrigation for vitreous hemorrhage (VH) with suspected viable retinoblastoma. Despite the high risk of intraocular surgery, it was performed to preserve the only potentially seeing eye with treated retinoblastoma. Vitreous hemorrhage occurred in the only eye of a 4-year-old boy after treatment for recurrent multifocal group C retinoblastoma with systemic chemotherapy (carboplatin, etoposide, and cyclophosphamide; and vincristine, cyclophosphamide, and doxorubicin), ruthenium brachytherapy with plaque repositioning, cryotherapy, and external radiotherapy. The VH developed 8 months after repeated brachytherapy with subsequent intravitreal melphalan chemotherapy. The patient's parents refused to remove the eye. The fellow eye was enucleated earlier because of VH and secondary glaucoma, without histologic signs of a viable tumor. Pars plana lensectomy, 25-G vitrectomy with melphalan irrigation (5 μg/mL), and silicone oil tamponade were performed. No ophthalmoscopic or morphologic signs of a viable tumor were detected. Four months later, the silicone oil was removed. Visual acuity was 20/200 with aphakic correction. Follow-up for 34 months revealed no signs of tumor recurrence or dissemination. Despite the high risk of intraocular surgery, the need to preserve the only potentially seeing eye with treated retinoblastoma may require PPV. Thus, in unclear cases of VH with suspected viable tumor, PPV with intraocular melphalan irrigation, with caution, may be a reasonable procedure.


Evaluation of the Dose-Dependent Effects of Fermented Mixed Grain Enzyme Food on Adiposity and Its Metabolic Disorders in High-Fat Diet-Induced Obese Mice.
Ancient traditions showed that fermented enzyme foods have beneficial health effects on the body. However, only a few studies have reported on its impact on weight loss and metabolic syndrome. Therefore, it is necessary to verify whether diet supplementation with fermented enzyme foods can have a beneficial functional impact on the body. We examined the antiobesity properties of fermented mixed grain (FMG) with digestive enzymes (FMG) in diet-induced obese mice. Sixty C57BL/6J mice were randomly assigned to six dietary groups: (1) normal diet (ND), (2) high-fat diet (HFD), (3) Bacilus Coagulans, (4) steamed grain, (5) low-dose FMG (L-FMG), and (6) high-dose FMG (H-FMG) supplement for 12 weeks. The results showed that H-FMG supplement dramatically decreased body weight and fat mass with simultaneous decreases in plasma lipid contents. Furthermore, H-FMG significantly lowered fasting blood glucose concentrations and improved glucose tolerance compared with the HFD group. Also, the concentrations of inflammatory cytokines secreted from adipocytes in H-FMG-supplemented mice decreased dramatically. Taken together, our findings indicated that H-FMG can ameliorate HFD-induced obesity and its associated complications and could be used as a potential preventive intervention for obesity.


Control of gene expression through the nonsense-mediated RNA decay pathway.
Nonsense-mediated RNA decay (NMD) was originally discovered as a cellular surveillance pathway that safeguards the quality of mRNA transcripts in eukaryotic cells. In its canonical function, NMD prevents translation of mutant mRNAs harboring premature termination codons (PTCs) by targeting them for degradation. However, recent studies have shown that NMD has a much broader role in gene expression by regulating the stability of many normal transcripts. In this review, we discuss the function of NMD in normal physiological processes, its dynamic regulation by developmental and environmental cues, and its association with human disease.


[A case of ammonium urate urinary stone].
An 18-year-old female, who had undergone antireflux surgery for bilateral vesicoureteral reflux 5 years ago, was admitted to our department with complaints of fever and left-sided back pain. Bilateral renal stones and pyelonephritis were diagnosed after roentgenography, ultrasonography and urinalysis. Pyelonephritis was successfully treated with antibiotics and the left renal stone was completely disintegrated with extracorporeal shock wave lithotripsy. Spectrophotometric analysis revealed that the stone was composed of pure ammonium urate (AU). The patient had not experienced any episodes of urinary tract infection from the antireflux surgery until the present event, but had lost 20 kg in body weight during the last year due to a low-caloric diet and laxative abuse. AU urinary stones have been infrequently reported in Japan, and they are supposed to be associated with a low-caloric diet, laxative abuse, and anorexia nervosa.


Improved techniques for the identification of pseudogenes.
Pseudogenes are the remnants of genomic sequences of genes which are no longer functional. They are frequent in most eukaryotic genomes, and an important resource for comparative genomics. However, pseudogenes are often mis-annotated as functional genes in sequence databases. Current methods for identifying pseudogenes include methods which rely on the presence of stop codons and frameshifts, as well as methods based on the ratio of non-silent to silent nucleotide substitution rates (dN/dS). A recent survey concluded that 50% of human pseudogenes have no detectable truncation in their pseudo-coding regions, indicating that the former methods lack sensitivity. The latter methods have been used to find sets of genes enriched for pseudogenes, but are not specific enough to accurately separate pseudogenes from expressed genes. We introduce a program called pseudogene inference from loss of constraint (PSILC) which incorporates novel methods for separating pseudogenes from functional genes. The methods calculate the log-odds score that evolution along the final branch of the gene tree to the query gene has been according to the following constraints: A neutral nucleotide model compared to a Pfam domain encoding model (PSILC(nuc/dom)); A protein coding model compared to a Pfam domain encoding model (PSILC(prot/dom)). Using the manual annotation of human chromosome 6, we show that both these methods result in a more accurate classification of pseudogenes than dN/dS when a Pfam domain alignment is available. PSILC is available from http://www.sanger.ac.uk/Software/PSILC


A frogspawn-inspired hierarchical porous NaTi2(PO4)3-C array for high-rate and long-life aqueous rechargeable sodium batteries.
Hollow micro/nano-arrays have attracted tremendous attention in the field of energy conversion and storage, but such structures usually compromise the volumetric energy density of the electrode materials. Frogspawn consists of a spawn core and a transparent jelly shell organized in a hierarchical porous array, which exhibits superior mechanical strength and high-efficiency oxygen permeability. It can be used as a model for designing a new high-performance electrode material, which has advantages such as a high surface area, fast mass transport and superior durability. Herein, we report a frogspawn-like NaTi2(PO4)3/C array prepared by a facile preform impregnation strategy. The framework is formed by a hollow carbon sphere connected by the NaTi2(PO4)3/C skeleton, and its hollow is filled with the NaTi2(PO4)3 nanospheres. The whole hierarchical porous three-dimensional array copies the structure of a frogspawn. This unique structure not only enables easy electrolyte percolation and fast electron/ion transport, but also enhances the reversible capacity and cycling durability. When it is applied as an anode of the aqueous sodium ion battery, it exhibits favorable high rate capability and superior cycling stability, and retains 89% of the initial capacity after two thousand cycles at 20 C. Moreover, the full cell using the frogspawn-inspired NaTi2(PO4)3-C as the anode and Na0.44MnO2 as the cathode is capable of ultralong cycling up to one thousand cycles at alternate 10 and 60 C, which is among the best of state-of-the-art aqueous sodium ion systems. Therefore, the frogspawn-inspired architecture provides a new strategy to the tailored design of polyanion materials for high-power applications.


[Cataract surgery with implantation of toric silicone lenses for severe astigmatism after keratoplasty].
The treatment of high astigmatism after keratoplasty is often not possible with glasses or refractive corneal surgery, particularly in patients with anisometropia and contact lens incompatibility. In 3 patients with cataract and high astigmatism after penetrating keratoplasty, phacoemulsification was performed via a 4 mm sclerocorneal tunnel incision. A toric silicone lens with Z-haptic was implanted in the bag (Type MS 6116 TU, Dr. Schmidt). All patients had high anisometropia and contact lens incompatibility. The follow-up was ten weeks, uncorrected and corrected visual acuity, corneal and total astigmatism were evaluated. A 68-year-old female presented with corneal astigmatism of 10 dpt. Keratoplasty was performed two years earlier. After implantation of a toric lens (+ 22.5 + 11.0 dpt.) uncorrected visual acuity increased from 1/50 to 20/40, corrected visual acuity increased from 20/30 to 20/25. A 78-year-old male presented with irregular corneal astigmatism of 6.5 dpt. Keratoplasty was performed 25 years previously. Due to high myopia (corneal radii 5.3/5.9 mm), implantation of a toric lens (- 3.0 + 7.0 dpt.) in the bag was combined with implantation of a spheric lens (- 6.0 dpt., Type MS 614, Dr. Schmidt) in the sulcus. Uncorrected visual acuity increased from light perception to 1/20, corrected visual acuity increased to 1/10. An 84-year-old female presented with irregular corneal astigmatism of 8.6 dpt. Keratoplasty was performed two years earlier. After implantation of a toric lens (+ 16.0 + 11.0 dpt.) uncorrected visual acuity increased to 20/50, corrected visual acuity increased from 20/100 to 20/25. During the follow-up all implanted lenses were well-centered and no significant IOL rotation was observed. Implantation of foldable toric silicone lenses during cataract surgery may improve considerably the uncorrected visual acuity by reducing the total astigmatism in patients with high astigmatism after keratoplasty. Preoperatively, a reliable keratometry is important.


Struma Ovarii with Pseudo-Meigs' Syndrome and Raised Cancer Antigen-125 Levels Masquerading as an Ovarian Carcinoma Case report and literature review.
The monodermal teratoma struma ovarii is a rare ovarian tumour; however, struma ovarii presenting with pseudo-Meigs' syndrome and raised cancer antigen (CA)-125 levels is even rarer. In elderly patients, this presentation can potentially lead to a misdiagnosis of a malignant ovarian carcinoma, resulting in unnecessary extensive surgery. We report a 55-year-old female who presented to the Lok Nayak Jai Prakash Narayan Hospital, New Delhi, India, in 2016 with progressive abdominal discomfort, fatigue and abdominal distention. Clinical and radiological features were indicative of a malignant ovarian tumour and ascites. Serum CA-125 levels were elevated at 258 U/mL. A left-sided salpingo-oophorectomy was performed, after which the serum CA-125 levels normalised. There was no evidence of recurrence at a six-month follow-up. A frozen section procedure confirmed the diagnosis of a struma ovarii. This rare condition should be considered as a differential diagnosis in patients presenting with ovarian masses, ascites and raised CA-125 levels.


[Recurrent urinary tract infections: prevention of recurrence with intravesical instillations of chondroitin sulfate and hyaluronic acid.]
The aim of our study is to demonstrate that intravesical administration of the association chondroitin sulfate (CS) and hyaluronic acid (HA), according to our treatment schedule, is a benefit for women with recurrent urinary tract infections (RUTI), not only from a clinical point of view, but also reducing recurrences. This is a study of 28 women diagnosed with RUTI, with a positive culture, and compatible symptoms;frethey underwent treatment according to the protocol of intravesical instillations of the combination CS 2%-1 gr + HA 1.6%-800 mg. To evaluate the effectiveness of the treatment, symptoms improvement, reduction of the number of episodes of urinary tract infection and quality of life were considered. In our series, we can observe an improvement of the quality of life assessed by PG-I, 66% after 12 months. It was seen that 55.6% of the patient's urine cultures became negative, while 44.4% had episodes of urinary infection, but with lower baseline symptoms intensity. Patients included in the protocol of instillation improved significantly their quality of life; in addition, to a considerable extent new urinary infections were not presented, being milder when they presented.


A new tribe of tarsonemid mites (Trombidiformes: Heterostigmatina) parasitic on tetrigid grasshoppers (Orthoptera).
Podotarsonemini tribe nov. (Tarsonemidae: Acarapinae), with one nominate genus Podotarsonemus gen. nov., is proposed for seven new species of tarsonemid mites collected from the hindwings of pygmy grasshoppers of the family Tetrigidae (Orthoptera). The new tribe is placed within the tarsonemid subfamily Acarapinae on the basis of several morphological synapomorphies, as well as on parasitism of insects. In light of this new tribe, a revised description of the Acarapinae is provided, as are full tribal, generic and species descriptions for the Podotarsonemini, and a key to species. In view of Podapolipidae, the sister family of Tarsonemidae, consisting entirely of obligatory parasitic mites, the distinction between the two constituent sister families of Tarsonemoidea as well as the ancestral feeding habits of that superfamily are considered. These mites and their host grasshoppers were collected from Bolivia, Ecuador, Honduras, southern India, Japan, Papua New Guinea, South Africa and two localities in north-eastern Australia. This distribution suggests that the Podotarsonemini are an ancient lineage of Tarsonemidae that radiated on the Gondwanan Tetrigidae during the Jurassic.


A family of RTHβ with p.R316C mutation presenting occasional syndrome of inappropriate secretion of TSH.
The syndrome of inappropriate secretion of thyrotropin (SITSH) is a hallmark of resistance to thyroid hormone (RTH) due to mutations in the β isoform of the thyroid hormone receptor (TRβ). Here, we report on a family of RTH due to a TRβ mutation (RTHβ) and presenting occasional SITSH. The proband was a 16 year-old girl with a goiter, detected at a school physical examination. She was initially diagnosed as having euthyroid Hashimoto thyroiditis because her thyroid function was normal with a positive anti-thyroglobulin antibody. Follow-up examinations resulted in mild SITSH on some occasions and euthyroid on the other occasions. A magnetic resonance imaging (MRI) revealed a normal pituitary gland. Because her mother also had mild SITSH, genetic analysis was performed and revealed a heterozygous point mutation in TRβ (p.R316C). Previously, the p.R316C had only been found in severe RTH cases with homozygous mutations or with an ectopic thyroid. Her mother with a heterozygous mutation showed variable RTH phenotype on T3 suppression testing. In conclusion, the prevalence of RTHβ might be underestimated and occasional SITSH could also suggest RTHβ. TRβ gene mutation is not always correlated with the RTH phenotype.


Pathogenesis and treatment of myeloma kidney.
The focus of therapy of cast nephropathy, or "myeloma kidney," has been chemotherapy to decrease production of the abnormal monoclonal immunoglobulin and immunoglobulin light chain, known as Bence Jones protein. Little attention has been given to understanding and disrupting the pathophysiologic mechanisms involved in production of intraluminal casts that obstruct and ultimately destroy renal function. Myeloma casts develop in the distal nephron when cast-forming light chains bind to a specific portion of Tamm-Horsfall glycoprotein, secreted by cells of the thick ascending limb of the loop of Henle, to form an insoluble protein complex. A variety of factors including tubule fluid flow rate and concentrations of calcium and sodium chloride in the distal nephron modify the interactions between these proteins and thus influence subsequent clinical renal failure. This review summarizes the latest developments in the pathogenesis and management of cast nephropathy.


FID-based lung MRI at 0.5 T: theoretical considerations and practical implications.
Pulse sequences based on FID signals and projection reconstruction (PR) were investigated for lung MRI at 0.5 T and evaluated for artifacts caused by: (1) k-space mismapping due to either delay or distortion of the readout gradient waveform, (2) cardiac motion and pulsatile flow, and (3) respiratory motion. Nonstructured artifacts were described, simulated, and experimentally confirmed for the first time. Nonstructured artifacts did not impair the demonstration of structures of high signal-to-noise ratio (SNR) but generated quantitative errors in the image intensity analysis over the lung parenchyma. The use of FID-based PR techniques for lung MRI is not justified at 0.5 T.


Radiographic morphology of the ulnar head.
Posteroanterior radiographs of 102 normal wrists were studied to determine the morphological characteristics of the ulnar head associated with the value of ulnar variance. Ulnar variance, ulnar styloid length, ulnar head diameter, ulnar seat inclination, and the distance of ulnar head peak to the distal radioulnar joint were measured together with the third metacarpal length as a reference of the size of the wrist. Moderate correlation was confirmed not only between ulnar variance and ulnar seat inclination but also between ulnar variance and the distance of the ulnar head peak. Furthermore, we found a statistically significant correlation between ulnar variance and ulnar head diameter. The results showed that whole ulnar head configurations are affected by ulnar variance although there are considerable variations.


Relation between Helicobacter pylori infection, thyroid hormone levels and cardiovascular risk factors on blood donors.
The aim of this study was to assess the relationship between Helicobacter pylori (Hp) infection, serum thyroid hormone levels and certain cardiovascular risk factors in normal volunteers. In 110 blood donors (85 men, 25 women, aged 35.6 +/- 9.76) the serum levels of IgG antibodies against Hp were estimated using a sensitive immunoassay. Serum estimation of T3, T4, TSH, FT3, FT4, thyroid (microsomial) autoantibodies, C-Reactive-Protein, a1-acid-glycoprotein, vitamin B12, folic acid, cholesterol, triglycerides, total lipids, HDL, LDL, and antibodies against hepatitis A, was also carried-out. In all subjects a number of clinicoepidemiological parameters including body mass index, smoking habits, educational level, number of siblings and presence of symptoms from the digestive system were carefully recorded. Statistical analyses were performed using the SPSS statistical package. Helicobacter pylori infection was found in 54 subjects (49.1%). On univariate analysis, significant differences between subjects positive and negative for Helicobacter pylori infection were found for FreeT3 (3.11 +/- 0.5 pmol/ vs. 3.42 +/- 0.8 pmol/l, P=0.025), FreeT4 (1.04 +/- 0.2 ng/dl vs. 1.17 +/- 0.3 ng/dl, P=0.025), and thyroid autoanti bodies (23.65 +/- 24 vs. 14.97 +/- 8, P=0.018). Significant differences were also found for Cholesterol (207.8 +/- 39 mg/dl vs. 193.3 +/- 40 md/dl, P=0.05), LDL (133.2 +/- 32 mg/dl vs. 119.6 +/- 40 mg/dl, P=0.05) and folic acid (7.66 +/- 3.7 ng/ml vs. 6.39 +/- 2.5 ng/ml, P=0.038). A significantly positive correlation of Hp infection with age and number of siblings and a negative one with educational level were noticed. No differences concerning the levels of acute phase proteins, vitamin B12, antibodies against hepatitis A, body mass index, and smoking habits were found. On logistic regression analysis, significant differences remained only for thyroid autoantibodies (Odds ratio for titer ?30: 7.8, P=0.012), age (Odds Ratio for those aged >40 years vs those aged <40 years: 3.8, P=0.022) and educational level (Odds ratio for elementary 8.7 and moderate 5.1 vs higher education, P=0.003 and P=0.011 respectively). It is concluded that a relationship exist between Hp infection and the presence of high titers of thyroid autoantibodies in blood donors. There are no indications of the existence of a relationship between Hp infection with thyroid hormone levels, lipid concentrations and other cardiovascular risk factors.


Alkylation of dihydrofullerenes.
The fulleride dianions C(60)(2-) and C(70)(2-) were generated by deprotonation of the corresponding hydrogenated fullerenes, 1,2-C(60)H(2) and 1,2-C(70)H(2). These anions were prepared in the presence of a variety of alkylating agents, and mono- or dialkylated products were obtained. Alkylation was not successful with sulfonate ester alkylating agents. Deprotonation of monoalkylated compounds, followed by second alkylation with a different alkylating agent, produced heterodialkylated compounds. The monoalkyated material was invariably the 1,2-isomers, while the dialkylated materials were generally 1,4-isomers, although some 1,2-isomer was observed in the C(70) context. The major product from alkylation of C(70)(2-) was the 7,23-isomer 13a, a structure where the alkylation took place near the equator of the fullerene cage, rather than at the more strained carbons near the poles.


Lost in time, lonely, and single: reproductive asynchrony and the Allee effect.
Identifying linkages between life-history traits and small population processes is essential to effective multispecies conservation. Reproductive asynchrony, which occurs when individuals are reproductively active for only a portion of the population-level breeding period, may provide one such link. Traditionally, reproductive asynchrony has been considered from evolutionary perspectives as an advantageous bet-hedging strategy in temporally unpredictable environments. Here, we explore the dynamic consequences of reproductive asynchrony as a density-dependent life-history trait. To examine how asynchrony affects population growth rate and extinction risk, we used a general model of reproductive timing to quantify the temporal overlap of opposite-sex individuals and to simulate population dynamics over a range of initial densities and empirical estimates of reproductive asynchrony. We also considered how protandry, a sexually selected life-history strategy that often accompanies asynchrony, modulates the population-level effects of reproductive asynchrony. We found that asynchrony decreases the number of males a female overlaps with, decreases the average probability of mating per male/female pair that does overlap, and leaves some females completely isolated in time. This loss of reproductive potential, which is exacerbated by protandry, reduces population growth rate at low density and can lead to extinction via an Allee effect. Thus reproductive asynchrony and protandry, both of which can be evolutionarily advantageous at higher population densities, may prove detrimental when population density declines.


Theoretical conformational analysis of the opioid delta antagonist H-Tyr-Tic-Phe-OH and the mu agonist H-Tyr-D-Tic-Phe-NH2.
A molecular mechanics study (grid search and energy minimization) of the highly delta receptor-selective delta opioid antagonist H-Tyr-Tic-Phe-OH (TIP; Tic: tetrahydroisoquinoline-3-carboxylic acid) resulted in four low energy conformers with energies within 2 kcal/mol of that of the lowest energy structure. These four conformers contain trans peptide bonds only and represent compact structures showing various patterns of aromatic ring stacking. The centrally located Tic residue imposes several conformational constraints on the N-terminal dipeptide segment; however, the results of molecular dynamics simulations indicated that this tripeptide still shows some structural flexibility, particularly at the Phe3 residue. Analogous studies performed with the structurally related mu receptor-selective mu agonist H-Tyr-D-Tic-Phe-NH2 resulted in low energy structures that were also compact but showed patterns of ring stacking different from those obtained with TIP. Superimposition of low energy conformers of TIP and H-Tyr-D-Tic-Phe-NH2 revealed that the Phe3 residues of the L-Tic- and the D-Tic peptide were always located on opposite sides of the plane defined by the Tic residue, thus providing an explanation for the distinct activity profiles of the two compounds in structural terms. Attempts to demonstrate spatial overlap between the pharmacophoric moieties of low energy conformers of TIP and the nonpeptide delta antagonist naltrindole were made by superimposing either the Tyr1 and Tic2 aromatic rings and the N-terminal amino group or the Tyr1 and Phe3 aromatic rings and the N-terminal amino group of the peptide with the corresponding aromatic rings and nitrogen atom in the alkaloid structure.(ABSTRACT TRUNCATED AT 250 WORDS)


Time course of cytokine, corticosterone, and tissue injury responses in mice during heat strain recovery.
Elevated circulating cytokines are observed in heatstroke patients, suggesting a role for these substances in the pathophysiological responses of this syndrome. Typically, cytokines are determined at end-stage heatstroke such that changes throughout progression of the syndrome are poorly understood. We hypothesized that the cytokine milieu changes during heatstroke progression, correlating with thermoregulatory, hemodynamic, and tissue injury responses to heat exposure in the mouse. We determined plasma IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-gamma, macrophage inflammatory protein-1alpha, TNF-alpha, corticosterone, glucose, hematocrit, and tissue injury during 24 h of recovery. Mice were exposed to ambient temperature of 39.5 +/- 0.2 degrees C, without food and water, until maximum core temperature (T(c,Max)) of 42.7 degrees C was attained. During recovery, mice displayed hypothermia (29.3 +/- 0.4 degrees C) and a feverlike elevation at 24 h (control = 36.2 +/- 0.3 degrees C vs. heat stressed = 37.8 +/- 0.3 degrees C). Dehydration ( approximately 10%) and hypoglycemia ( approximately 65-75% reduction) occurred from T(c,Max) to hypothermia. IL-1alpha, IL-2, IL-4, IL-12p70, IFN-gamma, TNF-alpha, and macrophage inflammatory protein-1alpha were undetectable. IL-12p40 was elevated at T(c,Max), whereas IL-1beta, IL-6, and IL-10 inversely correlated with core temperature, showing maximum production at hypothermia. IL-6 was elevated, whereas IL-12p40 levels were decreased below baseline at 24 h. Corticosterone positively correlated with IL-6, increasing from T(c,Max) to hypothermia, with recovery to baseline by 24 h. Tissue lesions were observed in duodenum, spleen, and kidney at T(c,Max), hypothermia, and 24 h, respectively. These data suggest that the cytokine milieu changes during heat strain recovery with similarities between findings in mice and those described for human heatstroke, supporting the application of our model to the study of cytokine responses in vivo.


Can digitalization and low-carbonization progress in harmony? Evidence from Chinese cities.
Achieving high-quality development of the city requires actively promoting coordinated digitalization and low-carbon development. Previous studies have focused on the unidirectional impact of urban digitalization on low-carbonization and there is a lack of research on their interactions. This study uses the generalized spatial three-stage least squares method and the spatial simultaneous equation to investigate the endogenous interactions between urban digitalization and low-carbonization. The properties of the spatiotemporal evolution are then examined using linked coordination degree models, kernel density, and spatial statistical approaches. Finally, using the spatial panel metering model, this study empirically investigates the motivations behind the synergistic advancement of digitalization and low-carbonization. The results show that: (1) There is an endogenous interaction between urban digitalization and low-carbonization and that this interaction pattern is closely linked to geographical proximity. (2) In general, both urban digitalization and low-carbonization have a positive spatial impact and a negative spatial interaction, and their coordination levels have a significant spatial impact. (3) Throughout the research period, the coordination degree of urban digitalization and low carbonization continued to increase, showing a positive spatial correlation and a balanced development trend. (4) Economic development, industrial structure, and human capital accumulation are vital internal drivers of the synergistic advancement of urban digitalization and low carbonization. Government capacities and technological innovations are key external factors that contribute to the synergistic advancement of urban digitalization and low-carbonization. Overall, the paper is essential not only to deepen understanding of the relationship between urban digitalization and low-carbonization but also to formulate policies for their coordinated development.


[Endoscopic palliation of inoperable hilar biliary carcinoma with self-expanding metal stents].
Prosthetic palliation of patients with malignant hilar stenoses shows particular difficulties, especially in advanced lesions. This is a prospective report of the efficacy of endoscopically inserted single metal stent for complex malignant biliary hilar obstruction. Sixty-one consecutive patients were recruited. Contrast injection was deliberately limited to the distal end of the malignant tumor stenosis. A single metal stent was inserted across the stricture into the duct that was technically easiest for the drainage. Successful stent insertion was achieved in 59 of 61 (96.7%) patients. In 3 (4.9%) cases stent malfunction occurred. Successful drainage was achieved in 59 (96.7%) patients and complete resolution of jaundice was achieved in 86% of cases. Early complications included 3 (4.9%) cases of cholangitis and 2 (3.2%) cases of stent occlusion. Late occlusion of the stent occurred in 14 patients (22.9%), including 10 (16.3%) cases of cholangitis and 1 case of liver abscess. Median stent patency was 169 days. Median patient survival was 140 days. Metal stent insertion is safe, feasible, and achieves adequate drainage in the great majority of patients with non-resectable hilar cholangiocarcinoma.


Refining the metabolisable energy value of field beans for turkeys.
1. This study examined the feeding value of ten UK grown field bean (Vicia faba L. var. minor) cultivar samples from the same harvest year on nitrogen corrected apparent metabolisable energy (AMEn) and nutrient retention coefficients when fed to young female turkeys.2. A balancer feed (BF) was formulated to contain 12.39 MJ/kg ME and 269 g/kg crude protein. Ten nutritionally complete, mash diets were prepared by mixing 200 g/kg of each ground field bean cultivar with 800 g/kg of the BF, totalling eleven diets. Diets were fed to female BUT Premium turkeys from 40 to 50 d of age. Each diet was fed to eight raised floor pens, housing two birds, following randomisation. The AMEn was determined by the total collection technique over the last 4 d of the study. Relationships were examined between AMEn, chemical composition and quality variables of the field bean samples.3. The overall determined AMEn value of the beans ranged from 7.72 MJ/kg DM to 9.87 MJ/kg DM, giving an average AMEn of 8.80 MJ/kg DM (P < 0.05). The soluble non-starch polysaccharide (NSP) content of the beans negatively correlated with their determined AMEn (r = -0.730; P < 0.05). Bean flour lightness-darkness degree (L*) correlated positively with the AMEn (r = -0.643; P < 0.05)4. A positive correlation was observed between the degree of yellowness-blueness of bean flour and condensed tannins content (r = 0.696; P < 0.05). Step-wise regression indicated that soluble NSP + L* of field beans provided explanatory variables suitable for estimating the AMEn value for turkeys (r2 = 0.737; P < 0.05).


"Si Dios Quiere": Fatalismo and use of mental health services among Latinos with a history of depression.
Latinos are less likely to seek professional mental health care than other groups in the United States. While fatalismo has long been hypothesized to be responsible for this behavior, there is little evidence on this assumption. Using an adapted version of the Behavioral Model of Health Service Use (BMHSU), and a nationally representative sample, this study examined the association between fatalismo and mental health service use among Latinos with a history of depression. Participants (n = 703) were drawn from the 2007 Pew Hispanic Healthcare survey. Results showed that fatalismo was significantly associated with the use of psychiatric care, even after controlling for traditional deterrents of health care access and utilization. The findings underscore the importance of fatalismo in predicting Latinos' use of psychiatric care. Implications for practice are discussed.


Paravertebral Analgesia in Video-Assisted Thoracic Surgery: A New Hybrid Technique of Catheter Placement for Continuous Anesthetic Infusion.
Advantages of paravertebral analgesia in thoracotomy include the absence of morphine side effects and the lack of contraindications. We introduce a new technique for paravertebral catheter placement during video-assisted thoracic surgery. The catheter is placed in the same intercostal space as the camera port. Anesthetic is injected to reach the parietal pleura. The catheter is inserted through the needle and pushed until the paravertebral space is reached. Postoperative analgesia is performed by a continuous infusion of local anesthetics. Our technique is safe and easy to perform and avoids opioid use. It works differently from intercostal analgesia and paravertebral blocks.


In situ hybridization of putative somatostatin mRNA in the brain of electric gymnotiform fish.
The distribution of somatostatin mRNA in the brain of Apteronotus leptorhynchus, a weakly electric gymnotiform fish, has been mapped by employing in situ hybridization with an oligodeoxynucleotide probe corresponding to nucleotides 1-26 of catfish somatostatin mRNA; this probe was end-labelled with digoxigenin. Most labelled cell groups were found in the telencephalon, followed by the diencephalon. This distribution is in good agreement with previous immunohistochemical investigations. In the complex of the diencephalic central-posterior/prepacemaker nucleus, a cluster of neurons controlling electrocommunicatory behavior, somatostatin mRNA could be detected only in lateral aspects, although many medial cells also stain positively with immunohistochemical techniques. This difference may be related to the growth of these neurons during adulthood.


Analysis of Variance Models with Stochastic Group Weights.
The analysis of variance (ANOVA) is still one of the most widely used statistical methods in the social sciences. This article is about stochastic group weights in ANOVA models - a neglected aspect in the literature. Stochastic group weights are present whenever the experimenter does not determine the exact group sizes before conducting the experiment. We show that classic ANOVA tests based on estimated marginal means can have an inflated type I error rate when stochastic group weights are not taken into account, even in randomized experiments. We propose two new ways to incorporate stochastic group weights in the tests of average effects - one based on the general linear model and one based on multigroup structural equation models (SEMs). We show in simulation studies that our methods have nominal type I error rates in experiments with stochastic group weights while classic approaches show an inflated type I error rate. The SEM approach can additionally deal with heteroscedastic residual variances and latent variables. An easy-to-use software package with graphical user interface is provided.


The Burdens and Uncertainties of Doing What One Should Do.
Despite FDA approval of drugs to reduce the risk of breast cancer in women at increased risk, uptake of these drugs has been poor despite the publication of numerous studies that demonstrate both their effectives and safety. National organizations have made recommendations for their use, but both physicians and their patients do not fully understand either breast cancer risk factors or risk assessment or the indications for using risk-reducing agents. Histologically predisposing conditions, such as ductal or lobular atypia and lobular carcinoma in situ, impart particularly high risks of developing subsequent invasive breast cancer. Resources should be committed to both provider and patient education to reduce the risk of breast cancer in women who are at increased risk. Cancer Prev Res; 10(8); 431-3. ©2017 AACR.


Intravenous heparin started within the first 3 hours after onset of symptoms as a treatment for acute nonlacunar hemispheric cerebral infarctions.
Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms. The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 x control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke. A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9% versus 28.6%; P=0.025). In addition, in the same group, there were fewer deaths (16.8% versus 21.9%; P=0.189), more symptomatic brain hemorrhages (6.2% versus 1.4%; P=0.008), and more major extracerebral bleedings (2.9% versus 1.4%; P=0.491). Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.


Subjective and objective measures of sleepiness: effect of benzodiazepine and caffeine on their relationship.
As part of a larger project on the effects of benzodiazepine and caffeine on daytime sleepiness, performance and mood, this study examined the relationship among the Multiple Sleep Latency Test, lapses during a tapping task, a Visual Analog Scale, and the Stanford Sleepiness scale. Subjects were 80 male, adult nonsmokers aged 20.3 +/- 2.7 years. The Multiple Sleep Latency Test, Stanford Sleepiness Scale, and the Visual Analog Scale were obtained at two-hour intervals beginning at 0700 h and ending at 1700 h. The tapping task (lapses) was administered each day at 0600 h, 1000 h, and 1400 h. A lapse was a 3-s or greater pause between taps. Correlations between the Multiple Sleep Latency Test and subjective (Visual Analog Scale and the Stanford Sleepiness Scale) measures were significant at 0600 h, but became nonsignificant as the day progressed. Correlations between lapses and the two subjective measures were generally nonsignificant. The two objective measures were significantly correlated in the total group but not in all treatment groups. The subjective measures were significantly correlated in the total sample and in each treatment group. This study reaffirms the importance of time of day when measuring sleepiness, and suggests that subjective and objective measures may measure different aspects of sleepiness.


Red clover Trifolium pratense L. phytoestrogens: UV-B radiation increases isoflavone yield, and postharvest drying methods change the glucoside conjugate profiles.
Isoflavone extracts of red clover Trifolium pratense L. (cv. Pawera) with dissimilar glucoside conjugate profiles were obtained by employing different postharvest drying methods. The most prominent isoflavones found were formononetin and biochanin A and their corresponding glucosides and malonyl glucoside esters. Postharvest freeze drying inhibited the conversion of the glycosides to the aglycones, while vacuum drying allowed for maximum conversion of the glycosides to their corresponding aglycones. Air drying produced a low level of the aglycones formononetin and biochanin A, and oven drying promoted decarboxylation of the malonyl glucosides to the acetyl glucosides. Exposure to enhanced UV-B radiation resulted in an increase in total formononetin and biochanin A isoflavone levels, indicating that harvest during a period of high ambient UV-B radiation may be appropriate for maximum yield. The levels of caffeic acid and flavonols also increased by about 40 and 250%, respectively, on exposure to enhanced UV-B radiation.


The cleavage specificity of RNase III.
We determined sites in lambda cII mRNA that are cleaved by RNase III in the presence of lambda OOP antisense RNA, using a series of OOP RNAs with different internal deletions. In OOP RNA-cII mRNA structures containing a potential region of continuous double-stranded RNA bounded by a non-complementary unpaired region, RNase III cleaved the cII mRNA at one or more preferred sites located 10 to 14 bases from the 3'-end of the region of continuous complementarity. Cleavage patterns were almost identical when the presumptive structure was the same continuously double-stranded region followed by a single-stranded bulge and a second short region of base pairing. The sequences of the new cleavage sites show generally good agreement with a consensus sequence derived from thirty-five previously determined cleavage sequences. In contrast, four 'non-sites' at which cleavage is never observed show poor agreement with this consensus sequence. We conclude that RNase III specificity is determined both by the distance from the end of continuous pairing and by nucleotide sequence features within the region of pairing.


The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance.
Immune responses must be tightly regulated to avoid hyporesponsiveness on one hand or excessive inflammation and the development of autoimmunity (hyperresponsiveness) on the other hand. This balance is attained through the throttling of activating signals by inhibitory signals that ideally leads to an adequate immune response against an invader without excessive and extended inflammatory signals that promote the development of autoimmunity. The CD94/NKG2 family of receptors is composed of members with activating or inhibitory potential. These receptors are expressed predominantly on NK cells and a subset of CD8+ T cells, and they have been shown to play an important role in regulating responses against infected and tumorigenic cells. In this review, we discuss the current knowledge about this family of receptors, including ligand and receptor interaction, signaling, membrane dynamics, regulation of gene expression and their roles in disease regulation, infections, and cancer, and bone marrow transplantation.


Effect of ganglionic blockade with trimethaphan on corticosteroid responses to metoclopramide in rhesus monkeys.
In order to investigate whether metoclopramide stimulates 18-hydroxycorticosterone and aldosterone production directly by way of the autonomic nervous system, we have examined the effects of ganglionic blockade with trimethaphan on the responses to metoclopramide (200 micrograms/kg) in rhesus monkeys. Trimethaphan, infused at a rate (200 micrograms/kg/min) which significantly decreased mean arterial pressure from 122 +/- 7 to 62 +/- 4 mmHg, did not alter the peak plasma 18-OHB and aldosterone responses to metoclopramide. These results suggest that 18-hydroxycorticosterone and aldosterone responses to metoclopramide occur independently of adrenergic neuronal input.


Structure of the major oxidative damage 7,8-dihydro-8-oxoguanine presented into a catalytically competent DNA glycosylase.
If left unrepaired, the major oxidative DNA lesion 7,8-dihydro-8-oxoguanine (oxoG) promotes G-to-T transversions by favorably adopting a syn conformation and base pairing with dATP during replication. The human oxoG DNA glycosylase hOGG1 senses and removes oxoG amid millions-fold excess of guanine, thereby counteracting the genotoxic effects of the major oxidative damage. Crystal structures of hOGG1 in complex with oxoG-containing DNA have provided key insights into the lesion recognition and catalysis mechanisms of the enzyme. These lesion-recognition complex (LRC) structures typically involve a catalytically inactive hOGG1 mutant, where one of the catalytic-site amino acid residues is mutated to prevent the cleavage of oxoG. The use of a catalytically incompetent hOGG1 mutant has thus precluded understanding of unscathed interactions between oxoG and hOGG1 catalytic site as well as interactions among catalytic-site amino acid residues. As an orthogonal approach to visualize such interactions, we have co-crystallized a catalytically competent hOGG1 bound to 2'-fluoro-oxodG-containing DNA, a transition state destabilizing inhibitor that binds hOGG1 but is not processed by the enzyme. In this fluorinated lesion-recognition complex (FLRC), the 8-oxo moiety of oxoG is recognized by Gly42 and the Watson-Crick edge of oxoG is contacted by Gln315 and Pro266. The previously observed salt bridge between Lys249 and Cys253 is lacking in the FLRC, suggesting Lys249 is primed by Cys253 and poised for nucleophilic attack on C1' of oxodG. Overall, hOGG1 FLRC marks the first structure of oxoG presented into an intact catalytic site of hOGG1 and provides complementary insights into the glycosylase mechanisms of the enzyme.


Force attractor in confined comminution of granular materials.
We reveal a novel attractor in the space of contact forces that bounds the behavior of granular materials during confined comminution. The attractor is reached asymptotically as the porosity reduces and the grain size distribution attains an ultimate power law scaling. The ultimate distribution of the contact forces follows a clear log-normal distribution, distinctively different from previous observations in uncrushable systems. Supporting evidence comes both from comprehensive discrete element simulations and a theoretical Apollonian model.


The effects of priming in a cued dot-probe task on appearance-related attentional biases in women.
The dot-probe task (DPT) is a reaction time measure of attentional bias. Research using this task has found inconsistent patterns of appearance-related attentional biases in women. This study examined the effects of a novel priming variation of the DPT, which incorporated additional cues into each trial of the task, on measurement of such biases. The study also examined associations between these biases and body image, a component of eating disorder symptomatology. A convenience sample of women from the general community (N = 103) completed body image measures online and attended a laboratory session to complete one of four DPTs: (1) an appearance-cued DPT containing images of thin-ideal models between each trial; (2) neutral-cued DPT containing images of forests; (3) time-delayed DPT controlling for time in place of an image; or (4) typical DPT containing only word stimuli. Women who completed the appearance-cued DPT demonstrated a stronger attentional bias for positive, but not negative, appearance words than women who completed the other DPT versions. Furthermore, for the appearance-cued and time-delayed DPTs, this bias correlated with poorer body image across several indicators (appearance evaluation, body dissatisfaction, self-evaluative salience of appearance, and state body satisfaction). Although it was unexpected that no attentional bias for negative-appearance words was found, the attentional bias for positive-appearance words may suggest that effects were driven by the ego-threat of positive-appearance words. Further research is warranted to determine whether such biases contribute to and maintain body image disturbance and disordered eating.


Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs). However, inconsistent evidence has been obtained regarding the efficacy of zinc supplementation in the context of malaria prevention. This systematic review was implemented to survey the existing literature to determine the effects of the daily oral administration of zinc, either alone or in combination with other nutrient supplements, on the risk of malaria parasitaemia. The systematic review was prospectively registered in the PROSPERO database CRD42023424345 and followed PRISMA protocols. A comprehensive search was conducted across multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar, from their inception until 6 May 2023. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). The effect sizes, represented as risk ratios (RRs) with 95% confidence intervals (CIs), were standardised by transforming them into log RRs and then pooling them using a fixed-effects or random-effects model depending on the heterogeneity across studies. Comparisons were made between individuals who received zinc alone or zinc in combination with other micronutrient supplements and those who did not receive zinc. A total of 1339 articles were identified through the database searches, and after the screening and selection process, 10 studies were included in the final synthesis. The meta-analysis revealed that zinc supplementation alone did not significantly affect the risk of malaria parasitaemia compared with placebo (p = 0.30, log RR = 0.05, 95% CI: -0.05-0.15, I2 = 0.00%, with 566 malaria cases in the zinc intake group and 521 malaria cases in the placebo group). However, the analysis demonstrated a borderline significant effect of zinc supplementation in combination with other micronutrients on the risk of malaria parasitaemia compared with placebo (p = 0.05, log RR = 1.31, 95% CI: 0.03-2.59, I2 = 99.22%, with 8904 malaria cases in the zinc intake group and 522 malaria cases in the placebo group). The findings of this systematic review indicate that zinc supplementation, either alone or combined with the supplementation of other micronutrients such as vitamin A, iron, or multiple nutrients, does not significantly alter the risk of malaria parasitaemia. Further research with larger sample sizes is warranted to explore the potential effects of multi-nutrient supplementation and to identify more specific micronutrients and additional factors associated with the risk of malaria, rather than just zinc alone, among individuals in different malaria-endemic areas.


Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.
Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.


Phenolic Responses to Esca-Associated Fungi in Differently Decayed Grapevine Woods from Different Trunk Parts of 'Cabernet Sauvignon'.
Alterations in phenolic contents were studied in Esca symptomatic (Sym) and asymptomatic (Asym) vines of 'Cabernet Sauvignon' based on wood conditions (healthy, HLT; necrotic, Nec; and rotten, Rot) and vine parts (head, trunk, and rootstock). In Asym vines, only Alternaria alternate was identified in Nec wood, while the HLT wood of Sym vines was colonized by Botryospaeriaceae sp. and Aureobasidium pullulans, Nec wood by Fomitiporia mediterranea, and Rot wood by Fomitiporia mediterranea and Phaeomoniella chlamydospora. Esca infection caused a significant accumulation of gallic acid, total flavanols, stilbenes (STB), and total analyzed phenolics (TAP) in all studied woods, especially in Nec wood. In Asym vines, TAP in the head increased with necrosis, but in Sym it decreased, while TAP in the trunk and rootstock of Sym showed an opposite response. The significantly highest contents of procyanidins (Pcys), catechin, epicatechin, epicatechin gallates, and Pcys dimers and tetramers were measured in HLT wood in the head and in Nec wood in the trunk of Sym vines. The significant increase of STB content was not caused only by Esca infection in HLT wood but also by necrosis in Asym vines, especially of ε-viniferin glucoside, resveratrol glycosides, and astringin. The obtained results suggest that the alteration in phenolics differed not only due to Esca infection but also due to the wood conditions and vine part, which might reflect the impact of the duration of the presence of the pathogen in different parts of the vine.


Leu-22: a preferential marker for T-lymphocytes in paraffin sections. Staining profile in T- and B-cell lymphomas, Hodgkin's disease, other lymphoproliferative disorders, myeloproliferative diseases, and various neoplastic processes.
Monoclonal antibody Leu-22 represents an effective reagent for detection of neoplastic and nonneoplastic T-cells in paraffin sections of routinely processed tissues (242 specimens evaluated). In nonneoplastic tissues, immunoreactivity was localized mainly to lymphoid cells corresponding to a T-cell distribution. Immunoreactivity in lymphoid neoplasms, however, was preferentially, but not exclusively, limited to T-cell populations. Fifty-four of 60 T-cell neoplasms (90%) of various histologic types were Leu-22 positive. The pattern of immunoreactivity consisted mainly of membrane staining, with focal weak cytoplasmic positivity. Twenty-five of 67 B-cell neoplasms (37%) were also Leu-22 positive, with low-grade lymphomas (well/moderately well-differentiated lymphocytic types) representing most immunoreactive cases. In Hodgkin's disease, although most small lymphoid cells were Leu-22 positive, only rare Reed-Sternberg cells were immunoreactive. In all cases, histiocytes and myeloid cells exhibited variable immunoreactivity. The epitope identified by Leu-22 was detectable in formalin- and B5-fixed tissues but apparently was denatured after fixation in Zenker's-acetic acid solution used for bone marrow biopsies. Evaluation of a wide variety of nonhematopoietic neoplasms (64 total) revealed diffuse cytoplasmic staining in a few cases. However, membrane staining, typically noted for lymphoid cells, was not observed. Leu-22 potentially represents a useful marker for lymphoid cells, preferentially of T-cell origin, with optimal applicability as part of a panel that includes an effective pan-B-cell marker.