FoxM1 influences embryo implantation and is regulated by 17 beta-estradiol and progesterone in mouse uteri and endometrium cells.
To be a successful implantation, endometrial receptivity should be established. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion, and progression. FoxM1 regulates the expression of lots of targeted genes important to cell differentiation, proliferation and apoptosis; cell-cycle progression; and tumor angiogenesis, migration, invasion, and metastasis. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. To test our hypothesis, we observed the expression and distribution of FoxM1 during the early pregnancy of mouse. Then, we used Immunohistochemistry to examine the expression of FoxM1 induced by E2 and/or P4 in the ovariectomized mouse uterus and human endometrium cells. This study further investigated whether FoxM1 was an important factor in the implantation. Our results showed that FoxM1 expressed in the mouse uterus during early pregnancy (Day 1 to 5). The expression of FoxM1 gradually increased along pregnancy process; FoxM1 expression could be increased by E2. On the contrary, FoxM1 expression could be decreased by P4 and E2 plus P4. We also detected the proliferation of human endometrium cells. We found that E2 might promote cells proliferation, while P4 and E2 plus P4 inhibited cells proliferation; Inhibiting FoxM1 could interfere the embryo implantation of mouse. Amplification or inhibiting of FoxM1 in JAR cells can increase or decrease the adhesion rate to Rl95-2 and HEC-1A cells separately. Our data indicate that FoxM1 might play an important role during the process of mouse embryo implantation.


Isolation of Northway serotype and other Bunyamwera serogroup bunyaviruses from California and Oregon mosquitoes, 1969-1985.
Eight previously untyped Bunyamwera serogroup bunyaviruses that had been isolated from mosquitoes collected in California and Oregon between 1969 and 1985, were identified by cross-neutralization tests. Four viruses from Anopheles freeborni and a virus from Aedes sierrensis collected in Butte County in the Central Valley of California in 1970-71 were shown to belong to the Northway serotype. The existence of a Northway serotype virus in California had been inferred from previous serologic surveys of deer and horses, but these are the first Northway serotype viruses to be identified from the contiguous United States or from An. freeborni. This is also the first isolation of any virus from Ae. sierrensis. Two viruses from Culiseta inornata collected in Umatilla County, Oregon in 1969 may represent a new serotype in the Bunyamwera serocomplex of the Bunyamwera serogroup. The name "Stanfield" is proposed for this serotype, which is closely related to the Cache Valley and Northway bunyavirus serotypes. A virus from Ae. taeniorhynchus collected in San Diego County, California in 1985 was confirmed to belong to the Main Drain serotype. Previously, Main Drain serotype viruses in California have been associated principally with Culicoides variipennis.


Perception of the risk of gastrointestinal adverse drug reactions with non-steroidal anti-inflammatory drugs (including coxibs): differences among general practitioners, gastroenterologists and rheumatologists.
To compare the perception of risk of gastrointestinal adverse drug reactions (ADRs) with non-steroidal anti-inflammatory drugs (NSAIDs) (including coxibs) in general practitioners, gastroenterologists and rheumatologists. Physicians (69 general practitioners, 45 gastroenterologists and 58 rheumatologists; 172 total) were interviewed using visual analogue scales in order to define a score of perceived risk (ranking from 0 to 10) of gastrointestinal ADRs associated with four classes of NSAIDs (indolics, oxicams, arylcarboxylic derivatives, coxibs). When the three groups of physicians were taken as a whole, indolic derivatives were ranked as the most dangerous NSAIDs [median score: 5.3 (25-75th percentiles: 3.5-7)] followed by oxicams [median score: 5.0 (25-75th percentiles: 3.1-6.2)], arylcarboxylic derivatives [median score 4.7 (25-75th percentiles: 3.0-6.5)] and coxibs [median score 1.9 (25-75th percentiles: 1.2-3.0)]. Among physicians, general practitioners gave the most important mean score [median score 4.8 (25-75th percentiles: 3.4-5.7)] for NSAIDs as a whole followed by gastroenterologists [median score 4.6 (25-75th percentiles: 3.6-5.6)] and rheumatologists [median score 3.6 (25-75th percentiles: 2.3-4.7)]. There was no significant difference among the three groups of physicians in the median score of perceived digestive risk associated with the use of indolic derivatives, whereas significant differences were found for arylcarboxylic derivatives, oxicams and coxibs, with higher median scores given by gastroenterologists followed by general practitioners and rheumatologists. This study shows differences in the perception of risks of gastrointestinal ADRs. Rheumatologists systematically considered NSAIDs as less harmful than general practitioners and gastroenterologists did. In contrast, the widely demonstrated difference in gastrointestinal risk among the different groups of NSAIDS (with, for example, a higher risk for oxicams) was not pointed out by the three studied groups of physicians. There are differences in the perception of gastrointestinal risks of NSAIDs (including coxibs) among physicians according to their medical education and medical specialisation.


CT versus MR Techniques in the Detection of Cervical Artery Dissection.
Spontaneous cervical artery dissection (sCAD) is an important etiology of juvenile stroke. The gold standard for the diagnosis of sCAD is convential angiography. However, magnetic resonance imaging (MRI)/MR angiography (MRA) and computed tomography (CT)/CT angiography (CTA) are frequently used alternatives. New developments such as multislice CT/CTA have enabled routine acquisition of thinner sections with rapid imaging times. The goal of this study was to compare the capability of recent developed 128-slice CT/CTA to MRI/MRA to detect radiologic features of sCAD. Retrospective review of patients with suspected sCAD (n = 188) in a database of our Stroke center (2008-2014), who underwent CT/CTA and MRI/MRA on initial clinical work-up. A control group of 26 patients was added. All Images were evaluated concerning specific and sensitive radiological features for dissection by two experienced neuroradiologists. Imaging features were compared between the two modalities. Forty patients with 43 dissected arteries received both modalities (29 internal carotid arteries [ICAs] and 14 vertebral arteries [VAs]). All CADs were identified in CT/CTA and MRI/MRA. The features intimal flap, stenosis, and lumen irregularity appeared in both modalities. One high-grade stenosis was identified by CT/CTA that was expected occluded on MRI/MRA. Two MRI/MRA-confirmed pseudoaneurysms were missed by CT/CTA. None of the controls evidenced specific imaging signs for dissection. CT/CTA is a reliable and better available alternative to MRI/MRA for diagnosis of sCAD. CT/CTA should be used to complement MRI/MRA in cases where MRI/MRA suggests occlusion.


Morphological connectivity correlates with trait impulsivity in healthy adults.
Impulsivity is one crucial personality trait associated with various maladaptive behavior and many mental disorders. In the study reported here, we investigated the relationship between impulsivity and morphological connectivity (MC) between human brain regions, a newly proposed measure for brain coordination through the development and learning. Twenty-four participants' T1-weighted magnetic resonance imaging (MRI) images and their self-reported impulsivity scores, measured by the Barratt impulsiveness scale (BIS), were retrieved from the OpenfMRI project. First, we assessed the MC by quantifying the similarity of probability density function of local morphological features between the anterior cingulate cortex (ACC), one of the most crucial hubs in the neural network modulating cognitive control, and other association cortices in each participant. Then, we correlated the MC to impulsivity scores across participants. The BIS total score was found to correlate with the MCs between the ACC and two other brain regions in the right hemisphere: the inferior frontal gyrus (IFG), a well-established structure for inhibition control; the inferior temporal gyrus (ITG), which has been previously shown to be associated with hyperactive/impulsivity symptoms. Furthermore, the ACC-IFG MC was mainly correlated with motor impulsivity, and the ACC-ITG MC was mainly correlated with attentional impulsivity. Together, these findings provide evidence that the ACC, IFG, and ITG in the right hemisphere are involved neural networks modulating impulsivity. Also, the current findings highlight the utility of MC analyses in facilitating our understanding of neural correlates of behavioral and personality traits.


Keratin hydrolysis by dermatophytes.
Dermatophytes are the most common cause of superficial fungal infections (tinea infections) and are a specialized group of filamentous fungi capable of infecting and degrading keratinised tissues, including skin, hair, and nail. Essential to their pathogenicity and virulence is the production of a broad spectrum of proteolytic enzymes and other key proteins involved in keratin biodegradation and utilization of its breakdown products. The initial stage of biodegradation of native keratin is considered to be sulfitolysis, in which the extensive disulfide bridges present in keratin are hydrolyzed, although some secreted subtilisins can degrade dye-impregnated keratin azure without prior reduction (Sub3 and Sub4). Sulfitolysis facilitates the extracellular biodegradation of keratin by the dermatophytes' extensive array of endo- and exoproteases. The importance of dermatophyte proteases in infection is widely recognized, and these enzymes have also been identified as important virulence determinants and allergens. Finally, the short peptide and amino acid breakdown products are taken up by the dermatophytes, using as yet poorly characterised transporters, and utilized for metabolism. In this review, we describe the process of keratin biodegradation by dermatophytes, with an especial focus on recent developments in cutting edge molecular biology and '-omic' studies that are helping to dissect the complex process of keratin breakdown and utilization.


Intercellular communication of DNA damage and oxidative status underpin bystander effects.
A well-known phenomenon in the field of radiation biology is that cells exposed to ionizing radiation (IR) (targeted cells) can induce in non-irradiated (non-targeted), bystander cells effects reminiscent of DNA damage responses (DDR) normally expected, exclusively in targeted cells. These phenomena are collectively referred to as radiation-induced bystander effects (RIBE) and have different manifestations depending on the endpoint studied. Although it is now recognized that RIBE reflects to a considerable extent communication by the targeted cells to undamaged cells of their damaged status, the molecular underpinnings of this communication and its significance for the organism are only partly understood. In particular, it remains unknown why and how targeted cells induce DNA damage in non-targeted, bystander cells threatening their genomic stability and risking thus their transformation to cancer cells. Here, we outline observations hinting to possible sources of artifacts in experiments designed to detect RIBE and summarize a model according to which targeted cells modulate their redox status as part of their overall response to IR and use this modified redox status as a source to generate signals that are transmitted to non-irradiated cells of the organism. A synthesis of published evidence is presented. Depending on type, RIBE signals may be transmitted through various forms of direct intercellular contact, through molecules acting locally in a paracrine fashion, or through molecules acting remotely in an endocrine fashion. We reason that DNA damage generated in bystander cells is unlikely to manifest the clustered character exhibited in directly exposed cells and postulate that RIBE will depend on complications generated when simpler forms of damage encounter the DNA replication fork. We suggest that RIBE result from intercellular communication mechanisms designed to spread within tissues, or the organism, alarm signals of DNA damage inflicted in subsets of the constituent cells. This response likely evolved to protect organisms by appropriately modulating stress response, repair or apoptosis, and may in some instances also cause adverse effects, e.g. as collateral damage.


Venom-Inspired Medicine: Ancient Chemicals Offer Novel Solutions.
There are an estimated 150,000 animal species that have evolved venom. Some are familiar, such as snakes, bees, scorpions, and spiders. But there are also venomous lizards, sea anemones, cone snails, and even a few mammals, like the duck-billed platypus with its venom-bearing ankle spurs [1].


[The possibilities of adaptation of patients with multiple sclerosis: the results of clinical and psychological study].
A complex clinical and psychological examination of three groups of patients with stable neurological deficit (113 subjects, 77 men and 76 women, aged from 19 to 67 years) included those with multiple sclerosis (MS), chronic cerebral vascular disorders and chronic dorsopathy with illness duration 5-7 years has been carried out. Neuropsychological status and quality of life were assessed using the following tests: Medical Outcomes Study Short Form 36 Health Survey (SF-36); the method of E.B. Fantalova "Level of Ratio of "Values" to "Availability" in Different Life Spheres", Integrative Anxiety Test, Manual for the Constructive Thinking Inventory, Coping test (Lazarus), Beck depression scale. In total, 42 traits on 6 tests have been studied. The study was conducted before and after treatment (21 +/- 2 days). The results revealed that patients with chronic neurological disorders, in particular with MS, often had subclinical depression, which negatively influenced the disease course, and needed treatment. A high level of anxiety was found in MS patients that was related to situational social defensive reaction. Low ability to positive reevaluation of life situations, one of the causes of anxiety states, was observed in all the groups, especially in MS. In MS patients, their real state was not consistent with their perception of this state. They also were featured by personal superstitious thinking. Most of the patients with MS had a good constructive thinking, preserved ability to emotional and behavioral self-control that indicated favorable prognosis in future complex rehabilitation. After the course of symptomatic vascular and metabolic therapy, with the exception of antidepressants and neuroleptics, the appearances of depression and anxiety as well as expression of social defensive reactions and situational phobic component of anxiety were decreased that suggested the necessity of inclusion of individual psychotherapy as a part the complex rehabilitation therapy.


A rapid extraction procedure of human hair proteins and identification of phosphorylated species.
We developed a rapid and convenient extraction procedure of human hair proteins to examine their biochemical properties in detail. This procedure is based upon the fact that the combination of thiourea and urea in the presence of a reductant can effectively remove proteins from the cortex part of human hair. The extracted fraction mainly consisted of hard alpha-keratins with molecular masses of 40-60 kDa, matrix proteins with 12-18kDa, and minor components with 110-115kDa and 125-135kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein phosphorylation in human hair was investigated by immunoblotting with antibodies against phosphoserine, phosphothreonine and phosphotyrosine. We found serine phosphorylation in alpha-keratins and matrix proteins and threonine phosphorylation in alpha-keratins. The extraction was also found to be effective when wool, chicken feathers, rat hair and human nails were used as starting materials.


Dietary Plant Polysaccharides for Cancer Prevention: Role of Immune Cells and Gut Microbiota, Challenges and Perspectives.
Dietary plant polysaccharides, one of the main sources of natural polysaccharides, possess significant cancer prevention activity and potential development value in the food and medicine fields. The anti-tumor mechanisms of plant polysaccharides are mainly elaborated from three perspectives: enhancing immunoregulation, inhibiting tumor cell growth and inhibiting tumor cell invasion and metastasis. The immune system plays a key role in cancer progression, and immunomodulation is considered a significant pathway for cancer prevention or treatment. Although much progress has been made in revealing the relationship between the cancer prevention activity of polysaccharides and immunoregulation, huge challenges are still met in the research and development of polysaccharides. Results suggest that certain polysaccharide types and glycosidic linkage forms significantly affect the biological activity of polysaccharides in immunoregulation. At present, the in vitro anti-tumor effects and immunoregulation of dietary polysaccharides are widely reported in articles; however, the anti-tumor effects and in vivo immunoregulation of dietary polysaccharides are still deserving of further investigation. In this paper, aspects of the mechanisms behind dietary polysaccharides' cancer prevention activity achieved through immunoregulation, the role of immune cells in cancer progression, the role of the mediatory relationship between the gut microbiota and dietary polysaccharides in immunoregulation and cancer prevention are systematically summarized, with the aim of encouraging future research on the use of dietary polysaccharides for cancer prevention.


Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from Falling Precursor Levels and Increased Levels of Oligomeric PrPSc Species.
In lethal prion neurodegenerative diseases, misfolded prion proteins (PrP(Sc)) replicate by redirecting the folding of the cellular prion glycoprotein (PrP(C)). Infections of different durations can have a subclinical phase with constant levels of infectious particles, but the mechanisms underlying this plateau and a subsequent exit to overt clinical disease are unknown. Using tandem biophysical techniques, we show that attenuated accumulation of infectious particles in presymptomatic disease is preceded by a progressive fall in PrP(C) level, which constricts replication rate and thereby causes the plateau effect. Furthermore, disease symptoms occurred at the threshold associated with increasing levels of small, relatively less protease-resistant oligomeric prion particles (oPrP(Sc)). Although a hypothetical lethal isoform of PrP cannot be excluded, our data argue that diminishing residual PrP(C) levels and continuously increasing levels of oPrP(Sc) are crucial determinants in the transition from presymptomatic to symptomatic prion disease. Prions are infectious agents that cause lethal brain diseases; they arise from misfolding of a cell surface protein, PrP(C) to a form called PrP(Sc). Prion infections can have long latencies even though there is no protective immune response. Accumulation of infectious prion particles has been suggested to always reach the same plateau in the brain during latent periods, with clinical disease only occurring when hypothetical toxic forms (called PrP(L) or TPrP) begin to accumulate. We show here that infectivity plateaus arise because PrP(C) precursor levels become downregulated and that the duration of latent periods can be accounted for by the level of residual PrP(C), which transduces a toxic effect, along with the amount of oligomeric forms of PrP(Sc).


Fine-Tuning Window Apertures in ZIF-8/67 Frameworks by Metal Ions and Temperature for High-Efficiency Molecular Sieving of Xylenes.
Separation of structurally similar components from their mixtures is one of the most promising applications of metal-organic frameworks (MOFs). A high efficiency of such molecular sieving requires fine tuning of the MOF structure. In this work, we investigate subtle metal- and temperature-induced changes in window dimensions of zeolitic imidazolate frameworks (ZIF-8(Zn) and ZIF-67(Co)) and apply such structural tuning for efficient separation of xylene isomers (p-, m-, and o-xylenes). The use of Co instead of Zn favorably modifies window geometry: it accelerates the diffusion of all components by a factor of 2-3 while maintaining closely the same separation efficiency as that of ZIF-8(Zn). Outstanding selectivity above 18:1 and faster isolation of demanded p-xylene from the ternary mixture using ZIF-67(Co) have been demonstrated at room temperature, opening new horizons for its energy-efficient xylene separation. More generally, our findings suggest the prospective ways to tune various MOFs for target liquid-state separations.


Effect of noradrenaline on the content, synthesis and catabolism of acetylcholine in the brain.
ACh synthesis and content in the cerebral cortex and brain stem as well as the activity of choline acetylase (AcCh) and acetylcholinesterase (AchE) in brain homogenates were determined after NA administration both in vivo and in in vitro. In in vivo experiments NA was injected intraperitoneally or into the lateral ventricle of the brain. Intraperitoneal injection of NA caused a significant fall of ACh content in the cerebral cortex. AchE activity was inhibited after intraventricular NA injection and in in vitro investigations, in which NA was added into the incubation medium. ACh synthesis and AcCh activity showed no abnormalities after NA administration in vivo and in vitro.


The onset of chaos in the vibrational dynamics of LiNC/LiCN.
Recent advances in vibrational spectroscopy have greatly enhanced the possibilities of research of highly excited states in molecular systems of moderate size. At sufficiently high level of excitation the correspondence principle holds, and classical mechanical arguments constitute a useful interpretative tool. The corresponding dynamics often become very complex specially in systems with floppy degrees of freedom, and periodic motion plays an important role for its understanding. In this paper, we present a computational procedure to systematically calculate periodic orbits of LiNCLiCN with a given symmetry, that has the additional advantage of providing a useful insight into the onset of chaos in this system.


Molecular phylogeny of silk producing insects based on internal transcribed spacer DNA1.
Silk moths are the best studied silk secreting insects and belong to the families Bombycidae and Saturniidae. The phylogenetic relationship between eleven silk producing insects was analyzed using the complete DNA sequence of the internal transcribed spacer DNA 1 locus. The PCR amplification and sequence analysis showed variation in length ranging from 138 bp (Antheraea polyphemus) to 911 bp (Hyalopora cecropia). Microsatellite sequences were found and was be used to distinguish Saturniidae and Bombycidae members. The nucleotide sequences were aligned manually and used for construction of phylogenetic trees based on Maximum parsimony and Maximum likelihood methods. The topology in both the approaches yielded a similar tree that supports the ancestral position of the Antheraea assama.


[RISK-FSCTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA].
The purpose of the research was to study the lipid profile, some indices of hemostasis and cytokine status of rosacea patients with severe climacteric syndrome. Serum lipid profile was studied by means of the following parameters: total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (the study of lipid profile was performed by the device "INTEGRAM +400" (Company "ROSH»). Haemostatic system was evaluated in terms of prothrombin, thrombin time. Content of fibrinogen, fibrinolytic activity, and prothrombin index were determined. The concentration of free VEGF (vascular endothelial growth factor) and IL-8 were measured by ELISA. The results of these studies suggest that the phenomenon of hyper coagulation and disorders in lipid profile of blood serum in patients with rosacea with climacteric syndrome can be considered as risk factors of cardiovascular disease. From the other side, as a powerful provocateur of increased permeability, atony and fragility of vessel walls, VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients.


[Laparoscopic surgery for endometrial cancer in overweight women].
The aim of this study was to investigate the feasibility and safety of laparoscopic staging of overweight women with endometrial cancer and to compare the surgical outcomes among these patients with those managed by laparotomy. This was a retrospective analysis (Canadian Task-force Classification II-3). We reviewed operative and hospital records of 70 patients with a body mass index >25 kg/m2 who underwent surgical treatment for endometrial cancer between 2001 and 2008. Thirty-five patients treated laparoscopically were compared to an equivalent group of patients treated by laparotomy. Operative and postoperative variables were afterwards assessed. Women in laparoscopic group had a significantly lower blood loss (median, 25th-75th percentiles: 1.2, 0.8-2.0 in laparoscopic versus 1.8, 1.0-2.8 in laparotomic group, P<0.05). No differences between both group in terms of operative time (median, 25th-75th percentiles: 165 min, 130-183 in laparoscopic versus 135 min, 110-170 in laparotomic; P>0.05) and mean number of pelvic and para-aortic lymph nodes removed (22 ± 8.4 versus 24 ± 6.2 and 9.2 ± 2.5 versus 9.3 ± 5 respectively; P>0.05). Length of urethral catheter and hospital stay were statistically higher in laparotomic group (two days versus three days; four days versus seven days respectively; P<0.05). Laparoscopic surgery in overweight women with endometrial cancer had equivalent surgical staging than women operated by laparotomy. With regard to postsurgical variables, overweight women who underwent laparoscopic surgery had better results than those treated by laparotomy.


The non-LTR (long terminal repeat) retrotransposon L1Tc from Trypanosoma cruzi codes for a protein with RNase H activity.
The deduced amino acid sequence of the region downstream of the reverse transcriptase (RT) motif of the Trypanosoma cruzi L1Tc non-LTR retrotransposon shows a significant homology with the sequence coding for proteins with RNase H activity from different organisms and retroelements. The 25-kDa His(6)-tagged recombinant protein bearing only the L1Tc RNase H domain, named RHL1Tc, exhibits RNase H activity as measured on the [(3)H]poly(rA)/poly(dT) hybrid used as substrate as well as on specific homologous and heterologous [(32)P]RNA/DNA hybrids. The mutation of the conserved aspartic acid at position 39 of the enzyme catalytic site, but not of the serine at position 56 (non-conservative amino acid), abolishes protein RNase H activity. The RNase H activity of the RHL1Tc protein is Mg(2+)-dependent, and it is also active in the presence of the Mn(2+) ion. The optimal condition of RNase H activity is found at pH 8 and 37 degrees C, although it also has significant enzymatic activity at 19 degrees C and pH 6. However, it cannot be excluded that the RNase H activity level and its optimal conditions may be different from that of a protein containing both RT and RNase H domains.


Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.
Laparoscopic surgery presents a large number of advantages over laparotomy. The goal of this work was to check whether these benefits outweigh any greater risk of complications. The study design was a meta-analysis of published data from prospective randomized clinical trials (RCT). For the period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial Registers and asked the investigators for further details. Meta-analysis was carried out with the Cochrane review manager software RevMan 4.1. A total of 27 prospective RCT including 3611 women (1809 treated by operative laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis. The overall risk of complications was significantly lower for patients operated by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI) 0.50-0.70]. There was no statistically significant difference concerning the risk of major complications with respect to the approach used (RR 1.0; 95% CI 0.60-1.65). The risk of minor complications was significantly lower for patients operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the risks of readmission, second procedure and blood transfusion, there was no difference between the two groups. Identical results were found when we performed a sensitivity analysis including or excluding studies according to the methodological score. Subgroup analysis according to how serious the surgery was (minor, major, advanced) showed a significant increase in the risk of transfusion for advanced procedures performed by laparotomy. Laparoscopic surgery is not inherently dangerous for patients presenting benign gynaecological pathologies. The potential risk of complications should no longer be advanced as an argument against using laparoscopic surgery rather than laparotomy for an operation when the indication allows the choice.


The Social Structure of Mortgage Discrimination.
In the decade leading up to the U.S. housing crisis, black and Latino borrowers disproportionately received high-cost, high-risk mortgages-a lending disparity well documented by prior quantitative studies. We analyze qualitative data from actors in the lending industry to identify the social structure though which this mortgage discrimination took place. Our data consist of 220 depositions, declarations, and related exhibits submitted by borrowers, loan originators, investment banks, and others in fair lending cases. Our analyses reveal specific mechanisms through which loan originators identified and gained the trust of black and Latino borrowers in order to place them into higher-cost, higher-risk loans than similarly situated white borrowers. Loan originators sought out lists of individuals already borrowing money to buy consumer goods in predominantly black and Latino neighborhoods to find potential borrowers, and exploited intermediaries within local social networks, such as community or religious leaders, to gain those borrowers' trust.


Automatic brain matter segmentation of computed tomography images using a statistical model: A tool to gain working time!
Brain computed tomography (CT) is useful diagnostic tool for the evaluation of several neurological disorders due to its accuracy, reliability, safety and wide availability. In this field, a potentially interesting research topic is the automatic segmentation and recognition of medical regions of interest (ROIs). Herein, we propose a novel automated method, based on the use of the active appearance model (AAM) for the segmentation of brain matter in CT images to assist radiologists in the evaluation of the images. The method described, that was applied to 54 CT images coming from a sample of outpatients affected by cognitive impairment, enabled us to obtain the generation of a model overlapping with the original image with quite good precision. Since CT neuroimaging is in widespread use for detecting neurological disease, including neurodegenerative conditions, the development of automated tools enabling technicians and physicians to reduce working time and reach a more accurate diagnosis is needed.


Association of Klotho with physical performance and frailty in middle-aged and older adults: A systematic review.
Ageing is an inevitable process of physical deterioration that impairs functional autonomy and quality of life, becoming a public health issue. Since the percentage of people over 60 years is increasing worldwide, the use of easily detectable biomarkers of ageing is a relevant tool for monitoring of the ageing process and treatment. Among them, Klotho, an ageing suppressor gene because its deficiency leads to ageing like phenotype, seems particularly promising. This systematic review includes the last 10 years clinical studies that evaluated the association between plasma Klotho and body composition, physical performance and frailty in both sedentary and active middle-aged and older adults. Sixteen studies have been found: nine regarding the association between Klotho and body composition, two the association of Klotho and frailty and finally five concerning the effects of physical activity on Klotho. The results of these studies, albeit with some exceptions, point out that Klotho is positively associated with muscle strength and negatively with osteoporosis, frailty, disability and mortality while physical activity generally increases Klotho levels. Moreover, even if there are still few clinical studies, Klotho might be positively associated with bone mineral density, muscle strength, longevity, mobility and robustness during ageing.


Dual-Energy CTA in Patients with Symptomatic Peripheral Arterial Occlusive Disease: Study of Diagnostic Accuracy and Impeding Factors.
Purpose The purpose of this study was to assess the diagnostic performance of dual-energy CT angiography (DE-CTA) in patients with symptomatic peripheral artery occlusive disease (PAOD) and to identify factors that impede its diagnostic accuracy. Materials and Methods Dual-source DE-CTA scans of the lower extremities of 94 patients were retrospectively compared to the diagnostic reference standard, digital subtraction angiography (DSA). Two independent observers assessed PAOD incidence, image quality, artifacts, and diagnostic accuracy of DE-CTA in 1014 arterial segments on axial, combined 80/140 kVp reconstructions and on 3 D maximum intensity projections (MIP) after automated bone and plaque removal. The impact of calcifications, image quality, and image artifacts on the diagnostic accuracy was evaluated using Fisher's exact test. Furthermore, interobserver agreement was analyzed. Results Two observers achieved sensitivities of 98.0 % and 93.9 %, respectively, and specificities of 75.0 % and 66.7 %, respectively, for detecting stenoses of > 50 % of the lower extremity arteries. Calcifications impeded specificity, e. g. from 81.2 % to 46.2 % for reader 1 (p < 0.001). Specificity increased with higher image quality, e. g. from 70.0 % to 76.4 % for reader 1 (p < 0.001). Artifacts decreased the specificity of reader 2 (p < 0.001). The overall interobserver agreement ranged between moderate and substantial for stenosis detection and calcified plaques. Conclusion DE-CTA is accurate in the detection of arterial stenoses of > 50 % in symptomatic PAOD patients. Calcified atherosclerotic plaques, image quality, and artifacts may impede specificity. Key Points: · Sensitivities of DE-CTA were 98.0 and 93.9 %, specificities 75.0 % and 66.7 %.. · Interobserver agreement was moderate to substantial for stenosis and plaque detection.. · Calcified atherosclerotic plaques, image quality, and artifacts may impede specificity.. Citation Format · Klink T, Wilhelm T, Roth C et al. Dual-Energy CTA in Patients with Symptomatic Peripheral Arterial Occlusive Disease: Study of Diagnostic Accuracy and Impeding Factors. Fortschr Röntgenstr 2017; 189: 441 - 452.


Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms.
To demonstrate, in a proof-of-concept study, whether potentiating ipsilesional higher motor areas (premotor cortex and supplementary motor area) augments and accelerates recovery associated with constraint induced movement. In a randomized, double-blinded pilot clinical study, 12 patients with chronic stroke were assigned to receive anodal transcranial direct current stimulation (tDCS) (n = 6) or sham (n = 6) to the ipsilesional higher motor areas during constraint-induced movement therapy. We assessed functional and neurophysiologic outcomes before and after 5 weeks of therapy. Only patients receiving tDCS demonstrated gains in function and dexterity. Gains were accompanied by an increase in excitability of the contralesional rather than the ipsilesional hemisphere. Our proof-of-concept study provides early evidence that stimulating higher motor areas can help recruit the contralesional hemisphere in an adaptive role in cases of greater ipsilesional injury. Whether this early evidence of promise translates to remarkable gains in functional recovery compared to existing approaches of stimulation remains to be confirmed in large-scale clinical studies that can reasonably dissociate stimulation of higher motor areas from that of the traditional primary motor cortices.


Model-based estimation of quantitative ultrasound variables at the proximal femur.
To improve the prediction of the osteoporotic fracture risk at the proximal femur we are developing a scanner for quantitative ultrasound (QUS) measurements at this site. Due to multipath transmission in this complex shaped bone, conventional signal processing techniques developed for QUS measurements at peripheral sites frequently fail. Therefore, we propose a model-based estimation of the QUS variables and analyze the performance of the new algorithm. Applying the proposed method to QUS scans of excised proximal femurs increased the fraction of evaluable signals from approx. 60% (using conventional algorithms) to 97%. The correlation of the standard QUS variables broadband ultrasound attenuation (BUA) and speed of sound (SOS) with the established variable bone mineral density (BMD) reported in previous studies is maintained (BUA/BMD: r(2) = 0.69; SOS/BMD: r(2) = 0.71; SOS+BUA/BMD: r(2) = 0.88). Additionally, different wave types could be clearly detected and characterized in the trochanteric region. The ability to separate superimposed signals with this approach opens up further diagnostic potential for evaluating waves of different sound paths and wave types through bone tissue.


Event-related brain potentials in individuals at high and low risk for developing alcoholism: failure to replicate.
Event-related brain potentials (ERPs) were used to compare young men having a positive paternal family history for alcoholism (FHP) with carefully matched control subjects having no family history for alcoholism (FHN). The P300 ERP component was obtained from all subjects (n = 10/group) with a complex auditory paradigm before and on two occasions after they received a placebo drink which they were told might contain alcohol. The procedures employed replicated those of a previous study in which FHP subjects showed diminished P300 potentials compared to FHN subjects under the placebo as well as ethanol consumption conditions--a finding which raised the possibility that the P300 ERP component might be a biological marker for subjects at high risk to develop alcoholism. No differences between the family history groups were obtained for the P300 or any other ERP component using the replication procedures. Both groups demonstrated a decrease in P300 amplitude across trial blocks in a similar fashion suggesting that habituation effects may have diminished the ERP response.


Functional form of the Parisi overlap distribution for the three-dimensional Edwards-Anderson Ising spin glass.
Recently, it has been conjectured that the statistics of extremes is of relevance for a large class of correlated systems. For certain probability densities this predicts the characteristic large x falloff behavior f(x) approximately exp(-ae(x)), a>0. Using a multicanonical Monte Carlo technique, we have measured the Parisi overlap distribution P(q) for the three-dimensional Edward-Anderson Ising spin glass at and below the critical temperature We find that a probability distribution related to extreme-order statistics gives an excellent description of P(q) over about 80 orders of magnitude.


Optimization of immunohistochemical detection of ERBB2 in human breast cancer: impact of fixation.
In an attempt to standardize the immunohistochemical detection of ERBB2, we evaluated six normal breast samples and 58 breast carcinomas for (1) the effect of four different fixatives (Bouin's fluid, buffered formalin, alcoholic formalin, and methacarn), and (2) the sensitivity and specificity of eight commercially available antibodies. ERBB2 gene copy numbers and RNA transcripts were measured by Southern and Northern blot analysis in all samples. The BT-474 and MCF7 cell lines were processed in the same way as the tissue samples and used a s references of activation or the normal state of the ERBB2 gene, respectively. Complete concordance between immunohistochemistry and molecular biology was observed in 43/58 cases (74 per cent). However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants. The most consistent results were obtained with NCLCB11 on frozen sections and with Tab250 on paraffin-embedded sections. For prospective studies, the use of alcoholic formalin in association with a highly specific antibody (Tab250, 9G6, NCLCB11, or OA-11-854) gave the best results. Methacarn appears to be a reliable fixative, but was studied in only 28 cases. For retrospective studies, the most important parameter to take into account is the sensitivity of the antibody. Thus, with Bouin's fixation, 3B5 was the only reliable antibody, whereas with buffered formalin, Tab250 gave the most consistent results. This study will help inter-laboratory comparisons, and in determining the prognostic significance of ERBB2 expression in breast carcinomas using a standardized methodology.


The biophysical characterization of the first SCN5A mutation R1512W identified in Chinese sudden unexplained nocturnal death syndrome.
Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease. To test our hypothesis that slight acidosis conditions may contribute to the significant loss of function of mutant cardiac sodium channels underlying SUNDS, the biophysical characterization of SCN5A mutation R1512W was performed under both extracellular and intracellular slight acidosis at pH 7.0. The cDNA of R1512W was created using site-directed mutagenesis methods in the pcDNA3 plasmid vector. The wild type (WT) or mutant cardiac sodium channel R1512W was transiently transfected into HEK293 cells. Macroscopic voltage-gated sodium current (INa) was measured 24 hours after transfection with the whole-cell patch clamp method at room temperature in the HEK293 cells. Under the baseline conditions at pH 7.4, R1512W (-175 ± 15 pA/pF) showed about 30% of reduction in peak INa compared to WT (-254 ± 23 pA/pF, P < 0.05). Under the acidosis condition at pH 7.0, R1512W (-130 ± 17 pA/pF) significantly decreased the peak INa by nearly 50% compared to WT (-243 ± 23 pA/pF, P < 0.005). Compared to baseline condition at pH 7.4, the acidosis at pH 7.0 did not affect the peak INa in WT (P > 0.05) but decreased peak INa in R1512W (P < 0.05). This initial functional study for SCN5A mutation in the Chinese SUNDS victim revealed that the acidosis aggravated the loss of function of mutant channel R1512W and suggested that nocturnal sleep disorders-associated slight acidosis may trigger the lethal arrhythmia underlying the sudden death of SUNDS cases in the setting of genetic defect.


Serial office-based steroid injections for treatment of idiopathic subglottic stenosis.
Current treatment options for idiopathic subglottic stenosis include endoscopic interventions, resection, and tracheotomy. Recently, serial office-based steroid injections were proposed as an alternative that may stabilize or induce regression of airway stenosis without the need for repeated operations. Procedure completion rate, pain, complications, effect on stenosis, time since the last operation, and limitations have not been described. Retrospective case series. Retrospective series of 19 patients undergoing serial office-based steroid injection for idiopathic subglottic stenosis. Outcome measures included completion rate, procedure-related pain scores, complications, percentage of airway stenosis, and time since the last operative intervention. Procedure completion rate was 98.8%. Average pain score during the procedure was 2.3 ± 1.7 on a 10-point scale. There were no immediate complications. One patient underwent awake tracheotomy 8 days after her second injection and was later decannulated. Average stenosis decreased from 35% ± 15% to 25% ± 15% (n = 16; P = .086) over the first of three injections and 40% ± 15% to 25% ± 10% to 20% ± 10% (n = 8; P = .002) for those patients completing two sets of three injections. Fourteen of 17 patients undergoing at least three injections have not returned to the operating room since the first injection. Office-based steroid injection represents a promising new treatment pathway for a disease that requires long-term management, offering a purely pharmacologic approach to a disorder that has traditionally been approached from a mechanical perspective. It is safe, well tolerated, and effective. Furthermore, it may help patients and physicians avoid repeated trips to the operating room and the associated risks. 4. Laryngoscope, 127:2475-2481, 2017.


[Complete androgen blockade (orchiectomy + flutamide) versus androgen blockade with cytostasis (orchiectomy + estramustine) in the treatment of virginal advanced prostate cancer].
The results of orchiectomy + flutamide (n = 28) versus orchiectomy + estramustine (n = 27) in the initial therapy of advanced prostatic cancer were compared in a prospective randomized study. The minimum observation period was one year. In the group orchiectomy + flutamide the incidence of side effects was 25%, the response rate (complete + partial remission) was 28% and the progression rate was 18%. 5 patients (18%) died within the first year. In the group orchiectomy + estramustine the incidence of side effects was 22%, the response rate (complete + partial remission) was 29% and the progression rate was 33%. 2 patients (7%) died within 1 year of treatment. There is no significant difference either in the response rate or the progression rate between the two groups.


[Effect of emergency care simulator combined with problem-based learning in teaching of cardiopulmonary resuscitation].
To evaluate the teaching effects of emergency care simulator (ECS) combined with problem-based learning (PBL) in teaching of cardiopulmonary resuscitation (CPR). 42 medical students were randomly divided into 2 equal groups, control group receiving PBL and training of specific operation such as artificial respiration, external cardiac compression, tracheal intubation, and defibrillation, and ECS group receiving ECS training in addition. Then test was given to record the scores in artificial respiration. A questionnaire survey was conducted to collect the feedback. There were no significant differences in the scores of artificial respiration, external cardiac compression, tracheal intubation, and defibrillation between the 2 groups (all P > 0.05). There were significant differences between the Control group and the ECS group (P < 0.05). The percentages of students with enhanced emergency awareness, emergency skill, team spirit and cooperative effort, with improved analytic skill in clinical setting and in amalgamating the theoretic learning with textbook knowledge and clinical practice were all higher in the ECS group than in the control group (all P < 0.05). More than 86% of the students considered that there was significant difference between these two groups. Using ECS combined with PBL in teaching CPR technique directly involves the medical students in "emergency practice", resolving of "all sorts of problems", enhancing emergency awareness, and emergency skill. It can improve teaching quality significantly that is in accordance with the development of modern medicine.


Hypoxic regulation of mRNA expression.
Many tumors are hypoxic, and cells that are experimentally rendered hypoxic display a variety of phenotypes which allow them to adapt to the micro-environment. These phenotypes include a shift from aerobic to anaerobic metabolism, a diminution of reactive oxygen species, an arrest of proliferation, apoptosis, and a secretion of pro-angiogenic growth factors. Some of these hypoxic phenotypes are re-capitulated in normoxic tumor cells (e.g., an increase in anaerobic metabolism), and some tumors have undergone mutations that allow them to bypass the cell cycle arrest and apoptosis typically seen in hypoxic cells. Hypoxic regulation of gene expression is responsible for many hypoxia-induced phenotypes, and here we review a variety of mechanisms by which gene expression is altered in hypoxic cells. These include transcription by HIF-1, the hypoxia inducible transcription factor, and other hypoxia-inducible transcription factors, including ones generated by hypoxic activation of the integrated stress response. Recent data from our laboratory demonstrate that nonsense mediated RNA decay is also regulated in hypoxic cells and thus may play an important role in hypoxic gene regulation and hypoxic phenotypes.


[Treatment of bone and soft tissue defects in the distal part of the shank].
Important loss of tissue in the distal third of the leg sets a difficult problem in reconstruction. The first case gives an example of a free vascularized bone graft, the second of application of the dorsalis pedis flap as an island. The indications are discussed and some points of the operative procedure are mentioned.


The effects of bundling on infant temperature.
To determine whether bundling elevates rectal and/or skin temperature of young infants. Randomized, prospective study stratified by age. Clinical Studies Center at a teaching hospital in Los Angeles. Sixty-four well, full-term infants (ages 11 to 95 days). Control infants (n = 28) were dressed in a disposable diaper and terry coveralls. Bundled infants (n = 36) were dressed as control infants, plus a cap, a receiving blanket, and a thermal blanket. All infants were monitored in an open crib (room temperature 72 degrees to 75 degrees F). Rectal and skin (anterior mid-lower leg) temperatures and infant states were measured at 5-minute intervals from time 0 to 60 minutes and at 62 and 65 minutes. The mean skin temperature of bundled infants increased by 2.67 degrees C/hr; mean rectal temperature increased by 0.06 degrees C/hr. The mean skin temperature of nonbundled infants increased by 1.5 degrees C/hr; mean rectal temperature decreased by less than 0.01 degree C/hr. Comparing bundled infants to nonbundled controls, there was a significant rise in skin temperature (P = .0001) but not in rectal temperature (P > .05, Wilcoxon rank sum test). The study had a power > 98% to detect a rise of .5 degrees C in rectal temperature over 60 minutes. The 95% confidence interval for the change in rectal temperature in bundled infants was -0.03 to +0.15 degrees C. Bundling a healthy infant in a temperate external environment causes an increase in skin temperature, but not in rectal temperature. Elevated rectal temperatures should therefore, rarely if every be attributed to bundling.


Preexisting histologic evidence of prostatitis is unrelated to postimplant urinary morbidity.
The presence and extent of prostatitis on the patients' preimplant biopsy slides was correlated with their postimplant course to determine if any relationship exists between histological prostatitis and postimplant morbidity. Biopsy slides from 56 patients treated with I-125 (144 Gy, TG-43), Pd-103 (125 Gy, NIST-1999), or Pd-103 plus supplemental external beam radiation (20-44 Gy) were studied. As part of ongoing prospective protocols, treatment-related morbidity is monitored by mailed questionnaires at 1, 3, 6, 12, and 24 months postimplant, using standard American Urologic Association (I-PSS) and Radiation Therapy Oncology Group criteria. Patient's preimplant biopsies, stained with standard hematoxylin and eosin, were retrieved for review by one uropathologist (LT). Separate evaluations of the degree and extent of inflammation in biopsy cores free of cancer and in cancerous biopsy cores were undertaken. Infiltrates were classified as periglandular if they were within 50 microns of a glandular structure. They were otherwise classified as stromal. Distribution of the inflammation was reported as focal, multifocal, or diffuse. The intensity of inflammation was separately graded as mild if there were fewer than 10 inflammatory cells per high-power field, moderate if there were 10-200 cells per high-power microscopic field, or severe if there were more than 200 cells per field. In all cases the great majority of inflammatory cells were mononuclear, predominantly lymphocytes. Periglandular inflammation was most common, with 18% of patients having focal periglandular and 20% having multifocal periglandular inflammation on their preimplant biopsies. Cancer-related infiltrates were the second most common, with 23% of patients having focal, 13% multifocal, and 13% diffuse cancer-related inflammation on their preimplant biopsies. Eight of the 55 patients developed postimplant urinary retention, requiring catheterization for 2 to 8 days. The overall incidence of postimplant urinary retention was low and there was no obvious relationship between the presence of inflammation on preimplant biopsy and the likelihood of postimplant urinary retention. AUA score changes at 1 and 6 months postimplant were highly variable and unrelated to the presence or severity of periglandular or cancer-related inflammation. Considering the apparent lack of relationship between histological findings and clinical outcomes in the patients reported here, the authors conclude that histologic evidence of prostatitis is not a contraindication to brachytherapy.


Development and validation of an economical uric acid-Fe3+/Fe2+-ferrozine-based colorimetric assay to estimate uric acid level of pure and biological samples.
This work presents the development and validation of a simple, rapid, and cost-effective spectrophotometric method for quantitative analysis of uric acid in biological samples. The method relies upon uric acid-led reduction of Fe(III) to Fe(II) of sample/standard solutions which stoichiometrically engages ferrozine to form a magenta-colored complex. Different parameters including pH, metal and chelator concentrations, temperature, etc., were optimized for the maximum intensity and stability of the complex. The uric acid concentrations of synthetic/plasma solutions were determined by comparing the color intensity of Fe(ferrozine)3 2+ complex produced by test solution with the standard curve formed by known uric acid concentrations. The method was validated in accordance with ICH guidelines and subjected to human plasma analysis. The results obtained were compared with a reference (enzymatic) method which revealed that there was no significant difference between the two methods at 95% confidence level. The method is highly specific, precise, linear, accurate, and robust.


De Novo Psychiatric Disorders in a Woman With Giant Prolactinoma Treated With Cabergoline.
Dopamine agonists are the first-line treatment of prolactinomas. The risk of developing de novo psychiatric symptoms during dopamine agonist therapy is low. Herein, we report the case of a 42-year-old woman with a giant prolactinoma who developed a psychiatric disorder after 1 day of cabergoline therapy initiation. She presented with amenorrhea, galactorrhea, headaches, and disturbed vision. Biological investigations revealed hyperprolactinemia (2975 ng/ml) with gonadotropin deficiency. Pituitary MRI showed a giant pituitary adenoma. The patient was treated with cabergoline at the dose of 1 mg twice weekly. One day after the treatment initiation, she developed acute delirium with temporospatial disorientation and compulsive medication use. These symptoms disappeared 1 week after the reduction of the dose of cabergoline. Patients with hyperprolactinemia receiving an initial high dose of cabergoline may develop changes in mood and behavior regardless of prior psychiatric history.


Is there a place for intra-umbilical oxytocin for the management of retained placenta?
Intra-umbilical injection of oxytocin has been used to hasten placental separation in retained placenta. A randomised controlled trial was done on 35 consequent women who fulfilled the criteria for retained placenta at the Department of Obstetrics & Gynaecology Ipoh Hospital. Nineteen patients who were recruited into the study group received intraumbilical injection of 301U oxytocin in 27mls saline. Another 16 patients who were in the control group received 30mls of 0.9% sodium chloride (placebo). The primary outcome measured was the need for manual removal of placenta (MRP). Nine out of the 19 patients in the oxytocin group required MRP while 10/16 in the control group required MRP. There was a 24% reduction (95% C.I. 0.41 to 1.39) in the need for MRP in the study group compared to the saline group. our results indicate that intra-umbilical vein injection of oxytocin is not clinically useful for the removal of a retained placenta.


In Vitro and In Vivo Evaluation of GSK-3 Radioligands in Alzheimer's Disease: Preliminary Evidence of Sex Differences.
Glycogen synthase kinase-3 (GSK-3) is a positron emission tomography (PET) imaging target with implications in the pathogenesis of Alzheimer's disease (AD). This preliminary study evaluates human AD and transgenic P301L mouse brain tissues using the GSK-3-targeting radiotracers [3H]PF-367 and [3H]OCM-44 in radioligand binding assays. A saturation analysis showed decreased GSK-3 density in female human AD compared to a normal healthy brain. Equivalence in density (B max), affinity (K d), and apparent affinity (K i) of both radiotracers was demonstrated to enable their interchangeability for in vitro evaluations of GSK-3 expression. An evaluation of P301L mouse brain by [3H]/[11C]OCM-44 delineated differences in the B max of GSK-3 between the control and transgenic mice within male subjects. PET imaging showed similar trends to those observed in vitro. Sex differences are revealed as a potential parameter to consider in the development of GSK-3-targeted diagnostics and therapeutics and could guide recruitment for clinical studies.


Spectroscopy of the A(1B2)-X(1A1) transition of jet-cooled fluorobenzene: laser-induced fluorescence, dispersed fluorescence, and pathological Fermi resonances.
A detailed study of the S1((1)B2)-S0((1)A1) electronic transition of jet-cooled fluorobenzene has been carried out using laser-induced fluorescence and dispersed fluorescence (DF) spectroscopies. Analysis of over 40 single vibronic level DF spectra resulted in the assignment of 16 fundamental frequencies in the excited electronic state. Progressions in totally symmetric modes, particularly in the ring-breathing mode nu9, feature in both types of fluorescence spectrum. There is also significant activity in non-totally-symmetric modes, with activity in Franck-Condon (FC)-allowed overtones, FC-forbidden combinations induced by Duschinsky mixing, and symmetry-forbidden transitions induced by the same Herzberg-Teller vibronic coupling mechanism that induces the benzene S1-S0 transition. Fermi resonances (FRs) are extensive throughout the spectrum, especially in the important FC-active a1 modes. A consequence of these extensive FRs is that several important previous assignments are shown to be incorrect and have been reassigned here. Ab initio and density functional theory calculations have also been performed to support the experimental assignments.


Survey assessment of HIV pre-exposure prophylaxis availability in student health services in New England colleges and universities.
Objective: To determine HIV pre-exposure prophylaxis (PrEP) availability at student health services (SHS) in New England. Methods: We conducted an electronic survey of medical directors of SHS at New England colleges and universities. We measured the availability and volume of PrEP prescribing, barriers and facilitators to prescribing and provider knowledge. Results: Of 143 institutions surveyed, 39% completed questionnaires; 75% were private and 93% were 4 years. Thirty-six percent of institutions did not offer PrEP. Those offering PrEP started a mean of 2.0 per 1000 students/year. PrEP was available at more schools with higher vs. lower endowments (100 vs. 38%, p = 0.002), 4- vs. 2-year programs (68 vs. 0%, p = 0.042), and private vs. public schools (73 vs. 38%, p = 0.043). Conclusions: PrEP was not available at one in three New England SHS and prescribing rates at institutions that offered PrEP were low. Interventions are needed to improve PrEP access.


Instrumented posterior lumbar interbody fusion for patients with degenerative lumbar scoliosis.
Surgery for degenerative lumbar scoliosis remains challenging for spine surgeons even with the application of pedicle screw instrumentation. This retrospective study assesses the outcomes of instrumented posterior lumbar interbody fusion (PLIF) for degenerative lumbar scoliosis. From April 2000 to April 2004, 26 patients with degenerative lumbar scoliosis were treated with instrumented PLIF. Mean age of the 15 females and 11 males was 64.2 years (range, 51 to 77 y). Clinical and radiographic outcomes were retrospectively reviewed for each case at a minimum follow-up of 2 years (median follow-up, 3 y; range, 2 to 6 y). At final follow-up, patients were classified as "satisfied" or "dissatisfied" according to self-reported outcomes. At most recent follow-up, the average Oswestry Disability Index score was significantly lower than the preoperative score (25.8 vs. 58.0; P<0.001). Twenty (76.9%) patients reported that they were satisfied with their surgical outcomes. The average lumbar scoliosis angles were significantly less than preoperative angles (7.4 vs. 16.5 degrees; P<0.001), resulting in a reduction in mean scoliosis angles of 55.2%. The average angles of lumbar lordosis were significantly higher than preoperative angles (30.1 vs. 22.2 degrees; P=0.001), an increase in mean lumbar lordosis angles of 35.6%. No perioperative deaths or major medical complications occurred. Five patients had adjacent segment degeneration and 4 (80%) of 5 reported dissatisfactory outcomes. Further study is required to identify the etiologies of adjacent segment degeneration and methods for avoiding such degeneration. Analytical results demonstrate that instrumented PLIF after laminectomy in patients with degenerative lumbar scoliosis is an effective and safe procedure.


Airborne gamma spectrometry--towards integration of European operational capability.
Airborne gamma spectrometry is an excellent tool for finding out in a timely manner the extent and magnitude of the dispersion of radioactive materials resulting from a nuclear disaster. To utilise existing European airborne monitoring capabilities for multilateral assistance in an accident is a complex administrative and technical matter. Several international exercises have been organised demonstrating the capability to cooperate. However, efficient mutual assistance between European countries requires conceptual work, standards and harmonisation of software. A unified radiological vocabulary and data exchange format in XML need to be developed. A comprehensive database is essential for data assimilation. An operations centre is needed for management and planning of surveys.


DNA methylation and developmental genes in lymphomagenesis--more questions than answers?
There is now considerable evidence suggesting that alterations in the DNA methylating machinery play an important role in tumorigenesis and tumour progression. For example, focal hypermethylation and generalised genomic demethylation are features of many different types of neoplasms. It is thought that tumorigenesis and tumour progression may be caused by hypermethylation induced mutational events and silencing of genes which control cellular proliferation and/or demethylation induced reactivation of genes which may only be required during embryological development. Consequently, we have begun to investigate the role of DNA methylation and developmental genes in malignant lymphoproliferative diseases. Previously, in all cases of non-Hodgkins lymphoma and leukemia studied, we have shown that the myogenic developmental gene Myf-3 is abnormally hypermethylated. In this review we discuss the possible significance of these findings since in vitro studies suggest that Myf-3 may play an important role in control of the cell cycle and therefore lymphomagenesis. In vitro and in vivo evidence suggests that PAX genes may also have oncogenic potential. The PAX family of developmental genes are involved in cellular differentiation, proliferation and cell migration. Expression of PAX3 in particular is associated with cellular mobility. Our previous studies have indicated that alternate regional expression of PAX genes may be controlled by DNA methylation. Therefore, we have proposed that abnormal methylation profiles of PAX3 may be associated with neoplastic transformation and/or metastatic potential. Results thus far reveal that the paired box of PAX3 is abnormally hypermethylated and the homeobox abnormally hypomethylated in lymphomas and leukemias. These new findings are consistent with our postulate and support the idea that inappropriate methylation induced activation or inactivation of developmental genes such as Myf-3 and PAX3 play an important role in lymphomagenesis and disease progression and that inspection of the methylation status of other developmental genes is warranted.


[Effects of insulin on the deformability of normal erythrocytes suspended on artificial tampons, in normal plasma and plasma of diabetic patients].
The effect of different insulin concentrations on the deformability of normal red blood cells resuspended in different media was studied in vitro. Insulin enhances red blood cell deformability measured by the filtration method and the observed increases are directly correlated with insulin concentrations. When red blood cells are resuspended in plasma of diabetic patients, the red blood cell filterability through Nucleopore filters is slower than that observed by resuspending the erythrocytes in normal plasma. This suggests that the plasma of diabetic patients contains an unknown factor able to reduce red blood cell deformability.


Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer.
PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested case-control study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.


Short-term Impact of Meaningful Use Stage 1 Implementation: A Comparison of Health Outcomes in 2 Primary Care Clinics.
We studied a primary care clinic transitioning to Meaningful Use stage 1 and a comparison clinic within the same health system. In the 6 months following implementation, after adjusting for confounders, mean systolic blood pressure worsened (+3.3 mm Hg; P = .004) in the intervention clinic compared with the comparison clinic. We did not see a change in the mean or proportion of patients meeting target goals for diabetes (hemoglobin A1c) or obesity (body mass index). Our findings suggest that the worsening of systolic blood pressure associated with Meaningful Use implementation is likely due to distractions of system changes negatively impacting health outcomes.


Multisequence MRI-based radiomics model for predicting POLE mutation status in patients with endometrial cancer.
Preoperative identification of POLE mutation status would help tailor the surgical procedure and adjuvant treatment strategy. This study aimed to explore the feasibility of developing a radiomics model to pre-operatively predict the pathogenic POLE mutation status in patients with EC. The retrospective study involved 138 patients with histopathologically confirmed EC (35 POLE-mutant vs 103 non-POLE-mutant). After selecting relevant features with a series of steps, three radiomics signatures were built based on axial fat-saturation T2WI, DWI, and CE-T1WI images, respectively. Then, two radiomics models which integrated features from T2WI + DWI and T2WI + DWI+CE-T1WI were further developed using multivariate logistic regression. The performance of the radiomics model was evaluated from discrimination, calibration, and clinical utility aspects. Among all the models, radiomics model2 (RM2), which integrated features from all three sequences, showed the best performance, with AUCs of 0.885 (95%CI: 0.828-0.942) and 0.810 (95%CI: 0.653-0.967) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses indicated that RM2 had improvement in predicting POLE mutation status when compared with the single-sequence-based signatures and the radiomics model1 (RM1). The calibration curve, decision curve analysis, and clinical impact curve suggested favourable calibration and clinical utility of RM2. The RM2, fusing features from three sequences, could be a potential tool for the non-invasive preoperative identification of patients with POLE-mutant EC, which is helpful for developing individualized therapeutic strategies. This study developed a potential surrogate of POLE sequencing, which is cost-efficient and non-invasive.


[An outline of the history of neuroendoscopy].
Almost 200 years ago, German doctor Philipp Bozzini introduced the idea of endoscopy as a method of permitting visualisation of body cavities through their natural openings. First experiences with the use of this new method in different fields of medicine began in the early 20th century. Development of neuroendoscopy was related to the treatment of hydrocephalus. In 1910 Victor Lespinasse conducted the first neuroendoscopic intervention. He executed coagulation of choroid plexus in two children diagnosed with communicating hydrocephalus. The method was further developed by Walter Dandy who implemented ventriculography, worked out by himself in 1918, into the procedure of choroid plexus removal in hydrocephalic patients. For many, he is considered the father of neuroendoscopy. In 1923, William Mixter executed the first successful endoscopic ventriculostomy of the third ventricle. Spinal endoscopy began in the 1930's, but did not excite such interest as intracranial interventions. Introduction of the so-called shunt surgery for the treatment of hydrocephalus and application of operating microscopes in neurosurgery delayed progress of neuroendoscopy. It was not until the technical advances in optics and related fields of physics, that the neuroendoscopy resurged and has added a new dimension to neurosurgery. In 1963 GBrard Guiot described widespread possibilities of using endoscope in neurosurgery. In 1966 Harold Hopkins applied solid rod lenses in the construction of the endoscope, bringing it to its current standard of excellence. The introduction of the neurofiberoscope in 1973 by Takanori Fukushima opened further possibilities in the field of neuroendoscopy. The renaissance of endoscopy observed nowadays results from a general intention to limit invasiveness in neurosurgery.


Effect of absorbable gelatin sponge in the middle ear: in vitro and in vivo animal model.
GelitaSpon gelatin sponge (GS) showed faster reabsorption than gelfoam (GF) in vitro, and GS-packed middle ears resulted in a faster hearing recovery and less inflammation than the ears packed with GF soaked in saline. Soaking GF sponges with boric acid (BA) appeared to offset the inflammatory response of saline-soaked GF, making this inflammatory response comparable to that of GS-packed ears. To describe the reabsorption and inflammatory effects of absorbable gelatin sponge in the middle ear. For in vitro evaluation, GF and GS were used as disks immersed in saline solution or 3% BA and placed in gel. Images were captured with a microscope and processed using image processing Toolbox. For in vivo tests, 16 female albino Sprague Dawley rats were divided into four groups: bulla opening; GF + 0.9% saline; GF + BA; and GS + 0.9% saline. An anterior approach to the right bulla was used for surgery. Preoperative and postoperative auditory brainstem response thresholds were measured. In vitro, there was marked degradation of GF by day 14, while GS showed complete degradation by the third day. In vivo, hearing recovery occurred by day 21. GF produced a more severe inflammatory response, which could be reduced by treating the GF with BA.


Effect of switching medically vulnerable patients with uncontrolled diabetes from isophane insulin human to insulin glargine.
The purpose of this observational study was to determine if switching from isophane insulin human (NPH) to insulin glargine would improve glycemic control in a medically vulnerable population with uncontrolled diabetes. A retrospective cohort review of patients' medical records was performed that recorded events occurring between January 1, 2001, and December 31, 2003. The cohort consisted of patients with diabetes in an adult medicine clinic at a county hospital. Patients were included if they were receiving NPH insulin for a minimum of six months and subsequently switched to insulin glargine for a minimum of six months. The study included 43 patients. There was no significant difference in mean glycosylated hemoglobin (HbA(1c)) between NPH insulin (9.6%) and insulin glargine (9.7%) regimens (p = 0.78, 95% confidence interval, -0.62%, 0.82%). Neither was there a significant difference in the frequency or severity of hypoglycemic episodes between the two treatments. Patients experienced significantly fewer diabetes-associated visits over six months while on insulin glargine. Refill frequency did not differ significantly when patients were receiving NPH insulin versus insulin glargine. When analyzing patient characteristics, those of Hispanic ethnicity experienced HbA(1c) values significantly higher than white patients. Several characteristics were associated with refill frequency. The results of our study indicate that both NPH- and glargine-based basal insulin regimens result in similar levels of glycemic control in a medically vulnerable population with diabetes, without significant differences in the number or severity of hypoglycemic episodes or in refill frequency.


Distribution and feeding habitat characterization of whale sharks Rhincodon typus in a protected area in the north Caribbean Sea.
The relationship between the distribution of the whale shark Rhincodon typus and hydrobiological variables in the Caribbean Sea during 2005-2009 was analysed. Monthly trips were made to the R. typus aggregation area during the months when this species is present in the region (May to September) to record sightings and hydrological data and to collect samples to determine nutrients, chlorophyll a (Chl a) and zooplankton biomass. A total of 2104 R. typus were counted and three zones of high abundance were identified: Cabo-Catoche, Contoy (both within the Whale Shark Biosphere Reserve, WSBR) and the zone knows as Afuera. The zones of greatest R. typus density within the WSBR were characterized by high Chl a concentrations (median: 1·1 mg m-3 , interpercentile range: 0·5-1·8 mg m-3 ) and high nutrient concentrations, such as ammonium (median: 2·5 µmol l-1 , interpercentile range: 0·5-6·4 µmol l-1 ), due to the influence of local upwelling. A generalized additive model (GAM) was used to explore the relationship between R. typus distribution and the environmental variables inside WSBR. Zooplankton biomass was the most influential environmental variable, supporting the close relationship between R. typus distribution and biological productivity. Copepods were the dominant zooplankton group within the WSBR. In the Afuera zone, there were large R. typus aggregations (>80 individuals) associated with zooplankton dominated by fish eggs and significantly higher mean ± s.d. biomass (3356·1 ± 1960·8 mg m-3 ) compared with that recorded inside the WSBR (103·5 ± 57·2 mg m-3 ). The differences among zones generated changes in R. typus distribution patterns and provided opportunities to develop local management strategies for this species.


Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers.
Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm a predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. We collected an additional 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous (p < 0.001) and as discrete variable (10% cut-off: p < 0.003; Immunoreactive score: p < 0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the combined dataset, combining data of new validation cohort with the previously published cohort, showed that AR < 10% significantly correlates with worse outcomes (p = 0.005 for Progression Free Survival (PFS) and p = 0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the combined dataset did not show any statistically significant difference. We confirmed AR loss as predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients' prognosis.


Hematological Values of Healthy Adult Population Living at Moderate Altitude (1869 m, Erzurum, Turkey).
In this study, the normal hematological values in healthy adults living in Erzurum area in Turkey at moderate altitude (1869 m above sea level), and the effect of moderate altitude on these hematological values was investigated. The study population comprised of 929 females and 1204 males aged between 17-95. The mean values for red blood cell and leukocyte counts, and hemoglobin level were significantly higher in males than in females (p<0.0001), whereas platelet count was significantly higher in females than in males (p<0.0001). ›n conclusion, we could not find an increase in the number of red blood cells as well as other hematological parameters in healthy adults living in Erzurum area. Hematological values in this study were similar to those reported in the previous studies carried out with those living under 1869 m.


DNA Topoisomerases.
DNA topoisomerases are enzymes that control the topological state of DNA in all cells; they have central roles in DNA replication and transcription. They are classified into two types, I and II, depending on whether they catalyze reactions involving the breakage of one or both strands of DNA. Structural and mechanistic distinctions have led to further classifications: IA, IB, IC, IIA, and IIB. The essence of the topoisomerase reaction is the ability of the enzymes to stabilize transient breaks in DNA, via the formation of tyrosyl-phosphate covalent intermediates. The essential nature of topoisomerases and their ability to stabilize DNA breaks has led to them being key targets for antibacterial and anticancer agents. This chapter reviews the basic features of topoisomerases focussing mainly on the prokaryotic enzymes. We highlight recent structural advances that have given new insight into topoisomerase mechanisms and into the molecular basis of the action of topoisomerase-specific drugs.


A double Gerdien instrument for simultaneous bipolar air conductivity measurements on balloon platforms.
A bipolar air conductivity instrument is described for use with a standard disposable meteorological radiosonde package. It is intended to provide electrical measurements at cloud boundaries, where the ratio of the bipolar air conductivities is affected by the presence of charged particles. The sensors are two identical Gerdien-type electrodes, which, through a voltage decay method, measure positive and negative air conductivities simultaneously. Voltage decay provides a thermally stable approach and a novel low current leakage electrometer switch is described which initiates the decay sequence. The radiosonde supplies power and telemetry, as well as measuring simultaneous meteorological data. A test flight using a tethered balloon determined positive (sigma(+)) and negative (sigma(-)) conductivities of sigma(+)=2.77+/-0.2 fS m(-1) and sigma(-)=2.82+/-0.2 fS m(-1), respectively, at 400 m aloft, with sigma(+)sigma(-)=0.98+/-0.04.


Mechanisms of induction of regulatory B cells in the tumour microenvironment and their contribution to immunosuppression and pro-tumour responses.
The presence of tumour-infiltrating immune cells was originally associated with the induction of anti-tumour responses and good a prognosis. A more refined characterization of the tumour microenvironment has challenged this original idea and evidence now exists pointing to a critical role for immune cells in the modulation of anti-tumour responses and the induction of a tolerant pro-tumour environment. The coordinated action of diverse immunosuppressive populations, both innate and adaptive, shapes a variety of pro-tumour responses leading to tumour progression and metastasis. Regulatory B cells have emerged as critical modulators and suppressors of anti-tumour responses. As reported in autoimmunity and infection studies, Bregs are a heterogeneous population with diverse phenotypes and different mechanisms of action. Here we review recent studies on Bregs from animal models and patients, covering a variety of types of cancer. We describe the heterogeneity of Bregs, the cellular interactions they make with other immune cells and the tumour itself, and their mechanism of suppression that enables tumour escape. We also discuss the potential therapeutic tools that may inhibit Bregs function and promote anti-tumour responses.


OSTEODENSITOMETRY AND TOMOGRAPHIC FINDINGS IN FOUR CAPTIVE GIANT SOUTH AMERICAN TURTLES (PODOCNEMIS EXPANSA) WITH METABOLIC BONE DISEASE.
Giant South American turtles (Podocnemis expansa) are at a risk of extinction because of the rapid decline in their population over the last few decades. Metabolic bone disease (MBD) is common in captive testudines, but is often not diagnosed until a later stage. The authors present the cases of four captive giant South American turtles with carapace deformity secondary to MBD that underwent computed tomography (CT) scans of the carapace bones and vertebral column. Findings indicative of changes in geometry were found in both. The cancellous bone pattern was characterized by varying degrees of increased trabecular spacing and cortical thinning of the pleural bones. Bone densitometry analysis of the pleural and neural bones and at the level of the body of the third, fourth, and fifth dorsal vertebrae showed mean density values much lower than those found in two adult specimens of the same species that were considered healthy. In conclusion, CT contributed important information on the degree of demineralization and possible structural changes due to MBD and should be considered a relevant tool for diagnosis of this condition.


Strabismus surgery in ocular myasthenia gravis.
We evaluated the efficacy of eye muscle surgery in 4 patients with ocular myasthenia gravis with troublesome diplopia. All patients were in remission and had shown a consistently stable angle of deviation for at least 6 months preoperatively. The extent of eye muscle surgery was based on the degree of deviation in the primary position, and conventional recession and resection procedures were performed in 3 patients and hang-loose recession with an adjustable recession in 1. Single binocular vision was obtained in 3 patients in the primary position without prism correction or compensatory head posture. Electron-microscopic studies on the eye muscle specimens obtained at strabismus surgery revealed non-specific degenerative findings for the muscle fibers and sarcomeric disorganization compared to that in a control extraocular muscle.


Mosquito immunity against arboviruses.
Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector.


Significance of genome-wide analysis of copy number alterations and UPD in myelodysplastic syndromes using combined CGH - SNP arrays.
Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation, development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer. Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS. Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.


Improvement of durability of an organic photocatalyst in p-xylene oxygenation by addition of a Cu(II) complex.
The catalytic durability of an organic photocatalyst, 9-mesityl-10-methyl acridinium ion (Acr(+)-Mes), has been dramatically improved by the addition of [{tris(2-pyridylmethyl)amine}Cu(II)](ClO(4))(2) ([(tmpa)Cu(II)](2+)) in the photocatalytic oxygenation of p-xylene by molecular oxygen in acetonitrile. Such an improvement is not observed by the addition of Cu(ClO(4))(2) in the absence of organic ligands. The addition of [(tmpa)Cu](2+) in the reaction solution resulted in more than an 11 times higher turnover number (TON) compared with the TON obtained without [(tmpa)Cu(II)](2+). In the photocatalytic oxygenation, a stoichiometric amount of H(2)O(2) formation was observed in the absence of [(tmpa)Cu(II)](2+), however, much less H(2)O(2) formation was observed in the presence of [(tmpa)Cu(II)](2+). The photocatalytic mechanism was investigated by laser flash photolysis measurements in order to detect intermediates. The reaction of O(2)˙(-) with [(tmpa)Cu(II)](2+) monitored by UV-vis spectroscopy in propionitrile at 203 K suggested formation of [{(tmpa)Cu(II)}(2)O(2)](2+), a transformation which is crucial for the overall 4-electron reduction of molecular O(2) to water, and a key in the observed improvement in the catalytic durability of Acr(+)-Mes.


High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program.
Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.


Dilemmas in planning for the protection of children and youths in residential facilities.
Protection of children and youths after placement must be given increased emphasis because deinstitutionalized care is itself not harm-free and also because the needs of many children for care, control, and treatment are likely to be met in residential facilities for the foreseeable future. However, the diverse and often incompatible views of advocates and providers of child care about the issues affecting the protection of residents in institutions loom as obstacles to planning for the protection of children and youths after placement. Both of the extreme views of institutional abuse and neglect issues deny the need for child protection after placement. The first holds that since the child or youth is being protected and/or treated, no ongoing child protection is necessary. The other view holds that any child protection effort short of closing residential facilities is futile and therefore without merit. Underreporting of abuse or neglect is widespread; accountability of facilities for the protection of residents is, as a result, unevenly established. These conditions are attributable in part to the inadequate statutory base for protecting children in institutions. At the same time, because of the lack of a planned approach to protection within facilities, and between facilities and child protection agencies, residential facilities are likely to suffer negative public exposure when moderate or serious incidents of maltreatment become public. The absence of procedures for facilities themselves to recognize abuse and neglect invites exposure of incidents by staff and residents. The ad hoc manner in which incidents are managed by external agencies often inflicts unwarranted costs on the reputations of residential facilities that in many cases may have only one or two serious incidents a year. Finally, the use of "last resort" placements may be putting some children and youths into situations of unacceptable risk. Despite the existence of differing views in the residential care field, we have identified areas of agreement between the child protection agencies and residential facilities upon which public policy might build. The problem may not be so much that these attitudes exist, as that the states have not responded in a planned and credible way to the problem of institutional abuse and neglect. Nevertheless, development of a planned and credible approach must deal with these areas of difference if protection of children after placement is to be improved.


[The functions of stress proteins in recent research].
Stress proteins are highly conserved among all living organisms and play important roles in protection of cells against environmental stresses. At the same time, stress proteins function also in cells under normal conditions as molecular chaperones in assisting cellular proteins in folding and assembly.


The Systemic Inflammation-Based Prognostic Score Predicts Postoperative Complications in Patients Undergoing Pancreaticoduodenectomy.
Although many studies have confirmed the correlation between inflammation-based or nutritional markers and postoperative complications in patients undergoing colorectal cancer surgery, their correlation after undergoing pancreaticoduodenectomy (PD) remains unclear. We retrospectively reviewed the clinical data of patients who underwent PD in Beijing Friendship hospital between 2018 and 2020. Univariate analysis, multivariate analysis, and receiver operating characteristic curve (ROC) were performed. We assessed the preoperative modified Glasgow Prognostic Score (mGPS), C-reactive protein/albumin ratio (CAR), C-reactive protein (CRP), postoperative Glasgow Prognostic Score (poGPS), CRP on postoperative day 3 (POD3) and CAR on POD3. The optimal cut-off values were determined by performing logistic regression analysis. Of the 172 patients who underwent PD, 74 (43.0%) developed complications, of whom 27 (15.7%) had clinically relevant postoperative pancreatic fistulas (CR-POPF) and 36 (20.9%) had positive drainage fluid cultures. Elevated levels of preoperative mGPS (P<0.001), poGPS (P<0.001), CRP (P<0.001) and CAR on POD3 were associated with postoperative complications. CRP on POD3 (OR=1.028, 95% CI=1.017-1.039, P<0.001) was an independent risk factor associated with postoperative complications in both univariate and multivariate analyses. CAR on POD 3 showed the largest area under the curve (AUC=0.883, P<0.001). Compared with CAR<4.86, CAR ≥4.86 on POD3 was associated with a higher probability of complications (85.5% vs 14.6%, P<0.001), especially CR-POPF (33.3% vs 4.9%, P<0.001), intra-abdominal infection (36.2% vs 10.7%, P<0.001) with a positive drainage fluid culture. CAR, an inflammatory response-based marker, can effectively predict early postoperative complications in patients undergone PD.