LIF spectroscopy of stained malignant breast tissues.
We employ laser induced fluorescence (LIF) spectroscopy to discriminate between normal and cancerous human breast (in-vitro) tissues. LIF signals are usually enhanced by the exogenous agents such as Rhodamine 6G (Rd6G) and Coumarin 7 (C7). Although we observe fluorescence emissions in both fluorophores, Rd6G-stained tissues give notable spectral red shift in practice. The latter is a function of dye concentration embedded in tissues. We find that such red shifts have a strong dependence on the dye concentration in bare, in stained healthy, and in malignant breast tissues, signifying variations in tubular abundances. In fact, the heterogeneity of cancerous tissues is more prominent mainly due to their notable tubular densities- which can provide numerous micro-cavities to house more dye molecules. We show that this can be used to discriminate between the healthy and unhealthy specimens in different biological scaffolds of ordered (healthy) and disordered (cancerous) tissues. It is demonstrated that the quenching process of fluorophore' molecules slows down in the neoplastic tumors according to the micro-partitioning, too.


Promotion of metastases by tumor necrosis factor in rats bearing Dunning R3327 MAT-LyLu prostatic cancer.
We examined the effects of recombinant human tumor necrosis factor (rTNF) on highly metastatic rat prostatic cancer, Dunning R3327 MAT-LyLu, in vivo. It seemed that the inhibition of tumor growth needed more than 5 x 10(5) units of rTNF and this dose was near the lethal dose. Concerning the effect of rTNF on metastasis, we found that the metastasis to lung was promoted by 1 x 10(5) units of rTNF and the promotion of metastasis was restricted by indomethacin. Although MAT-LyLu cells were producing a significant amount of prostaglandin E2, rTNF did not enhance the production. We therefore consider that the promotion of metastasis was not mediated by prostaglandin E2 from MAT-LyLu cells but was mediated by other very complicated conditions. Further studies are necessary to resolve the mechanisms.


Rapid Detection of Anti-SARS-CoV-2 Antibody Using a Selenium Nanoparticle-Based Lateral Flow Immunoassay.
Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is highly transmissible. Early and rapid testing is necessary to effectively prevent and control the outbreak. Detection of SARS-CoV-2 antibodies with lateral flow immunoassay can achieve this goal. In this study, SARS-CoV-2 nucleoprotein (NP) was expressed and purified. We used the selenium nanoparticle as the labeling probe coupled with the NP to prepare an antibody (IgM and IgG) detection kit. The detection limit, cross reaction, sensitivity and specificity of the kit is verified. Separate detection of IgM and IgG, such as in this assay, was performed in order to reduce mutual interference and improve the accuracy of the test results.The final purity of NP was 91.83%. Selenium nanoparticle and NP successfully combined with stable effect. The LOD of the kit was 20 ng/mL for anti-NP IgG and 60 ng/mL for anti-NP IgM, respectively. The kit does not cross reaction with RF. The sensitivity of the kit was 94.74% and the specificity was 96.23%. The assay kit does not require any special device for reading the results and the readout is a simple color change that can be evaluated with the naked eye. This kit is suitable for rapid and real-time detection of the SARS-CoV-2 antibody IgG and IgM.


Intraorbital arteriovenous malformation: case report.
An intraorbital arteriovenous malformation became symptomatic without exophthalmos but with chemosis and bruit of the left eye. The patient underwent only surgical treatment. The orbital rim was removed through a fronto-orbital approach. The chemosis was corrected and postoperative magnetic resonance imaging and angiography confirmed complete removal of the malformation. Histopathological examination disclosed an arteriovenous malformation in the extrabulbar fatty tissue without invasion of the extraocular muscles or optic nerve. The differences between various types of intraorbital malformations are discussed.


Different Viewpoints: International Perspectives on Newborn Screening.
Newborn blood-spot screening to detect potentially treatable disorders is widely practiced across the globe. However, there are great variations in practice, both in terms of disorders covered, screening technologies, disease definition, information provision, parental informed consent, and storage and disposal of residual specimens, partly reflecting the degree to which screening is the subject of explicit legislation (and thus public and media pressure) or is embedded in a general health care system and managed at an executive level. It is generally accepted that disorders to be screened for should comply with the ten Wilson and Jungner criteria, but the way that compliance is assessed ranges from broadly-based opinion surveys to detailed analysis of quantitative data. Consequently, even countries with comparable levels of economic development and health care show large differences in the number of disorders screened for. There are several areas on which there are no generally accepted guidelines: how should parents be informed about screening and to what extent should they be encouraged to regard screening as an option to choose to refuse? Is DNA mutation analysis acceptable as part of a screening protocol? How soon should the blood samples be destroyed once screening has been completed? As technology advances and the potential scope of screening expands at both the metabolite and genome level, challenging policy issues will have to be faced.


Mass Killings in the United States from 2006 to 2013: Social Contagion or Random Clusters?
In line with previous research on suicide and social contagion, there has been widespread speculation that mass killings-which often involve suicidal offenders-are socially contagious for up to 14 days. This study tested these claims by making comparisons (i) between observed chronological clusters of mass killings in the United States from 2006 to 2013 and clusters in 500 simulations containing 116,000 randomly generated dates, and then (ii) between observed mass killings receiving varying levels of public attention. No evidence of short-term contagion was found, although longer term copycat effects may exist. Further scholarly and policy implications are discussed.


Effects of medium- and long-chain fatty acids on whole body leucine and glucose kinetics in man.
Elevation of plasma concentrations of nonesterified fatty acids (NEFA) has been reported to result in protein sparing and in impaired insulin-mediated glucose metabolism. To assess the influence of the chain length of fatty acids on these effects, medium-chain (MC) and long-chain (LC) fatty acid-containing lipid emulsions (2 mg/kg/min each) combined with heparin were administered during 390 minutes to 25 healthy overnight-fasted male subjects. Whole body leucine flux (a parameter of whole body protein breakdown) decreased during MC triglycerides (MCT) by 20% (P <.005). Irreversible leucine catabolism (oxidation of [1-(13)C]-leucine) decreased during LC triglycerides (LCT) by 40% (P <.01) but not during MCT when compared to controls receiving glycerol infusions. MCT administration resulted in a marked (52 %, P <.001) decrease of alpha-ketoisocaproate (alpha-KIC) concentration, suggesting diminished leucine transamination and decreased leucine nonoxidative disappearance (P <.015). Hyperinsulinemia (30 to 40 microU/mL, euglycemic clamping) resulted in decreased leucine flux and oxidation during both lipid infusions, particularly during MCT. The increase in glucose disappearance during hyperinsulinemia in subjects receiving MCT or LCT was less than in controls, and endogenous glucose production measured by 6,6-D(2)-glucose infusions was less suppressed (P <.01). Thus, elevation of plasma LC fatty acids (but not of MC fatty acids) results in decreased leucine oxidation (protein catabolism). This protein-sparing effect of LCT appears to be dissociated from fatty acid effects on glucose metabolism; both MCT and LCT diminished insulin's ability to increase glucose disappearance and to decrease hepatic glucose production.


The effect of physical and emotional partner violence exerted during pregnancy on prenatal attachment and depression levels in pregnant women.
Exposure of pregnant women to physical and emotional violence during pregnancy adversely affects the health of the mother and the fetus. This study aimed to assess the effects of emotional and physical partner violence on prenatal attachment and depression levels in pregnant women. Five-hundred and ten pregnant women in the second and third trimesters were included in the study. A personal information form, the Epidemiological Research Center Depression Scale, and the prenatal attachment inventory (PAI) were used for data collection. Although 7.5% of the pregnant women were exposed to physical partner violence during pregnancy, 24.3% were exposed to emotional partner violence. Depression was observed in 86.9% of the pregnant women, whereas the mean PAI score was 37.29 ± 10.504. There was a statistically significant relationship between the pregnant women's exposure to physical (p = .046) and emotional partner violence (p < .001) and depression. In this study, it was determined that pregnant women's exposure to emotional partner violence poses a risk for depression during pregnancy (p < .002; odds ratio = .143). As professionals working with pregnant women, obstetricians and maternity nurses should inquire about the exposure of pregnant women to partner violence during antenatal follow-ups.


Imogene King's conceptual framework: a proposed model for continuing nursing education.
This paper presents a proposed model for continuing nursing education based on Imogene King's conceptual framework. The rationale for using King's conceptual framework as the foundation underlying this proposed model is three-fold: the concepts--social systems, health, perception, and interpersonal relationships--are relevant in every nursing situation; the interacting levels of operation--individuals, groups, and society--depict a reciprocal relationship between human behaviour and the environment; and the triad of elements--continuing nursing education, nursing practice, and nursing research--are interrelated in the nursing profession. The authors contend that this approach to continuing nursing education is beneficial to participating nurses, the health care consumer, and to the advancement of the nursing profession. Based on its simplicity and flexibility, the proposed intra-systems model described in this article is useful as a systematic guide for continuing nursing education. The authors believe that this proposed model provides an approach for stimulating continued learning, for establishing innovative foundations for nursing practice, and for generating inquiry through research. Utilizing this approach in maintaining the educational standards for professional practice will promote change for the advancement of the nursing profession.


In-season training periodization of professional soccer players.
The aim of this study was to quantify the seasonal perceived respiratory and muscular training loads (i.e., sRPEres-TL and sRPEmus-TL) completed by elite-oriented young professional soccer players. Twenty-four players (20.3 ± 2.0 years) belonging to the same reserve team of a Spanish La Liga club participated in this study. Only the players that were available to train for a whole week with the team and also to play the weekly game were considered: Starters, players that participated in the match for at least 45 min and Non-Starters, players that did not participate or played less than 45 minutes in the match. The competitive period was analysed after the division into 5x6-8 week blocks and 35x1 week microcycles. Data were also analysed with respect to number of days before the immediate match. Weekly TL variation across the in-season blocks was trivial-small for both groups except between Block 2 and Block 3 (ES= moderate). Substantial TL differences (ES= small-very likely) were found between training days, the TL pattern being a progressive increase up to MD-3 followed by a decrease until MD-1. Except for the match, sRPEres-/sRPEmus-TL was very similar between Starters and Non-Starters. In summary, perceived TL across the season displayed limited variation. Coaches periodized training contents to attain the highest weekly TL 72 hours before the match to progressively unload the players between MD-3 and the match day. The data revealed that the TL arising from the weekly game was solely responsible for the observed higher weekly TL of Starters in comparison with Non-Starters.


Retinopathy of prematurity: progress report.
For the time being, risk of ROP seems inexorably linked to survival of extremely low birth weight prematures, whose embryonic retinas develop in an abnormal and fluctuating environment. Incidence and severity may be reduced by stabilizing ventilation, oxygenation, and perfusion, moderating light exposure, and providing normal levels of vitamin E. Progression of stage 3 retinopathy may sometimes be arrested by cryotherapy. In the future, antioxidants or other pharmacologic agents may be developed to provide a greater margin of safety. In the meantime, the eyes of prematures must be examined and those with ROP will need specialized ophthalmologic care.


Quantifying ecosystem services supply and demand shortfalls and mismatches for management optimisation.
Research on ecosystem services (ESs) has increased substantially in recent decades, but the findings have been slow to affect actual management, perhaps because most studies to date have neglected ESs supply and demand coupling mechanisms. Human reliance on ESs is due to the capacity of the landscape to supply services, but also to a societal need for these services. Sustainable land management requires supply and demand mismatches to be reconciled and the needs of different stakeholders to be balanced. Explicit spatial mapping of ESs supply and demand associated with land use changes can provide relevant insights for enhancing land management in urban areas. The emphasis is now shifting to enhancing sustainable land use, to ensure that supply meets or exceeds demand. In this study, a comprehensive framework comprising four core steps for quantifying ESs supply and demand changes associated with land use changes was developed and applied in a case study on Shanghai municipality, on the basis of environmental quality standards and policy goals. The balance thresholds of ESs supply and demand were derived by regression analysis between ESs and land use/land cover types. The results revealed large spatial heterogeneity in supply and demand for four key ESs tested: carbon sequestration, water retention, particulate (PM10) removal and recreation. Carbon sequestration, water retention and recreation services all showed major shortfalls in supply that changed dramatically with urban land use change. This is valuable empirical evidence and has timely policy implications for management in a rapid urbanising world.


Resequencing and Signatures of Selective Scans Point to Candidate Genetic Variants for Hair Length Traits in Long-Haired and Normal-Haired Tianzhu White Yak.
Tianzhu white yak is a rare local yak breed with a pure white coat in China. In recent years, breeders have discovered long-haired individuals characterized by long hair on the forehead in the Tianzhu white yak, and the length and density of the hair on these two parts of the body are higher than that of the normal Tianzhu white yak. To elucidate the genetic mechanism of hair length in Tianzhu white yak, we re-sequence the whole genome of long-haired Tianzhu White yak (LTWY) (n = 10) and normal Tianzhu White yak (NTWY) (n = 10). Then, fixation index (F ST), θπ ratio, cross-population composite likelihood ratio (XP-CLR), integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and one composite method, the de-correlated composite of multiple signals (DCMS) were performed to discover the loci and genes related to long-haired traits. Based on five single methods, we found two hotspots of 0.2 and 1.1 MB in length on chromosome 6, annotating two (FGF5, CFAP299) and four genes (ATP8A1, SLC30A9, SHISA3, TMEM33), respectively. Function enrichment analysis of genes in two hotspots revealed Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway were involved in the process of hair length differences. Besides, the DCMS method further found that four genes (ACOXL, PDPK1, MAGEL2, CDH1) were associated with hair follicle development. Henceforth, our work provides novel genetic insights into the mechanisms of hair growth in the LTWY.


Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cis-trans interconversions.
The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers' function. The molecular system of N-methylacetamide · 2H2O is complex enough to reveal energetics of the cis-trans isomerization at coupled cluster single-double and coupled cluster single-double and perturbative triple [CCSD(T)] levels of theory. The cis-trans isomerization cannot be oversimplified by a rotation along ω, since this rotation is coupled with the N-atom pyramidal inversion, requesting the introduction of a second dihedral angle "α." Full f(ω,α) potential energy surfaces of the different amide protonation states, critical points and isomerization reaction paths were determined, and the barriers of the neutral, O-protonated and N-deprotonated amides were found too high to allow cis-trans interconversion at room temperature: ∼85, ∼140, and ∼110 kJ mol-1, respectively. For the N-protonated amide bond, the cis form (ω = 0°) is a maximum rather than a minimum, and each ω state is accessible for less than ∼10 kJ mol-1. Here we outline a cis-trans isomerization pathway with a previously undescribed low energy transition state, which suggests that the proton is transferred from the more favorable O- to the N-protonation site with the aid of nearby water molecules, allowing the trans → cis transition to occur at an energy cost of ≤11.6 kJ mol-1. Our results help to explain why isomerase enzymes operate via protonated amide bonds and how N-protonation of the peptide bond occurs via O-protonation.


Identification of 2 Novel Polymorphisms and rs3138521 in 5' Untranslated Region of SERPINC1 Gene in North Indian Population With Deep Vein Thrombosis.
Antithrombin III (AT) is the most important endogenous anticoagulant, and genetic variability in SERPINC1, gene encoding AT, is low. Mutations leading to AT deficiency and increased thrombotic risk are well known; however, only 2 studies have reported mutations in regulatory region of SERPINC1 gene till date. Aim of the present study was to identify genetic variations in SERPINC1 5' untranslated region (UTR) in Indian patients with deep vein thrombosis (DVT) having AT deficiency. DNA sequencing was used to identify underlying genetic defects in SERPINC1 regulatory region. In silico tools TFBIND and PROMO were used to identify transcription factor binding sites in the promoter region. We have identified 2 novel polymorphisms, g.25G>A and g.-1A>T, and 2 known g.67G>A and rs3138521 5' UTR polymorphisms in SERPINC1 regulatory region in Indian patients with DVT for the first time. In present study, allele frequencies of rs3138521 (S: 0.37 and F: 0.63) were similar to that reported in Western population and were not associated with low plasma AT levels ( P value .5). This is the first report of regulatory region polymorphisms in SERPINC1 gene in Indian population. Our results strongly suggest that similar studies should be included when ever no mutation is detected in protein-coding region of AT gene.


Maintenance of autonomous genetic elements in twelve transgenic mouse strains established after transfer of pPyLT1 DNA.
Maintenance and efficient meiotic segregation of autonomous genetic elements in four transgenic mouse strains established after micro-injection of plasmid pPyLT1 were previously reported. These findings are now extended to a total of twelve independent transgenic families. In spite of extensive rearrangements, half of these plasmids maintained the region of pBR322 necessary for shuttle transfer in E. coli. They all included mouse DNA sequences and the same, or closely related sequences were present in distinct mouse strains.


Evaluating rare variants in complex disorders using next-generation sequencing.
Determining the genetic architecture of liability for complex neuropsychiatric disorders like autism spectrum disorders and schizophrenia poses a tremendous challenge for contemporary biomedical research. Here we discuss how genetic studies first tested, and rejected, the hypothesis that common variants with large effects account for the prevalence of these disorders. We then explore how the discovery of structural variation has contributed to our understanding of the etiology of these disorders. The rise of fast and inexpensive oligonucleotide sequencing and methods of targeted enrichment and their influence on the search for rare genetic variation contributing to complex neuropsychiatric disorders is the next focus of our article. Finally, we consider the technical challenges and future prospects for the use of next-generation sequencing to reveal the complex genetic architecture of complex neuropsychiatric disorders in both research and the clinical settings.


Distal Radius Fractures: AAOS Appropriate Use Criteria Versus Actual Management at a Level I Trauma Center.
The aim of this study is to determine whether the American Academy of Orthopaedic Surgeons' (AAOS) Appropriate Use Criteria (AUC) for distal radius fractures correlates with actual treatment by orthopedic hand surgeons at a level I trauma center. ICD-9 codes were used to retrospectively identify patients who presented with wrist fractures over 1 year. Patients with isolated distal radius fractures were evaluated using the AAOS AUC application for distal radius fractures. Actual treatment was then compared with treatment recommended by the AUC. Of the 112 patients, 64 (57%) received treatment that matched the AAOS AUC recommendation as an "appropriate treatment." Actual management matched the AUC recommendation 100%, 7%, and 50% of the time, for Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) type A, B, and C fractures, respectively. Surgery was performed for type A, B, and C fractures 30%, 7%, and 50% of the time, respectively. For type B fractures, only the 2 cases that were managed operatively were in agreement with the AUC. For type C fractures, increased patient age (57 years and older) was significantly associated with nonoperative treatment decisions. Surgeon decisions for nonoperative treatment were in agreement with the AUC recommendations 40% of the time, whereas surgeon decisions for surgery matched the AUC recommendations 97% of the time. We found low agreement between actual treatment decisions and the AUC-recommended "appropriate" treatments, especially for the type B and C fractures that were managed nonoperatively. The AUC favors surgery for all intra-articular fractures, while we emphasized age and fracture displacement in our decision-making process.


Function and regulation of class I ribonucleotide reductase-encoding genes in mycobacteria.
Ribonucleotide reductases (RNRs) are crucial to all living cells, since they provide deoxyribonucleotides (dNTPs) for DNA synthesis and repair. In Mycobacterium tuberculosis, a class Ib RNR comprising nrdE- and nrdF2-encoded subunits is essential for growth in vitro. Interestingly, the genome of this obligate human pathogen also contains the nrdF1 (Rv1981c) and nrdB (Rv0233) genes, encoding an alternate class Ib RNR small (R2) subunit and a putative class Ic RNR R2 subunit, respectively. However, the role(s) of these subunits in dNTP provision during M. tuberculosis pathogenesis is unknown. In this study, we demonstrate that nrdF1 and nrdB are dispensable for the growth and survival of M. tuberculosis after exposure to various stresses in vitro and, further, that neither gene is required for growth and survival in mice. These observations argue against a specialist role for the alternate R2 subunits under the conditions tested. Through the construction of nrdR-deficient mutants of M. tuberculosis and Mycobacterium smegmatis, we establish that the genes encoding the essential class Ib RNR subunits are specifically regulated by an NrdR-type repressor. Moreover, a strain of M. smegmatis mc(2)155 lacking the 56-kb chromosomal region, which includes duplicates of nrdHIE and nrdF2, and a mutant retaining only one copy of nrdF2 are shown to be hypersensitive to the class I RNR inhibitor hydroxyurea as a result of depleted levels of the target. Together, our observations identify a potential vulnerability in dNTP provision in mycobacteria and thereby offer a compelling rationale for pursuing the class Ib RNR as a target for drug discovery.


At the Borders of Bioethics.
What are the boundaries of bioethics? Where does bioethics give way to other kinds of ethics-organizational ethics, environmental ethics, social ethics, or just ethics? According to one commonly cited account of the origin of bioethics, the field always had a relatively broad remit; it was supposed to be about the ethics of the life sciences in general. In the early days of bioethics, however, the topic that seemed most in need of critical attention was the encounter between experts in medicine and the laity-doctors or medical researchers on the one hand and patients or medical research subjects on the other. Even given the narrow focal point, however, bioethics very naturally expanded. Much of the September-October 2018 issue of the Hastings Center Report either argues or assumes that bioethics extends well beyond into social ethics. A special report published as a supplement to this issue pushes the point explicitly.


Ascaridoid nematodes and associated lesions in stomachs of subadult male northern fur seals (Callorhinus ursinus) on St. Paul Island, Alaska: (1987-1999).
Stomachs from subadult male northern fur seals (SAMs) (Callorhinus ursinus) (n = 5,950) from St. Paul Island, Alaska, were examined from 1987 to 1999 for lesions and parasites. On gross examination of these stomachs, parasite nodules were evident in 92% of the stomachs and active and healing ulcers were found in 14% and 10%, respectively. Prevalence of nematodes from 1987 to 1997 was 88% for 5,700 SAMs for which numbers of parasites were estimated but not identified to the genus level. All nematodes recovered from 250 SAMs examined in 1998 (n = 124; 99% infected) and in 1999 (n = 126; 91% infected) were identified and counted. Prevalences in 1998 and 1999 were 5% and 0% for Anisakis spp., 52% and 18% for Contracaecum spp., and 96% and 89% for Pseudoterranova spp., respectively.


Central action of intraventricularly-injected midodrine in rats.
The aim of the present paper was to investigate the effect of intracerebroventricular (i.v.c.) injections of midodrine on the central nervous system of the rat. It was shown that midodrine increased locomotor activity, decreased body temperature, increased sedation in reserpinized rats and the cataleptic effect of haloperidol. Midodrine enhanced amphetamine-stimulated locomotor activity and reduced the amphetamine and apomorphine sterotypy. Phenoxybenzamine, yohimbine and clonidine inhibited the midodrine-induced hyperactivity. Midodrine depressed the whole brain noradrenaline (NA) and dopamine (DA) concentrations and reduced NA turnover. The results suggest a stimulating action of midodrine on the catecholaminergic neurons.


[Progress and challenge of Stanford type A aortic dissection in China].
In recent 20 years, the rapid development of acute Stanford type A aortic dissection in China has been mainly due to three aspects: (1) the refined classification of aortic dissection based on Stanford classification, (2) right axillary artery canal and selective cerebral perfusion technology become basic cardiopulmonary bypass strategy for Stanford type A aortic dissection, and (3) total aortic arch replacement and descending aortic stent graft surgery (Sun's surgery) become the standard treatment of Stanford type A aortic dissection. However, there are still many problems in the diagnosis and treatment of aortic dissection in China, such as: (1) unstandardized, lack of comprehensive guidelines of aortic dissection, (2) immature, perioperative organ protection and intraoperative blood protection technology remains a big flaw, and (3) it takes a long time to get patient prepared for surgery. In conclusion, as to the issue of the management of acute Stanford type A aortic dissection, there will be a long way for Chinese doctors to go. Peers should pay more attention to this problem and take more efforts, so that the outcome of acute Stanford type A aortic dissection surgical patients can be improved.


Fibromyalgia and Tinel's sign in the foot.
In the physical examination of the patient suspected of having tarsal tunnel syndrome, the podiatric physician relies on Tinel's sign: tapping the posterior tibial nerve in the tarsal tunnel should produce a distally radiating sensation if the nerve is pathologically compressed at this location. The American College of Rheumatology recognizes fibromyalgia as a condition characterized by multiple "tender points" on physical examination. This report compares the locations of the 18 critical diagnostic fibromyalgia points with known sites of anatomical entrapment of peripheral nerves in the lower extremity. We also describe a patient with both fibromyalgia and tarsal tunnel syndrome. Tinel's sign in the lower extremity is a valid technique for assessing peripheral nerve compression in the patient with fibromyalgia.


Method for the quantitative measurement of collecting lymphatic vessel contraction in mice.
Collecting lymphatic vessels are critical for the transport of lymph and its cellular contents to lymph nodes for both immune surveillance and the maintenance of tissue-fluid balance. Collecting lymphatic vessels drive lymph flow by autonomous contraction of smooth muscle cells that cover these vessels. Here we describe methods using intravital microscopy to image and quantify collecting lymphatic vessel contraction in mice. Our methods allow for the measurement of the strength of lymphatic contraction of an individual lymphangion in a mouse, which has not yet been demonstrated using other published methods. The ability to study murine collecting lymphatic vessel contraction-using the methods described here or other recently published techniques-allows the field to dissect the molecular mechanisms controlling lymphatic pumping under normal and pathological conditions using the wide variety of molecular tools and genetic models available in the mouse. We have used our methods to study lymphatic contraction in physiological and inflammatory conditions. The methods described here will facilitate the further study of lymphatic function in other pathological conditions that feature lymphatic complications.


Assessing the factor structure of a role functioning item bank.
Role functioning (RF) is an important part of health-related quality of life, but is hard to measure due to the wide definition of roles and fluctuations in role participation. This study aims to explore the dimensionality of a newly developed item bank assessing the impact of health on RF. A battery of measures with skip patterns including the new RF bank was completed by 2,500 participants answering only questions on social roles relevant to them. Confirmatory factor analyses were conducted for the participants answering items from all conceptual domains (N = 1193). Conceptually based dimensionality and method effects reflecting positively and negatively worded items were explored in a series of models. A bi-factor model (CFI = .93, RMSEA = .08) with one general and four conceptual factors (social, family, occupation, generic) was retained. Positively worded items were excluded from the final solution due to misfit. While a single factor model with methods factors had a poor fit (CFI = .88, RMSEA = .13), high loadings on the general factor in the bi-factor model suggest that the RF bank is sufficiently unidimensional for IRT analysis. The bank demonstrated sufficient unidimensionality for IRT-based calibration of all the items on a common metric and development of a computerized adaptive test.


The influence of cortisol excess on kidney function in the dog.
The effects of cortisol excess on kidney function were studied in 8 normal conscious dogs. Cortisol was given orally until polyuria developed. Cortisol excess decreased urine osmolality (from 897 +/- 76 to 186 +/- 36 mosm. kg-1) and increased urine production (from 0.7 +/- 0.1 to 9.3 +/- 2.4 ml kg-1. h-1). The glomerular filtration rate increased by 23 +/- 9 per cent. Sodium and potassium concentrations in plasma were decreased. 66 Per cent of the increase in urine production was due to the increase in free water clearance and 34 per cent to the increased urea excretion. Cortisol excess apparently caused polyuria by inhibition of the action of ADH in the collecting duct, resulting in a decreased water and urea reabsorption. The decreased urea reabsorption possibly causes a smaller urea recirculation in the renal medulla and hence a decrease in concentrating capacity.


A Facile Two-Step Hydrothermal Synthesis of Co(OH)2@NiCo2O4 Nanosheet Nanocomposites for Supercapacitor Electrodes.
The composites of NiCo2O4 with unique structures were substantially investigated as promising electrodes. In this study, the unique structured nanosheets anchored on nickel foam (Ni foam) were prepared under the hydrothermal technique of NiCo2O4 and subsequent preparation of Co(OH)2. The Co(OH)2@NiCo2O4 nanosheet composite has demonstrated higher specific capacitances owing to its excellent specific surface region, enhanced rate properties, and outstanding electrical conductivities. Moreover, the electrochemical properties were analyzed in a three-electrode configuration to study the sample material. The as-designed Co(OH)2@NiCo2O4 nanosheet achieves higher specific capacitances of 1308 F·g-1 at 0.5 A·g-1 and notable long cycles with 92.83% capacity retention over 6000 cycles. The Co(OH)2@NiCo2O4 nanosheet electrode exhibits a long life span and high capacitances compared with the NiCo2O4 and Co(OH)2 electrodes, respectively. These outstanding electrochemical properties are mainly because of their porous construction and the synergistic effects between NiCo2O4 and Co(OH)2. Such unique Co(OH)2@NiCo2O4 nanosheets not only display promising applications in renewable storage but also reiterate to scientists of the unlimited potential of high-performance materials.


Triiodothyronine (T3) and thyroxine (T4) levels in Rana curtipes during development and metamorphosis.
During premetamorphosis, levels of circulating triiodothyronine (T3) and thyroxine (T4) were below the limits of detection of RIA. They became detectable in late prometamorphic stages. A gradual increase in T3 and T4 was observed during this period. A sharp rise in hormone levels was apparent at the onset of metamorphic climax. Peak levels of both hormones were found at Taylor-Kollros stage XXI. The T3 reached a peak level of 101.4 ng/dl, about 3 fold increase over the level at prometamorphosis. Thereafter the circulating hormones (particularly T4) decreased rapidly and reached levels similar to prometamorphic stages. Significant high levels of thyroid hormones (T3 and T4) in metamorphic climax suggest that like other anurans, elevation of these hormones is required for normal metamorphosis in R. curtipes tadpoles.


Rapid Streptococcus Pneumonia Antigen Detection on Postmortem Urine in a Death Due to Pneumococcal Meningitis.
Streptococcus pneumoniae is the leading cause of adult bacterial meningitis. Differing from Neisseria meningitidis (the second most common cause of acute bacterial meningitis), contact tracing and chemoprophylaxis are not required. At postmortem, the differentiation between S. pneumoniae and N. meningitidis is traditionally done by culture and polymerase chain reaction performed on blood or cerebrospinal fluid, but may take hours, if not days, to analyze. We present a death from bacterial meningitis in a 73-year-old woman in which a rapid urinary pneumococcal antigen testing was able to identify S. pneumoniae as the causative organism within 1 hour. This was confirmed by subsequent brain swab culture. The rapid urinary pneumococcal antigen test in the case prevented the need for contact tracing and chemoprophylaxis. This case highlights the potential use of this test to rapidly identify the culprit organism at postmortem examination when acute bacterial meningitis is detected.


Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration.
The microvascular rheology and extent of pulmonary retention of second-generation microbubble ultrasound contrast agents has not previously been well characterized. We assessed the microvascular behavior of Definity, a lipid-shelled microbubble agent containing perfluoropropane gas, using intravital microscopy of either rat spinotrapezius muscle or mouse cremaster muscle. Immediately after intra-arterial injection, which was performed to model pulmonary retention, larger microbubbles (> 5 microm) were entrapped within small arterioles and capillaries. The retention fraction of microbubbles was low (1.2% +/- 0.1%) and entrapment was transient (85% dislodged by 10 minutes), resulting in no adverse hemodynamic effects. Leukocyte or platelet adhesion at the site of entrapment was not seen. After intravenous injection, no microbubble entrapment was observed and the velocities of microbubbles in arterioles, venules, and capillaries correlated well with those of red blood cells. We conclude that after intravenous injection and pulmonary passage, the microvascular rheology of Definity microbubbles is similar to that of red blood cells. Microbubble entrapment within the pulmonary microcirculation after venous injection should be negligible and transient. These findings are important for establishing the safety of this agent.


Predictors of Mortality in Pulmonary Sarcoidosis.
The goal of this study was to assess the prognostic strength of factors in predicting respiratory death in a large cohort of patients with sarcoidosis with at least 8 years' follow-up. Data were collected on age, sex, self-declared race, time of death, spirometry findings, diffusing capacity for carbon monoxide, chest radiograph stage, extent of fibrosis on high-resolution CT (HRCT) scanning, and presence of precapillary pulmonary hypertension (PH). The Gender-Age-Physiology (GAP) index and Walsh model criteria for high vs low risk were calculated. A total of 452 patients were identified who had complete pulmonary function testing and chest imaging. The median age at time of entry into the study was 50 years (range, 25-78 years). PH was confirmed by right heart catheterization in 29 (6.4%). Of 452 patients, 42 died during the time of the study, including 38 (8.4%) who died of sarcoidosis-associated respiratory failure and 4 who died of non-sarcoidosis causes. The overall mortality from sarcoidosis was 3.9% and 9.0% at 5 and 10 years, respectively. Alive patients were significantly younger than patients who died from sarcoidosis. Increased mortality was seen for black patients, stage 4 chest radiographs, > 20% fibrosis on HRCT scanning, or PH. The two composite scores (GAP and the Walsh model) were predictive of increased mortality according to univariate analysis. Using the Cox proportional hazards regression model, only age, extent of fibrosis on HRCT scanning, and PH were independent predictors of mortality. Although most patients with sarcoidosis do well, increased mortality was seen in those patients who were older, had extensive fibrosis on HRCT scanning, or who had PH.


An examination of the relationship between dynamic knee joint stiffness and gait pattern of children with cerebral palsy.
Dynamic joint stiffness represents the resistance that a joint opposes to an applied moment. Stiffness arises in conditions of joint laxity, instability and increased co-contraction and is commonly utilized as a means to stabilize the joint. The knee joint seems to be crucial for determining the walking pattern. The aim of this study was to investigate the association between the gait pattern, globally quantified by the Gait Profile Score (GPS), which indicates the 'quality' of a particular walking strategy, and knee dynamic joint stiffness (Kk) in children with diplegia. Kk is expressed by plotting the values of the knee flexion-extension moment versus the knee flexion-extension angle during weight acceptance. In this interval, the linear regression was fitted. The angular coefficient of the linear regression corresponded to the joint stiffness index. Sixty-one children with diplegia and 18 healthy individuals took part in this study. From their gait analysis data, the GPS (with its Gait Variable Scores-GVSs) and the Kk were calculated. Data showed that GPS (p = 2.73 × 10-21) and GVSs values for the patients with diplegia were higher in comparison to healthy controls. The Kk values for patients were not statistically different from those of controls. The correlation between Kk and GPS did not show the presence of any significant relationship (r = -0.04; p > 0.05). Thus, the functional limitation in diplegic children does not seems to be strictly related to Kk.


Tryptophan 2,3-dioxygenase may be a potential prognostic biomarker and immunotherapy target in cancer: A meta-analysis and bioinformatics analysis.
Tryptophan 2,3-dioxygenase (TDO2) is one of the emerging immune checkpoints. Meanwhile, TDO2 is also a key enzyme in the tryptophan (Trp)-kynurenine (Kyn) signaling pathway. Many studies have evaluated that TDO2 is highly expressed in various malignant tumor patients and plays a prognostic role. However, the sample size of a single prognostic study was small, and the results were still controversial. We used Stata software and referenced the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement to conduct a meta-analysis on TDO2 and its clinical features and prognosis. We searched the PubMed, Cochrane Library, and Web of Science databases to find publications concerning TDO2 expression in malignant tumor patients up to June 2021. We used the Newcastle-Ottawa Scale (NOS) to evaluate the bias risk of the included literature. Risk ratios (RRs) and hazard ratios (HRs) were used for clinical outcomes, specifically overall survival (OS) and progression-free survival (PFS). In addition, we used data from The Cancer Genome Atlas (TCGA) to verify our conclusions. Nine studies including 667 patients with malignant tumors were identified. Our results suggested that overexpression of TDO2 was statistically correlated with poor OS and poor PFS (HR = 2.58, 95% CI = 1.52-4.40, p = 0.0005; HR = 2.38, 95% CI = 0.99-5.73, p = 0.05). In terms of clinicopathological characteristics, the overexpression level of TDO2 was statistically correlated with TNM (tumor-node-metastasis) stage (RR = 0.65, 95% CI = 0.48-0.89, p = 0.002) and regional lymph node metastasis (RR = 0.76, 95% CI = 0.59-0.99, p = 0.04). Subgroup analysis revealed the potential sources of heterogeneity. In addition, bioinformatics studies suggested that the level of TDO2 was high in malignant tumors and higher in cancer tissue than in matched paracarcinoma tissue. Gene enrichment analysis showed that TDO2 was closely related to immune response. Overall, TDO2 may be a biomarker for the survival and prognosis of patients with malignant tumors and a potential therapeutic target in the future. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260442, identifier (CRD42021260442).


[Effects of 3,4,5-trimethoxy-N-(3-piperidyl) benzamide (KU-54) on respiration of the gastric mucosa and liver in rats].
Effects of 3,4,5-trimethoxy-N-(3-piperidyl) benzamide (KU-54), an antiulcer drug, on the tissue respiration of the gastric mucosa and the liver were studied in rats. Oral KU-54 at 100 mg/kg twice daily for 5 days (though it was given only once on the 5th day) caused an increase in oxygen consumption of the gastric mucosa in rats, but did not affect that of the liver. Thus the principal active site of KU-54 on tissue respiration was found to be the gastric mucosa. Oral KU-54 at 100 mg/kg once daily for 11 days significantly accelerated the oxygen consumption of marginal gastric mucosa of acetic acid ulcer in rats. The effect of oral gefarnate at 200 mg/kg was about half that of KU-54 at 100 mg/kg, but it was not significant. In addition, oral KU-54 at 100 mg/kg twice daily for 5 days (though it was given only once on the 5th day) significantly inhibited the decrease of oxygen consumption of the gastric mucosa in hemorrhagic shocked rats. The effect of oral gefarnate at 100 mg/kg was not like that at KU-54 at 100 mg/kg in conscious rats. When KU-54 was added in the incubation medium with small gastric mucosal fragments of rats, the increase of oxygen consumption of the gastric mucosa did not occur. Oral KU-54 at 100 mg/kg significantly accelerated a glycogen consumptive stimulation of the gastric mucosa of the corpus in ischemic rats, but the respiration of the antral mucosa was not accelerated under anaerobic incubating conditions. Oral gefarnate at 200 mg/kg accelerated an anaerobic glycolysis of the gastric antral mucosa in rats.


Moral reasoning and moral behavior among selected groups of practicing nurses.
This study examined the relationship between moral reasoning and moral behavior in 79 practicing nurses. Moral reasoning was measured by Rest's Defining Issues Test. Judgments about Nursing Decisions (JAND), developed by the investigator, was used to measure moral behavior. JAND is compromised of seven stories, each depicting a nurse in an ethical dilemma, with a total of 48 items. It measures two components of moral behavior: knowledge and valuation of ideal moral behavior and perception of realistic moral behavior. The hypothesis that moral reasoning would be positively related to knowledge and valuation of ideal moral behavior was tested by Pearson product moment correlation; the obtained coefficient of .28 was significant at the .01 level. The hypothesis that moral reasoning would be positively related to nurses' perception of realistic moral behavior was also tested by Pearson product moment correlation; the obtained coefficient of .19 was significant at the .05 level. Additional analyses showed significant differences in the knowledge and valuation component of JAND between educational groups, ethnic groups, age groups, and years of practice in nursing; but, there were no differences between these groups with respect to the perception of realist moral behavior component of JAND. Implications of the findings for nursing practice, education, and research are discussed.


The use of the Strengths and Difficulties Questionnaire (SDQ) in Southern European countries.
This paper reports a selection of completed or ongoing studies that have evaluated or applied the Strengths and Difficulties Questionnaire (SDQ) in five countries of Southern Europe: Italy, Spain, Portugal, Croatia, and France. In Italy, the SDQ has been used to study its concurrent validity with other norm-based instruments (Child Behavior Checklist-CBCL and Disruptive Behavior Disorder Rating Scale-DBDRS), to assess the efficacy of a behavioural school training, and as part of an epidemiological study. In Spain, the SDQ was used to analyse the association between respiratory and other behavioural problems. In Portugal and Croatia, psychometric properties of the three versions of the SDQ (parent, teacher, and self-reports) were investigated in samples of children ranging from 5 to 16 years. Past and ongoing studies in France have administered the SDQ to estimate inter-rater agreement between parents, teachers, and pupils, to carry out a large-scale epidemiological study, and to evaluate the efficacy of a parent training programme. In a second section, scale means obtained with the teacher version of the SDQ in three community-based samples of 7-8 year-old children from Italy, Portugal, and Spain are compared. The results show that, according to their teachers' ratings, Italian pupils showed less prosocial behaviour than their Spanish and Portuguese agemates, whereas the Portuguese children were rated as being more hyperactive and inattentive than comparable Italian and Spanish children. Possible causes underlying the observed differences between national SDQ means are discussed.


Yellow hyaline membrane disease. Identification of the pigment and bilirubin binding.
The distinguishing feature of yellow hyaline membrane disease (YHM) in the newborn is the presence of nonfading, bright yellow membrane lining the luminal aspects of conventional pink hyaline membranes (HM). Examination of yellow membranes, stained and unstained, under fluorescent microscopy reveals on orange-red fluorescent material heterogeneously dispersed within the membranes. Homogenates of lungs with YHM and HM were extracted with chloroform and tested spectrophotometrically, by thin layer chromatography, and for diazotized sulfanilic acid reactivity. Spectrophotometric profiles of YHM differed from those of HM by a unique absorption shoulder at 454 nm. in the former. This shoulder corresponded to the absorbance of unconjugated bilirubin. This profile could be reproduced by adding purified unconjugated bilirubin to non-YHM lung homogenate prior to extraction. Thin layer chromatography of the extracted YHM material produced two unique spots not found in extracts prepared from normal or HM-diseased lungs. These spots could be duplicated by thin layer chromatography using pure unconjugated bilirubin. The spots also fluoresced orange-red, the same color initially observed in the membranous preparations under fluorescent microscopy. Additional in vitro binding studies suggest that polymyxin, a decapeptide antibiotic used in endotracheal irrigation of newborn infants, binds bilirubin in pH-dependent, small molecular ratios. Although subsequent clinical studies disproved the etiologic significance of this particular drug, the unique properties of the bilirubin present in the YHMD lungs strongly suggest that the bilirubin there is bound by some yet unelucidated mechanism.


Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2.
There is evidence that serotonin [5-hydroxytryptamine (5-HT)] is involved in the physiological responses to hypercapnia. Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus. In the present study, we tested the hypothesis 1) that RMg plays a role in the ventilatory and thermal responses to hypercapnia, and 2) that RMg serotonergic neurons are involved in these responses. To this end, we microinjected 1) ibotenic acid to promote nonspecific lesioning of neurons in the RMg, or 2) anti-SERT-SAP (an immunotoxin that utilizes a monoclonal antibody to the third extracellular domain of the serotonin reuptake transporter) to specifically kill the serotonergic neurons in the RMg. Hypercapnia caused hyperventilation and hypothermia in all groups. RMg nonspecific lesions elicited a significant reduction of the ventilatory response to hypercapnia due to lower tidal volume (Vt) and respiratory frequency. Rats submitted to specific killing of RMg serotonergic neurons showed no consistent difference in ventilation during air breathing but had a decreased ventilatory response to CO(2) due to lower Vt. The hypercapnia-induced hypothermia was not affected by specific or nonspecific lesions of RMg serotonergic neurons. These data suggest that RMg serotonergic neurons do not participate in the tonic maintenance of ventilation during air breathing but contribute to the ventilatory response to CO(2). Ultimately, this nucleus may not be involved in the thermal responses to CO(2).


Optimal preservation of p21 ras immunoreactivity and morphology in paraffin-embedded tissue.
Specific immunostaining of p21 ras protein by the well-characterized pan-ras antibody Y13-259 is achieved in paraffin sections of human and animal tissues fixed in periodate-lysine-paraformaldehyde-dichromate (PLPD). Intensity of staining is as good as in cryostat sections, with superior histological detail. Localization to plasma membrane is demonstrated in rodent cells genetically manipulated to express abundant p21 ras (the FHO5T1 cell line), both in preparations suspended in agar after culture in vitro and in those growing as tumour in vivo. Strong positive staining is observed in neoplasms of human breast and colon, tissues in which there is independent evidence of elevated ras gene expression. The superior morphology afforded by this technique allows clear characterization of p21 ras expression in small premalignant lesions for which other methods of detection of oncogene expression are not appropriate.


Extended Förster theory for determining intraprotein distances. Part III. Partial donor-donor energy migration among reorienting fluorophores.
An extended Förster theory (EFT) is derived and outlined for electronic energy migration between two fluorescent molecules which are chemically identical, but photophysically non-identical. These molecules exhibit identical absorption and fluorescence spectra, while their fluorescence lifetimes differ. The latter means that the excitation probability becomes irreversible. Unlike the case of equal lifetimes, which is often referred to as, donor-donor energy migration (DDEM), the observed fluorescence relaxation is then no longer invariant to the energy migration process. To distinguish, the present case is therefore referred to as partial donor-donor energy migration (PDDEM). The EFT of PPDEM is described by a stochastic master equation (SME), which has been derived from the stochastic Liouville equation (SLE) of motion. The SME accounts for the reorienting as well as the translational motions of the interacting chromophores. Synthetic fluorescence lifetime and depolarisation data that mimics time-correlated single photon counting experiments have been generated and re-analysed. The rates of reorientation, as well as the orientational configurations of the interacting D-groups were examined. Moreover the EFT of PPDEM overcomes the classical "kappa(2)-problem" and the frequently applied approximation of kappa(2) = 2/3 in the data analyses. An outline for the analyses of fluorescence lifetime and depolarisation data is also given, which might prove applicable to structural studies of D-labelled macromolecules, e.g. proteins. The EFT presented here brings the analyses of PDDEM data to the same level of molecular detail as that used in ESR- and NMR-spectroscopy.


Chemical and thermal stability of Pt nanocubes synthesized with various surface-capping agents.
Pt nanocubes with a size of below 10 nm were synthesized by using various surface-capping agents of polyvinylpyrrolidone (PVP), tetradecyltrimethylammonium bromide (TTAB), and oleylamine with high shape purity. TGA and XPS data revealed the amount and characteristics of the residual organic molecules on the surface of Pt nanocubes. Chemical and thermal stability of these nanoparticles were examined by observing the change of cubic shape upon heating under different chemical environments of N2, H2 and air. The shape change such as rounding of the vertexes or aggregation depended on the type of surface-capping agent and chemical environments. The cubic shape generally started to deform at 200 degrees C and the nanoparticles were mostly fused together at 300 degrees C. The thermal treatment under air produced more PtO layer on the surface with less shape deformation or aggregation when compared with H2 or N2 treatments. Among three surface-capping agents used in this study, oleylamine-capped Pt nanocubes show the highest shape stability with no shape change or aggregation even at 300 degrees C under air.


A new species of Pasiphaea Savigny, 1816 (Crustacea, Decapoda, Pasiphaeidae) from the southwestern Atlantic.
The genus Pasiphaea Savigny, 1816 (Caridea: Pasiphaeidae) includes 71 species, of which vast majority inhabit in the meso or bathypelagic zones in the world oceans. A new species is described herein, sampled during the project "ABRACOS 2" (Acoustic along the BRazilian COast) nearby the Rocas Atoll and Fernando de Noronha Archipelago, in Brazilian waters. Pasiphaea antea n. sp. appears close to Pasiphaea dorsolineatus Komai Chan, 2012 described from off Hawaii, but is distinguished from the latter by the different shape of the rostrum, the mid-dorsal line of the carapace sharply carinate in the anterior half, and the possession of more numerous spiniform setae on the meri of the pereopods 1 and 2. This is the third species known from the southwestern Atlantic.


[Comparison of spiral CT, plain CT with surgical-pathological findings in peritoneal metastasis].
To compare enhanced spiral computed tomography (SCT), and plain CT with pathological findings in the diagnosis of peritoneal metastasis. Thirty-eight patients with peritoneal metastasis were examined by whole abdominal plain CT and enhanced SCT within one week before operation. The CT findings were compared with the pathological findings of specimens obtained during operation. In the early phase of contrast SCT, various degrees of enhancement were observed in the majority of peritoneal metastases. Primary cancers and the metastatic lesions were enhanced to same degree. For lesions with rich blood supply, a 2 mm metastatic lesion was usually detected by contrast SCT. The sensitivity of plain CT and enhanced SCT for the detection of peritoneal metastasis in all involvements were 46.7% and 76.6% (chi(2) = 29.07, P < 0.005). For contrast SCT, the detection rates of peritoneal carcinomatosis were higher then 83% in the fallopian tubes, ovary, subphrenic spaces, mesentery of small intestine, transverse colon and omentum. Enhanced spiral CT, being superior to plain CT, is effective in detecting and diagnosing peritoneal metastasis.


An unusual case of rectal carcinoid removed by transanal endoscopic microsurgery.
The name ''carcinoid'' was invented by Oberndorfer in 1907, when the nature of those histological entities was little understood. Usually, they were found in various locations in the gastrointestinal (GI) apparatus (67%), most of them in the small intestine (25%), appendix (12%), and rectum (14%).The techniques used for their removal are various. The authors present here a case of rectal carcinoid removed using the transanal endoscopic microsurgery technique, and referred to the diagnosis and treatment of this uncommon tumor. A 37-year-old male was admitted to the Santa Maria Hospital of Terni (Italy) with a chief complaint of intermittent pain in the lower right quadrant, that began three years ago. Complete blood count (CBC) and laboratory data as tumor markers and urinary 5-hydroxyindoleacetic acid (5-HIAA) showed no abnormalities, while urinary vanilmandelic acid level was elevate (18 mg/24 h). The patient was submitted to a colonoscopy with magnifying endoscopy and biopsy. The histological finding demonstrated a nodule characterized by cellular proliferation, with few microscopical abnormalities, arranged in small cords with a glandular pattern, separated by dense connective tissue. Histochemically the tumor cells were cytocheratins +/-, chromogranin positive, synaptophysine positive, CD56 positive and Growth Index MIB1-Ki67 which was almost zero. The patient also underwent an endoscopic ultrasonography and an Octreoscan. He was operated using a transanal endoscopic microsurgery technique. The use of Transanal Endoscopic Microsurgery (TEM) as a safe and feasible technique for exciding rectal tumors can be easily understood, for the excellent view and precise dissection. The use of new surgical devices as Harmonic Scalpel has improved the precision of this kind of approach, increasing the appropriateness of this approach compared to other kind of resection. A full diagnostic course and an immunohistochemistry are mandatory for precise diagnosis of rectal carcinoid. Careful attention must be paid to these tumors because of their unexpected behaviour.


Vacuolar protein sorting 35 (VPS35) acts as a tumor promoter via facilitating cell cycle progression in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is insidious and highly malignant with extremely poor prognosis and drug resistance to current chemotherapies. Therefore, there is a critical need to investigate the molecular mechanism underlying PDAC progression to develop promising diagnostic and therapeutic interventions. In parallel, vacuolar protein sorting (VPS) proteins, involved in the sorting, transportation, and localization of membrane proteins, have gradually attracted the attention of researchers in the development of cancers. Although VPS35 has been reported to promote carcinoma progression, the specific molecular mechanism is still unclear. Here, we determined the impact of VPS35 on the tumorigenesis of PDAC and explored the underlying molecular mechanism. We performed a pan-cancer analysis of 46 VPS genes using RNAseq data from GTEx (control) and TCGA (tumor) and predicted potential functions of VPS35 in PDAC by enrichment analysis. Furthermore, cell cloning experiments, gene knockout, cell cycle analysis, immunohistochemistry, and other molecular and biochemical experiments were used to validate the function of VPS35. Consequently, VPS35 was found overexpressed in multiple cancers and correlated with the poor prognosis of PDAC. Meanwhile, we verified that VPS35 could modulate the cell cycle and promote tumor cell growth in PDAC. Collectively, we provide solid evidence that VPS35 facilitates the cell cycle progression as a critical novel target in PDAC clinical therapy.


Sodium houttuyfonate attenuates neurological defects after traumatic brain injury in mice via inhibiting NLRP3 inflammasomes.
Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti-inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF-κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post-controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction (RT-PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF-κB. Moreover, SH significantly inhibited microglia activation post-CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF-κB signaling pathway. These findings explain the intracellular mechanism of the anti-inflammatory activity caused by SH treatment following TBI.


Needlestack: an ultra-sensitive variant caller for multi-sample next generation sequencing data.
The emergence of next-generation sequencing (NGS) has revolutionized the way of reaching a genome sequence, with the promise of potentially providing a comprehensive characterization of DNA variations. Nevertheless, detecting somatic mutations is still a difficult problem, in particular when trying to identify low abundance mutations, such as subclonal mutations, tumour-derived alterations in body fluids or somatic mutations from histological normal tissue. The main challenge is to precisely distinguish between sequencing artefacts and true mutations, particularly when the latter are so rare they reach similar abundance levels as artefacts. Here, we present needlestack, a highly sensitive variant caller, which directly learns from the data the level of systematic sequencing errors to accurately call mutations. Needlestack is based on the idea that the sequencing error rate can be dynamically estimated from analysing multiple samples together. We show that the sequencing error rate varies across alterations, illustrating the need to precisely estimate it. We evaluate the performance of needlestack for various types of variations, and we show that needlestack is robust among positions and outperforms existing state-of-the-art method for low abundance mutations. Needlestack, along with its source code is freely available on the GitHub platform: https://github.com/IARCbioinfo/needlestack.


Using Airborne Hyperspectral Imaging Spectroscopy to Accurately Monitor Invasive and Expansive Herb Plants: Limitations and Requirements of the Method.
Remote sensing (RS) is currently regarded as one of the standard tools used for mapping invasive and expansive plants for scientific purposes and it is increasingly widely used in nature conservation management. The applicability of RS methods is determined by its limitations and requirements. One of the most important limitations is the species percentage cover at which the classification result is correct and useful for nature conservation. The primary objective, carried out in 2017 in three areas of Poland, was to determine the minimum percentage cover from which it is possible to identify a target species by RS methods. A secondary objective of this research, related to the requirements of the method, was to optimize the set of training polygons for a target species in terms of the number of polygons and abundance percentage cover of the target species. Our method has to be easy to use, effective, and applicable, therefore the analysis was carried out using the basic set of rasters-the first 30 channels after the Minimum Noise Fraction (MNF) transformation (the mosaic of hyperspectral data from HySpex sensors with spectral range 0.4-2.5 µm) and commonly used Random Forest algorithm. The analysis used airborne hyperspectral data with a spatial resolution of 1 m to perform classification of one invasive and three expansive plants-two grasses and two large perennials. On-ground training and validation data sets were collected simultaneously with airborne data collection. When testing different classification scenarios, only the set of training polygons for a target species was changed. Classification results were evaluated based on three methods: accuracy measures (Kappa and F1), true-positive pixels in subclasses with different species cover and compatibility with field mapping. The classification results indicate that to classify the target plant species at the accepted level, the training dataset should contain polygons with a species cover ranging from 80-100%. Training performed only using polygons with a species characterized by a variable, but lower, cover (20-70%) and missing samples in the 80-100% range, led to a map which was not acceptable because of a high overestimation of target species. We achieved effective identification of species in areas where the species cover is above 50%, considering that ecosystems are heterogeneous. The results of these studies developed a methodology of field data acquisition and the necessity of synchronization in the acquisition of airborne data, and training and validation of on-ground sampling.


Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner.
As described elsewhere in this Special Issue on biomarkers, much progress has been made in the detection of modified DNA within organisms at endogenous and exogenous levels of exposure to chemical species, including putative carcinogens and chemotherapeutic agents. Advances in the detection of damaged or unnatural bases have been able to provide correlations to support or refute hypotheses between the level of exposure to oxidative, alkylative, and other stresses, and the resulting DNA damage (lesion formation). However, such stresses can form a plethora of modified nucleobases, and it is therefore difficult to determine the individual contribution of a particular modification to alter a cell's genetic fate, as measured in the form of toxicity by stalled replication past the damage, by subsequent mutation, and by lesion repair. Chemical incorporation of a modification at a specific site within a vector (site-specific mutagenesis) has been a useful tool to deconvolute what types of damage quantified in biologically relevant systems may lead to toxicity and/or mutagenicity, thereby allowing researchers to focus on the most relevant biomarkers that may impact human health. Here, we will review a sampling of the DNA modifications that have been studied by shuttle vector techniques.


[Correlation analysis of quality,origin and phenotypic characters of Paris polyphylla var. yunnanensis].
In order to provide guidance for the protection and utilization of resources,quality control and breeding of improved varieties,we compared the main phenotypic characters and quality of wild and transplanted Paris polyphylla var. yunnanensis collected from different producing areas. Seven phenotypic characters of 33 samples of P. polyphylla var. yunnanensis collected from Yunnan,Guizhou and Sichuan were determined by conventional methods,and the principal component analysis and cluster analysis were used to analyze the diversity of the samples. The parissaponin( polyphyllin Ⅰ,Ⅱ,Ⅵ,Ⅶ) content of the samples were detected by HPLC,and analyzed by cluster analysis. Correlation analysis of the phenotypic characters and the parissaponin content was performed. There were significant differences in seven phenotypic characters between wild and transplanted samples of P. polyphylla var. yunnanensis from different habitats,with high phenotypic diversity and abundant genetic variation. The results of principal component analysis showed that leaf shape index was the main factor of morphological variation of P. polyphylla var. yunnanensis. Cluster analysis showed that the phenotypic characters of wild and transplanted P. polyphylla var. yunnanensis could not be completely separated. The content of saponins in wild and transplanted samples from different habitats was quite different. Saponins content of 93. 94% samples met the criterion of Chinese Pharmacopoeia 2015 edition,and the overall quality was relatively steady. The results of independent sample t-test showed that there was no significant difference of all the active ingredient between wild and transplanted samples,and it couldn't be used to distinguish between wild and transplanted samples. It is the same as the results of cluster analysis. The results of correlation analysis showed that the phenotypic traits of P. polyphylla var. yunnanensis were correlated with its medicine quality,and the total content of saponins was positively correlated with leaf length and leaf shape index( r = 0. 389,0. 441; P<0. 05). Yunnan,Guizhou and Sichuan are suitable for the growth of P. polyphylla var. yunnanensis. And the transplaned P. polyphylla var. yunnanensis can be used as the same as the wild ones completely. The results provide reference for the protection and selective breeding of P. polyphylla var. yunnanensis.


Application of magnetic techniques in the field of drug discovery and biomedicine.
Magnetic separation technology, using magnetic particles, is quick and easy method for sensitive and reliable capture of specific proteins, genetic material and other biomolecules. The technique offers an advantage in terms of subjecting the analyte to very little mechanical stress compared to other methods. Secondly, these methods are non-laborious, cheap and often highly scalable. Moreover, techniques employing magnetism are more amenable to automation and miniaturization. Now that the human genome is sequenced and about 30,000 genes are annotated, the next step is to identify the function of these individual genes, carrying out genotyping studies for allelic variation and SNP analysis, ultimately leading to identification of novel drug targets. In this post-genomic era, technologies based on magnetic separation are becoming an integral part of todays biology laboratory. This article briefly reviews the selected applications of magnetic separation techniques in the field of biotechnology, biomedicine and drug discovery.


[Immunosuppressive therapy in congestive cardiomyopathy in childhood].
Two patients aged ten and fourteen years presented with clinical signs of acute viral myocarditis and cardiac failure. Within three months both showed clinical deterioration with development of severe mitral and tricuspid incompetence. From their third month of illness myocardial antibodies were constantly found by indirect immunofluorescence technique. Both were treated with prednisone 2 mg/kg/d and azothioprine 2-2,5 mg/kg/d from their ninth and third month of illness for fifteen and twelve months respectively. Both showed considerable improvement within weeks with resolution of their valve incompetence, diminution of heart size and normalization of their ECGs. Results from myocardial biopsies suggest that a number of patients with chronic congestive cardiomyopathy may have long lasting viral inflammation of the myocardium or myocardial fiber destruction by autoimmunmechanisms after viral infection. Our cases probably had acute myocarditis which led to chronic congestive cardiomyopathy. Immunosuppressive therapy seems to be justified in cases where chronic inflammation or destruction of the myocardium is suspected because of the results of cardiac biopsies, myocardial scintigraphy or demonstration of myocardial antibodies.


Human distal lung maps and lineage hierarchies reveal a bipotent progenitor.
Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases1-4. Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not-to our knowledge-been previously characterized. These include airway-associated LGR5+ fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5+ fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung5-7. Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease.


Statistics of level spacing of geometric resonances in random binary composites.
We study the statistics of level spacing of geometric resonances in the disordered binary networks. For a definite concentration p within the interval [0.2,0.7], numerical calculations indicate that the unfolded level spacing distribution P(t) and level number variance Sigma(2)(L) have general features. It is also shown that the short-range fluctuation P(t) and long-range spectral correlation Sigma(2)(L) lie between the profiles of the Poisson ensemble and Gaussion orthogonal ensemble. At the percolation threshold p(c), crossover behavior of functions P(t) and Sigma(2)(L) is obtained, giving the finite size scaling of mean level spacing delta and mean level number n, which obey the scaling laws, delta=1.032L(-1.952) and n=0.911L(1.970).


Neuroanatomical substrates of late-life minor depression. A quantitative magnetic resonance imaging study.
To examine the neuroanatomical correlates of late-life minor depression using magnetic resonance imaging. Cross-sectional quantitative magnetic resonance imaging study of elderly patients with minor depression and age-matched controls. Patients and controls were recruited from the community through advertisements to the Section of Geriatric Psychiatry, University of Pennsylvania, Philadelphia. Our sample included 18 subjects diagnosed as having minor depression using the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, research criteria and 31 controls without depression. Patients were free of other central nervous system disease and both groups had comparable degrees of medical comorbidity. All images were acquired on a 1.5-T scanner and absolute and normalized quantitative measures of global and focal brain and cerebrospinal fluid volumes were compared between groups. Prefrontal lobe volume was significantly smaller in the group with minor depression (P = .002) compared with controls after controlling for age, sex, and age by sex interactions. More global measures of brain and cerebrospinal fluid volumes were comparable in both groups. These data suggest that focal prefrontal atrophy may provide an important neuroanatomical substrate in late-life minor depression.


Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice.
One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3-4 months) and old (20-22 months) male and female mice of wt and arginase-II knockout (arg-ii-/-) were used. Albuminuria was employed as a readout of glomerular function. Cellular localization and expression of Arg-II in glomeruli were analyzed using an immunofluorescence confocal microscope. A more pronounced age-associated increase in albuminuria was found in male than in female mice. An age-associated induction of Arg-II in glomeruli and podocytes (as demonstrated by co-localization of Arg-II with the podocyte marker synaptopodin) was also observed in males but not in females. Ablation of the arg-ii gene in mice significantly reduces age-associated albuminuria in males. Also, age-associated decreases in podocyte density and glomerulus hypertrophy are significantly prevented in male arg-ii-/- but not in female mice. However, age-associated glomerulosclerosis is not affected by arg-ii ablation in both sexes. These results demonstrate a role of Arg-II in sex-specific podocyte injury in aging. They may explain the sex-specific differences in the development of renal disease in humans during aging.


Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3.
Biliary atresia (BA) is a progressive, idiopathic obliteration of the extrahepatic biliary system occurring exclusively in the neonatal period. It is the most common disease leading to liver transplantation in children. The etiology of BA is unknown, although infectious, immune and genetic causes have been suggested. Although the recurrence of BA in families is not common, there are more than 30 multiplex families reported and an underlying genetic susceptibility has been hypothesized. We screened a cohort of 35 BA patients for genomic alterations that might confer susceptibility to BA. DNA was genotyped on the Illumina Human Hap 550 Beadchip platform, which analyzes over 550,000 single nucleotide polymorphisms (SNPs) for genomic deletions and duplications. Areas of increased and decreased copy number were compared to those found in control populations. To identify regions that could serve as susceptibility factors for BA, we searched for regions that were found in BA patients, but not in controls. We identified two unrelated BA patients with overlapping heterozygous deletions of 2q37.3. Patient 1 had a 1.76 Mb (280 SNP), heterozygous deletion containing 30 genes. Patient 2 had a 5.87 Mb (1,346 SNP) heterozygous deletion containing 55 genes. The overlapping 1.76 Mb deletion on chromosome 2q37.3 from 240,936,900 to 242,692,820 constitutes the critical region and the genes within this region could be candidates for susceptibility to BA.


Use of sodium restriction and enalapril in persons with moderate to severe hypertension.
One hundred and seventy-four patients who were receiving drug therapy for hypertension were asked to restrict their sodium intake for three months. At the end of that time their drug therapy was replaced with enalapril and the dose of the drug "titrated" to obtain a diastolic blood pressure of less than 90 mmHg. Sodium restriction caused a small fall in blood pressure and could be used as sole therapy in only 6% of patients. Enalapril therapy was instituted without problems and control of blood pressure below 90 mmHg was achieved in 62% of persons with monotherapy. The number of tablets of enalapril that were taken was reduced from 5.9 to 2.7; in most patients these were taken once a day. There were few side-effects and no depression of white cell count, no proteinuria and no deterioration of renal function. Seventy-six per cent of patients preferred the new regimen either because they felt better than with their previous therapy (52%) or because of the more simple regimen (24%). Enalapril was an effective, well tolerated antihypertensive agent and potentially has a major role to play in the management of patients with high blood pressure.


Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA).
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population. It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA). Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity. In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).


The Leeds scales for the self-assessment of anxiety and depression.
Self-rating scales are finding an increasing use in psychiatric work. Not only are they widely used in research, but they provide the clinician with a score indicating the patient's psychiatric state at any one time, and these scores if repeated throughout the duration of treatment may be considered to provide a continuing measure of the severity of the illness, as does a temperature chart in a febrile illness. Most scales could be improved by item analysis, and in this study the Wakefield Self-Assessment of Depression Inventory, with added items, was subjected to statistical analysis. It was found that valid scales could be constructed for the measurement of anxiety and of depression in general psychiatric disorders, as well as scales for the measurement of the severity of endogenous (primary) depression and of anxiety states. In addition, the derivation of a 'diagnostic' score was confirmed in a cross-validation study and may be found of use both in research and in clinical practice.


Rapid visual detection of highly pathogenic Streptococcus suis serotype 2 isolates by use of loop-mediated isothermal amplification.
Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that causes considerable economic losses to the pig industry and significantly threatens public health worldwide. The highly pathogenic S. suis 2, which contains the 89K pathogenicity island (PAI), has caused large-scale outbreaks of infections in humans, resulting in high mortality rates. In this study, we established two loop-mediated isothermal amplification (LAMP)-based assays that can rapidly detect S. suis 2 and the 89K PAI and can be performed simultaneously under the same conditions. Further, based on the findings of these two LAMP assays and using the same set of serially diluted DNA samples, we compared the sensitivities of different LAMP product detection methods, including SYBR green detection, gel electrophoresis, turbidimetry, calcein assays, and hydroxynaphthol blue detection. The results suggest that target genes can be amplified and detected within 48 min under 63°C isothermal conditions. The sensitivity of tests for S. suis 2 detection varies between detection methods and reaction systems, indicating that for each LAMP reaction system, multiple detection methods should be performed to select the optimal one. The sensitivities of the optimized methods (7.16 copies/reaction) in the present study were identical to those of the real-time PCR assay, and the test results for reference strains and clinical samples showed that these LAMP systems have high specificities. Thus, since the LAMP systems established in this study are simple, fast, and sensitive, they may have good clinical potential for detecting the highly pathogenic S. suis 2.


Successful HIV treatment: lessons learned.
To review current insights concerning treatment of human immunodeficiency virus (HIV). The range of antiretroviral agents available for treating patients who have HIV/AIDS (acquired immunodeficiency syndrome) has expanded to 20 medications since the first, zidovudine, was approved in 1987. While the exact choice of drugs to use in treatment must be tailored to the patient, depending on safety and tolerance, the ultimate goal is durable suppression of the HIV virus. Highly active antiretroviral treatment (HAART) is the current standard of care and involves treating the patient with a combination of antiretrovirals. First-line regimens usually contain a combination of 2 nucleoside reverse transcriptase inhibitors plus either one nonnucleoside or protease inhibitor. Differences in side effects have become more important than differences in efficacy in determining the choice of the initial antiretroviral regimen. To prevent the development of viral resistance to treatment, it is essential to begin treatment with all medications simultaneously, rather than sequentially. If the initial HAART regimen fails, more complex regimens that involve adding at least 2 new antiretrovirals can often reestablish control, even in patients with extensive pretreatment and in whom there was the development of viral resistance. For patients with HIV/AIDS embarking on treatment today, the durability of HIV suppression in optimal regimens suggests that a normal lifespan is now a realistic outcome of HIV treatment.


Alginate microparticles as novel carrier for oral insulin delivery.
Alginate microparticles produced by emulsification/internal gelation were investigated as a promising carrier for insulin delivery. The procedure involves the dispersion of alginate solution containing insulin protein, into a water immiscible phase. Gelation is triggered in situ by instantaneous release of ionic calcium from carbonate complex via gentle pH adjustment. Particle size is controlled through the emulsification parameters, yielding insulin-loaded microparticles. Particle recovery was compared using several washing protocols. Recovery strategies are proposed and the influence on particle mean size, morphology, recovery yield (RY), encapsulation efficiency, insulin release profile, and structural integrity of released insulin were evaluated. Spherical micron-sized particles loaded with insulin were produced. The recovery process was optimized, improving yield, and ensuring removal of residual oil from the particle surface. The optimum recovery strategy consisted in successive washing with a mixture of acetone/hexane/isopropanol coupled with centrifugation. This strategy led to small spherical particles with an encapsulation efficiency of 80% and a RY around 70%. In vitro release studies showed that alginate itself was not able to suppress insulin release in acidic media; however, this strategy preserves the secondary structure of insulin. Particles had a mean size lower than the critical diameter necessary to be orally absorbed through the intestinal mucosa followed by their passage to systemic circulation and thus can be considered as a promising technology for insulin delivery.


Mac 387 antibody and detection of formalin resistant myelomonocytic L1 antigen.
The murine monoclonal antibody Mac 387 was raised against a purified protein fraction obtained from human monocytes. By immunoblotting experiments, Mac 387 was shown to react with a previously defined antigen called L1; this is a multichain myelomoncytic protein of about 36 Kd which shows sequence homology with the cystic fibrosis antigen. The L1 protein is present in the cytoplasm of virtually all resting peripheral neutrophils and monocytes; it is also variably expressed on the plasma membrane of these cells, possibly as a secretory product. Because the L1 antigen is resistant to denaturation by formalin, its tissue distribution can be studied in routinely processed biopsy material. In a wide variety of specimens Mac 387 was shown by immunohistochemical analysis, to produce a cytoplasmic staining pattern concordant with that of a well defined polyclonal antibody to the L1 antigen. Cytoplasmic reactivity was obtained with granulocytes and infiltrating macrophages but generally not with several categories of dendritic cells. In addition, squamous epithelium of mucous membranes was strongly positive, in contrast to normal epidermis.


Transcranial Direct Current Stimulation in Substance Use Disorders: A Systematic Review of Scientific Literature.
New treatment options such as noninvasive brain stimulation have been recently explored in the field of substance use disorders (SUDs), including transcranial direct current stimulation (tDCS). In light of this, we have performed a review of the scientific literature to assess efficacy and technical and methodological issues resulting from applying tDCS to the field of SUDs. Our analysis highlighted the following selection criteria: clinical studies on tDCS and SUDs (alcohol, caffeine, cannabis, cocaine, heroin, methamphetamine, and nicotine). Study selection, data analysis, and reporting were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Exclusion criteria were as follows: clinical studies about tDCS among behavioral addiction; review and didactic articles; physiopathological studies; and case reports. Eighteen scientific papers were selected out of 48 articles. Among these, 16 studied the efficacy of tDCS applied to the dorsolateral prefrontal cortex, and 8 suggested the efficacy of tDCS in reducing substance craving. In light of these data, it is premature to conclude that tDCS over the dorsolateral prefrontal cortex is a very efficient technique in reducing craving. Small sample size, different stimulation protocols, and study duration were the main limitations. However, the efficacy of tDCS in treating SUDs requires further investigation.


Plasminogen carbohydrate side chains in receptor binding and enzyme activation: a study of C6 glioma cells and primary cultures of rat hepatocytes.
The human [Glu1]-plasminogen carbohydrate isozymes, plasminogen type I (Pg 1) and plasminogen type II (Pg 2), were separated by chromatography and studied in cell binding experiments at 4 degrees C with primary cultures of rat hepatocytes and rat C6 glioma cells. In both cell systems, Pg 1 and Pg 2 bound to an equivalent number of receptors, apparently representing the same population of surface molecules. The affinity for Pg 2 was slightly higher. With hepatocytes, the KD for Pg 1 was 3.2 +/- 0.2 microM, and the KD for Pg 2 was 1.9 +/- 0.1 microM, as determined from Scatchard transformations of the binding isotherms. The Bmax was approximately the same for both isozymes. With C6 cells, the KD for Pg 1 was 2.2 +/- 0.1 microM vs. 1.5 +/- 0.2 microM for Pg 2. Again, the Bmax was similar with both isozymes. 125I-Pg 1 and 125I-Pg 2 were displaced from specific binding sites by either nonradiolabeled isozyme. The KI for Pg 2 was slightly lower than the KI for Pg 1 with hepatocytes (0.9 vs. 1.3 microM) and with C6 cells (0.6 vs. 1.1 microM). No displacement was detected with miniplasminogen at concentrations up to 5.0 microM. Activation of Pg 1 and Pg 2 by recombinant two-chain tissue-plasminogen activator (rt-PA) was enhanced by hepatocyte cultures. The enhancing effect was greater with Pg 2. Hepatocyte cultures did not affect the activation of miniplasminogen by rt-PA or the activation of plasminogen by streptokinase. Unlike the hepatocytes, C6 cells did not enhance the activation of plasminogen by rt-PA or streptokinase; however, plasmin generated in the presence of C6 cells reacted less readily with alpha 2-antiplasmin.


Chemical composition and in vitro evaluation of the cytotoxic and antioxidant activities of supercritical carbon dioxide extracts of pitaya (dragon fruit) peel.
Hylocereus polyrhizus and Hylocereus undatus are two varieties of the commonly called pitaya fruits, and pitaya fruits have gained popularity in many countries all over the world. However, studies on chemical composition and the nutritional quality of pitaya flesh peel are limited. Extracts of pitaya (H. polyrhizus and H. undatus) peel were extracted by supercritical carbon dioxide extraction, and analyzed by gas chromatography-mass spectrometry analysis. Their cytotoxic and antioxidant activities were investigated. The main components of H. polyrhizus extract were β-amyrin (15.87%), α-amyrin (13.90%), octacosane (12.2%), γ-sitosterol (9.35%), octadecane (6.27%), 1-tetracosanol (5.19%), stigmast-4-en-3-one (4.65%), and campesterol (4.16%), whereas H. undatus were β-amyrin (23.39%), γ-sitosterol (19.32%), and octadecane (9.25%), heptacosane (5.52%), campesterol (5.27%), nonacosane (5.02%), and trichloroacetic acid, hexadecyl ester (5.21%). Both of the two extracts possessed good cytotoxic activities against PC3, Bcap-37, and MGC-803 cells (IC50 values ranging from 0.61 to 0.73 mg/mL), and the activities of their main components were also studied. Furthermore, these extracts also presented some radical scavenging activities, with IC50 values of 0.83 and 0.91 mg/mL, respectively. This paper provides evidence for studying the chemical composition of supercritical carbon dioxide extracts of pitaya peel and their biological activity.


[Recurrence of glomerulonephritis in transplanted kidney].
Recent advances in immunosuppressive therapy have dramatically reduced the incidence of acute rejection, thus improving graft survival. As a result, the importance of recurrence of the original nephropathy as a factor affecting the long-term outcome of the graft has grown considerably The incidence of recurrence increases with the increase in graft survival and can currently be estimated between 6 and 15% 10 years after surgery, with great variability among the different histological types of nephropathy. More than 50% of patients with recurrence experience progressive deterioration of graft function, and recurrence of the nephropathy accounts for long-term graft failure in more than 15% of cases. The original disease should be duly considered in all candidates for renal transplantation to identify patients at higher risk for recurrence and to define those treatment protocols devoted to risk reduction. Finally, the risk of disease recurrence should always be included among the parameters used in evaluating a possible transplantation from living donor.


The bizarreness effect and individual differences in imaging ability.
The bizarreness effect refers to the superior performance in recall of bizarre sentences as compared to common sentences. The subjects studied each target word and in Exp. 1 rated its congruity with its sentence frame. In Exp. 2 they rated the vividness of the image for each sentence frame in which it was included. Four types of sentence frames were provided: bizarre image sentences, bizarre nonimage sentences, common image sentences, and common nonimage sentences. Good imagers and poor imagers were assessed on the Questionnaire Upon Mental Imagery. Both experiments showed that good imagers recalled target words in bizarre image sentences better than target words in common image sentences. A difference between the two sentence types was not observed for poor imagers. The differences between bizarre nonimage sentences and common nonimage sentences were not found for both type of imagers. The results were interpreted as showing that a difference in imaging ability was critical for the occurrence of a bizarreness effect.