Company, country, connections: counterfactual origins increase organizational commitment, patriotism, and social investment.
Four studies examined the relationship between counterfactual origins--thoughts about how the beginning of organizations, countries, and social connections might have turned out differently--and increased feelings of commitment to those institutions and connections. Study 1 found that counterfactually reflecting on the origins of one's country increases patriotism. Study 2 extended this finding to organizational commitment and examined the mediating role of poignancy. Study 3 found that counterfactual reflection boosts organizational commitment even beyond the effects of other commitment-enhancing appeals and that perceptions of fate mediate the positive effect of counterfactual origins on commitment. Finally, Study 4 temporally separated the counterfactual manipulation from a behavioral measure of commitment and found that counterfactual reflection predicted whether participants e-mailed social contacts 2 weeks later. The robust relationship between counterfactual origins and commitment was found across a wide range of companies and countries, with undergraduates and M.B.A. students, and for attitudes and behaviors.


Psychoactive pollution suppresses individual differences in fish behaviour.
Environmental contamination by pharmaceuticals is global, substantially altering crucial behaviours in animals and impacting on their reproduction and survival. A key question is whether the consequences of these pollutants extend beyond mean behavioural changes, restraining differences in behaviour between individuals. In a controlled, two-year, multigenerational experiment with independent mesocosm populations, we exposed guppies (Poecilia reticulata) to environmentally realistic levels of the ubiquitous pollutant fluoxetine (Prozac). Fish (unexposed: n = 59, low fluoxetine: n = 57, high fluoxetine: n = 58) were repeatedly assayed on four separate occasions for activity and risk-taking behaviour. Fluoxetine homogenized individuals' activity, with individual variation in populations exposed to even low concentrations falling to less than half that in unexposed populations. To understand the proximate mechanism underlying these changes, we tested the relative contribution of variation within and between individuals to the overall decline in individual variation. We found strong evidence that fluoxetine erodes variation in activity between but not within individuals, revealing the hidden consequences of a ubiquitous contaminant on phenotypic variation in fish-likely to impair adaptive potential to environmental change.


Enantioseparation of nornicotine in tobacco by ultraperformance convergence chromatography with tandem mass spectrometry.
Nornicotine, an alkaloid constituent of tobacco, is a precursor to the carcinogen N-nitrosonornicotine that is produced during the curing and processing of tobacco. Accumulating evidence reveals that nornicotine enantiomers have different neurochemical and behavioral effects. In the present study, an accurate and rapid method was developed for the enantioseparation of (R)-(+)-nornicotine and (S)-(-)-nornicotine enantiomers in tobacco by ultra-performance convergence chromatography with tandem mass spectrometry. Chromatographic conditions were investigated to achieve the optimal resolution of two enantiomers. Results indicated that (R)-(+)-nornicotine and (S)-(-)-nornicotine could be separated within 5 min when ammonium hydroxide was added into the cosolvent, and the best resolution (Rs = 4.76) was achieved on a immobilized cellulose tris-(3,5-dichlorophenylcarbamate) chiral stationary phase. The proposed method was validated and was finally applied to analyze the compositions of (R)-(+)-nornicotine and (S)-(-)-nornicotine in three typical types of tobaccos (flue-cured, burley, and oriental). It was found that, enantiomer fraction of nornicotine (the proportion of (S)-(-)-nornicotine in the nornicotine pool) in burley tobacco samples was relatively high and constant compared with flue-cured and oriental tobaccos. The effective and rapid enantioseparation of nornicotine may help the understanding of alkaloid metabolites in different tobacco varieties and may also benefit pharmacological studies of alkaloid enantiomers.


Elaidic acid (EA) generates dysfunctional high-density lipoproteins and consumption of EA exacerbates hyperlipidemia and fatty liver change in zebrafish.
It is well known that trans-fatty acids have proatherogenic properties while HDL has antiatherogenic activities in plasma. However, there has been no report on the effects of trans-fat on the functional and structural properties of HDL. To compare physiological properties, we synthesized reconstituted HDL (rHDL) containing stearic acid (18:0), oleic acid (18:1, cis), or elaidic acid (EA, 18:1, trans). An rHDL containing EA (EA-rHDL) showed loss of antioxidant ability and induced the highest uptake of oxidized LDL into human macrophages. EA-rHDL caused the strongest cellular senescence in human dermal fibroblast cells along with the highest production of inflammatory species in macrophages co-treated with fructose. Injection of EA-rHDL into zebrafish embryos resulted in acute embryonic toxicity with the lowest survivability. Consumption of trans-fat for 20 weeks resulted in remarkable hyperlipidemia, elevation of serum cholesteryl ester transfer protein activity, hepatic inflammation, and fatty liver changes. Incorporation of EA impaired the beneficial effects of rHDL against atherogenesis. In zebrafish, EA-rHDL resulted in acute embryonic toxicity, and consumption of EA caused remarkable hyperlipidemia, inflammation, and fatty liver changes.


Intrinsic laryngeal muscle reinnervation using the muscle-nerve-muscle technique.
This study was performed to investigate the muscle-nerve-muscle reinnervation technique in the larynx, in which a nerve conduit implanted into an innervated muscle conducts axonal sprouting into a denervated muscle while maintaining function of the donor muscle. In this study, the muscle-nerve-muscle technique was used to direct superior laryngeal nerve axons to reinnervate intrinsic laryngeal muscles by implanting the recurrent laryngeal nerve stump into the cricothyroid muscle in 8 dogs. In 4 of the dogs, the recurrent laryngeal nerve trunk to the adductor muscles was divided so that all axonal sprouting was directed to the posterior cricoarytenoid muscle. Six-month electromyography data were obtained from 6 of the 8 dogs. All 6 dogs showed evidence of successful reinnervation of the thyroarytenoid or posterior cricoarytenoid muscles with action potentials that corresponded to spontaneous respiratory efforts, while the donor cricothyroid muscles retained their phasic contraction. These responses were obliterated when the recurrent laryngeal nerve conduit was divided. Histologic examination of the intrinsic laryngeal muscles demonstrated successful reinnervation. The results confirm that intrinsic laryngeal muscles may be successfully reinnervated by the superior laryngeal nerve with the muscle-nerve-muscle technique, without sacrifice of function of the cricothyroid muscle. This method offers an alternative source of appropriately firing axons for laryngeal reinnervation procedures.


[Toxicological and hygienic evaluation of water obtained by the method of hydration of carbon dioxide].
The irritating, sensitizing, and toxic effect of water produced by the method of carbon dioxide hydration was examined in animal experiments and human observations. It was found that before and after decontamination this water did not cause skin irritation or organism sensitization, did not have a toxic effect on the CNS, liver, kidneys or blood morphology, and did not deteriorate adaptive capabilities of the animal or human body.


Multi-scale and angular analysis of ray-optical light trapping schemes in thin-film solar cells: micro lens array, V-shaped configuration, and double parabolic trapper.
An efficient light trapping scheme is a key to enhancing the power conversion efficiency (PCE) of thin-film photovoltaic (PV) cells by compensating for the insufficient light absorption. To handle optical components from nano-scale to micro-scale seamlessly, a multi-scale optical simulation is carefully designed in this study and is used to qualitatively analyze the light trapping performances of a micro lens array (MLA), a V-shaped configuration, and the newly proposed scheme, which is termed a double parabolic trapper (DPT) according to both daily and annual movement of the sun. DPT has the potential to enhance the PCE significantly, from 5.9% to 8.9%, for PCDTBT:PC(70)BM-based polymer solar cells by perfectly trapping the incident light between two parabolic PV cells.


Sonographic Features of Palpable Breast and Axillary Lesions in Adult Male Patients: A Pictorial Essay.
The male breast is a non-functional and rudimentary organ, but similarly to the female breast, it can be affected by various diseases. In contrast to female breast cancer, male breast cancer has a low incidence, and there is no established breast cancer screening program for male patients. Therefore, the diagnostic evaluation is usually performed in male patients with symptoms such as palpability or pain in the breasts. Furthermore, most adult male patients who visit breast clinics sometimes present with not only breast symptoms but also axillary symptoms, and both the breast and axilla are usually examined during breast ultrasonography in daily clinical practice. The purpose of this pictorial essay was to present the sonographic features of various palpable breast and axillary lesions in adult male patients.


A Case Report on Apocrine Encapsulated Papillary Carcinoma of the Breast with Frank Invasion: A Diagnostic Quandary.
Encapsulated papillary carcinoma is a special type of breast cancer defined in the fifth edition of the World Health Organization breast tumor classification guidelines. Apocrine encapsulated papillary carcinoma is extremely rare, and only 10 cases have been described previously. We encountered a case of apocrine encapsulated papillary carcinoma with frank invasion. The patient was a 77-year-old woman with a painless mass in her right breast. Core needle biopsy revealed that the tumor cells had voluminous eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. We diagnosed this lesion as carcinoma with apocrine differentiation and suggested the possibility of an encapsulated papillary carcinoma. The patient underwent a right-sided mastectomy. Gross examination of the resected specimen revealed a multilobulated tumor. Microscopically, the tumor cells, which had voluminous eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli, proliferated in papillary fashion with fibrous stalks in the cystic space. Myoepithelial cells were not observed around the cystic space. Frank invasion was also observed around the encapsulated papillary carcinoma. Immunohistochemistry analysis revealed that the tumor cells were negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and positive for androgen receptor and gross cys-tic disease fluid protein 15. Based on these findings, we diagnosed this lesion as an apocrine encapsulated papillary carcinoma with frank invasion.


[Isolation and properties of chymotrypsin and trypsin labeled with iodine radioisotopes].
Comparative study of iodination of chymotrypsin and trypsin was carried out using either iodine monochloride or the electrochemical procedure under conditions of controlled anode potential. It was shown that a part of iodine monochloride was consumed for oxidation of protein molecules. As a result of this process specific activity of the enzymes was decreased down to 50-60% of the initial activity after introduction of 2 atoms of iodine per a molecule. The similar degree of iodination under mild conditions of electrolysis in potentiostatic experiments caused considerably lower decrease in the enzymatic activity, reaching 5-10% of the initial activity (after introduction of I atom of iodine per a molecule--2.5%); labelling of trypsin and chymotrypsin by means of iodine radionuclides is promising for various medico-biological purposes.


Multiple proteolytic action of rat liver cathepsin B: specificities and pH-dependences of the endo- and exopeptidase activities.
Dipeptidylcarboxypeptidase, endopeptidase, and carboxypeptidase activities of rat liver cathepsin B were investigated using soluble denatured protein substrates, reduced and S-(3-trimethylammonio)propylated proteins and their derivatives. It was found that the soluble denatured proteins were degraded mainly by the dipeptidylcarboxypeptidase activity and in a few cases by the endopeptidase and carboxypeptidase activities. The eipeptidylcarboxypeptidase activity showed broad substrate specificity with broad pH optimum at 4-6. A peptide having the alpha-carboxyl group amidated with methylamine could also be a good substrate for this activity. These results suggest that this activity is dependent not upon the dissociated alpha-carboxyl group at the P2' site but upon the hydrogen-bonding abilities of the alpha-imino moiety and the protonated or amidated alpha-carboxyl moiety at P2'. On the other hand, the endopeptidase and carboxypeptidase activities were observed in a few cases, suggesting that special amino acid sequences in the substrates are responsible for these activities. These activities showed sharp pH optima at 6 and seemed to prefer basic amino acid residues at P1 site. Therefore, we suppose that cathepsin B has a carboxyl group with a pKa of about 5.5 at the S1 subsite which more effectively interacts with a positive charge at the P1 site of the substrate at pH 6 than at pH 5. Based on these results, a model of the binding subsites of this enzyme is proposed.


Prevention of overweight and obesity: how effective is the current public health approach.
Obesity is a public health problem that has become epidemic worldwide. Substantial literature has emerged to show that overweight and obesity are major causes of co-morbidities, including type II diabetes, cardiovascular diseases, various cancers and other health problems, which can lead to further morbidity and mortality. The related health care costs are also substantial. Therefore, a public health approach to develop population-based strategies for the prevention of excess weight gain is of great importance. However, public health intervention programs have had limited success in tackling the rising prevalence of obesity. This paper reviews the definition of overweight and obesity and the variations with age and ethnicity; health consequences and factors contributing to the development of obesity; and critically reviews the effectiveness of current public health strategies for risk factor reduction and obesity prevention.


Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease.
We studied the course of virologic breakthroughs detected by a quantitative polymerase chain reaction (PCR) assay in 32 of 78 patients with hepatitis B e antigen (HBeAg)-negative precore mutant hepatitis B virus (HBV) chronic liver disease under long-term lamivudine monotherapy. Serum HBV DNA levels were measured every 3 months and on every biochemical breakthrough. YMDD mutants were detected in 30 of the 32 patients with virologic breakthroughs. Among these 32 patients, biochemical remission rate was 44% at 6 months, 21% at 12 months, and 0% at 24 months after the onset of virologic breakthrough. Development of biochemical breakthroughs was associated with a significant increase of serum HBV DNA levels, which exceeded 100,000 copies/mL in 19 of 20 patients (95%) with biochemical breakthroughs and in only 1 of 8 patients (12.5%) remaining in biochemical remission for at least 6 months after the onset of virologic breakthrough (P <.001). Alanine aminotransferase (ALT) level peaked within 0 to 3 months after the onset of biochemical breakthrough and decreased at 6 months but remained abnormal in all but 2 patients. Follow-up liver histologic lesions in patients with biochemical breakthroughs did not differ from baseline findings, although they were significantly improved in patients remaining in virologic and biochemical remission. In conclusion, the frequent emergence of viral resistance under long-term lamivudine monotherapy in HBeAg-negative precore mutant HBV chronic liver disease is followed by increasing viremia levels culminating in the development of biochemical breakthroughs in most cases. ALT activity peaks close to the onset of biochemical breakthrough, decreasing thereafter but remaining persistently abnormal with fluctuating levels.


The Vanderbilt University neurosurgical heritage.
The Vanderbilt University Hospital heritage was influenced by the excellence of the Johns Hopkins era--by Osler, Halsted, Cushing, Brooks, and many others. Upon this strong origin, the neurosurgery department was built by Cobb Pilcher and perpetuated by William F. Meacham.


Structural basis for xyloglucan specificity and α-d-Xylp(1 → 6)-D-Glcp recognition at the -1 subsite within the GH5 family.
GH5 is one of the largest glycoside hydrolase families, comprising at least 20 distinct activities within a common structural scaffold. However, the molecular basis for the functional differentiation among GH5 members is still not fully understood, principally for xyloglucan specificity. In this work, we elucidated the crystal structures of two novel GH5 xyloglucanases (XEGs) retrieved from a rumen microflora metagenomic library, in the native state and in complex with xyloglucan-derived oligosaccharides. These results provided insights into the structural determinants that differentiate GH5 XEGs from parental cellulases and a new mode of action within the GH5 family related to structural adaptations in the -1 subsite. The oligosaccharide found in the XEG5A complex, permitted the mapping, for the first time, of the positive subsites of a GH5 XEG, revealing the importance of the pocket-like topology of the +1 subsite in conferring the ability of some GH5 enzymes to attack xyloglucan. Complementarily, the XEG5B complex covered the negative subsites, completing the subsite mapping of GH5 XEGs at high resolution. Interestingly, XEG5B is, to date, the only GH5 member able to cleave XXXG into XX and XG, and in the light of these results, we propose that a modification in the -1 subsite enables the accommodation of a xylosyl side chain at this position. The stereochemical compatibility of the -1 subsite with a xylosyl moiety was also reported for other structurally nonrelated XEGs belonging to the GH74 family, indicating it to be an essential attribute for this mode of action.


Clinical Impact of Piecemeal Resection Concerning the Lateral Spread of Ampullary Adenomas.
Objective Endoscopic papillectomy (EP) has been recognized to be a safe and reliable treatment modality for ampullary adenomas. The purpose of this study was to determine the safety and efficacy of endoscopic piecemeal resection for laterally spreading ampullary adenomas and to compare these findings with a control population of smaller conventional ampullary tumors treated in the same time period. Methods Between May 1999 and September 2015, 136 patients underwent EP at Tokyo Medical University hospital. A total of 125 patients underwent en bloc resection, and 11 patients underwent piecemeal resection. Results The final pathological diagnoses were 103 adenomas, 14 carcinomas in adenomas, 4 carcinomas, and 4 hyperplasia in the en bloc resection group, versus 7 adenomas, 3 carcinomas in adenoma, and 1 carcinomas in the piecemeal resection group. A single treatment session was possible in 104 (83.2%) of the 125 patients in the en bloc resection group and in 8 (72.7%) of the 11 in the piecemeal resection group. The total resection rate including additional treatments was 98.4% in the en bloc resection group and 100% in the piecemeal resection group. Conclusion Piecemeal resection for laterally spreading ampullary adenomas was sufficiently performed compared with en bloc resection.


DNA damage induction by two halogenated acetaldehydes, byproducts of water disinfection.
Drinking water contains disinfection byproducts, generated by the interaction of chlorine (or other disinfecting chemicals) with organic matter, anthropogenic contaminants, and bromide/iodide naturally present in most source waters. One class of these chemicals is the halogenated acetaldehydes (HAs), identified in high quantities when ozone is used as primary or secondary disinfectant. In this study, an analysis of the genotoxic potential of two HAs, namely tribromoacetaldehyde (TBA) and chloral hydrate (CH) has been conducted in human cells (TK6 cultured cells and peripheral blood lymphocytes). The comet assay was used to 1) measure the induction of single and double-strand DNA breaks, 2) evaluate the capacity of inducing oxidative DNA damage, and 3) determine the DNA repair kinetics of the induced primary genetic damage. In addition, chromosome damage, as a measure of fixed damage, was evaluated by means of the micronucleus test. The results of the comet assay show that both compounds are clearly genotoxic, inducing high levels of DNA breaks, TBA being more effective than CH. According to the comet results, both HAs produce high levels of oxidized bases, and the induced DNA damage is rapidly repaired over time. Contrarily, the results obtained in the micronucleus test, which measures the capacity of genotoxic agents to induce clastogenic and aneugenic effects, are negative for the two HAs tested, either using TK6 cells or human peripheral blood lymphocytes. This would indicate that the primary damage induced by the two HAs is not fixed as chromosome damage, possibly due to an efficient repair or the death of damaged cells, which is an important point in terms of risk assessment of DBPs exposure.


First-ever ischemic stroke and increased risk of incident heart disease in older adults.
Poststroke cardiac complications are common. It is unknown whether the reason is shared risk factors and preexisting heart disease or stroke-associated myocardial and coronary injury. We tested the hypothesis that first-ever ischemic stroke is associated with increased risk of incident cardiovascular complications in patients without known preexisting cardiac comorbid conditions. This population-based cohort study included residents in Ontario between 2002 and 2012 who were ≥66 years of age without known cardiovascular disease. We compared the incident risk of major adverse cardiovascular events (MACE), defined as myocardial infarction, unstable angina, congestive heart failure, coronary artery disease, coronary artery revascularization, or cardiovascular death, at 1 year in patients with first-ever ischemic stroke vs propensity-matched individuals without stroke (4:1 matching using 31 variables). To estimate cause-specific hazard ratios (HRs), we used Cox regression models adjusted for variables with weighted standardized differences >0.10 or known to influence the risk of MACE. We included 21,931 patients with first-ever ischemic stroke and 71,696 propensity-matched individuals, well balanced on all variables used for propensity matching. First-ever ischemic stroke was associated with increased unadjusted incident MACE risk (HR 4.5, 95% confidence interval [CI] 4.3-4.8). MACE adjusted risk was highest in the first 30 days (HR 25.0, 95% CI 20.5-30.5) and declined both at 31 to 90 days (HR 4.8, 95% CI 4.1-5.7) and at 91 to 365 days (HR 2.2, 95% CI 2.0-2.4). In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE. Whether this association is explained by stroke-associated cardiac injury, preexisting subclinical cardiovascular comorbid conditions, or both remains unknown.


Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes.
Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was likely to be developed as a therapeutic agent for this disease.


Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity.
Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza-Rev and cryopreserved. Subsequent stem cell mobilization was followed by high-dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.


A within farm clinical trial to compare two treatments (parenteral antibacterials and hoof trimming) for sheep lame with footrot.
From observational studies, farmers who use parenteral antibacterials to promptly treat all sheep with footrot (FR) or interdigital dermatitis (ID) have a prevalence of lameness of < 2% compared with a prevalence of 9% lameness reported by farmers who treat lame sheep by trimming affected feet. We tested the hypothesis that prompt treatment of sheep lame with naturally developing FR or ID with parenteral and topical antibacterials reduces the prevalence and incidence of lameness with these conditions compared with less frequent treatment with trimming of hoof horn and applying topical antibacterials.A further hypothesis was that reduction of ID and FR would improve productivity. A lowland sheep flock with 700 ewes was used to test these hypotheses in an 18-month within farm clinical trial with four groups of ewes: two intervention and two control. The duration and severity of lameness was used to categorise sheep into three weighted scores of lameness (WLS): never lame (WLS0), mildly lame/lame for < 6 days (WLS1) and severely or chronically lame (WLS2). The intervention reduced the prevalence of lameness due to FR and ID in ewes and lambs and the incidence of lameness in ewes. The WLS was also significantly lower in sheep in the intervention groups. Ewes with a higher WLS were subsequently significantly more likely to have a body condition score < 2.5 and to have lame lambs. Significantly more ewes lambed and successfully reared more lambs that were ready for slaughter at a younger age in the intervention versus control groups. There was an increase in the gross margin of Pound630/100 ewes mated in the intervention group, including the cost of treatment of Pound150/100 ewes mated. We conclude that prompt parenteral and topical antibacterial treatment of sheep lame with ID and FR reduced the prevalence and incidence of these infectious conditions and led to improved health, welfare and productivity.


Early mobilization in the intensive care unit: a systematic review.
The purpose of this review is to evaluate the literature related to mobilization of the critically ill patient with an emphasis on functional outcomes and patient safety. We searched the electronic databases of PubMed, CINAHL, Medline (Ovid), and The Cochrane Library for a period spanning 2000-2011. Articles used in this review included randomized and nonrandomized clinical trials, prospective and retrospective analyses, and case series in peer-reviewed journals. Sackett's Levels of Evidence were used to classify the current literature to evaluate the strength of the outcomes reported. Fifteen studies met inclusion criteria and were reviewed. According to Sackett's Levels of Evidence, 9 studies were level 4 evidence, one study was level 3, 4 studies were level 2, and one study was level one evidence. Ten studies pertained to patient safety/feasibility and 10 studies pertained to functional outcomes with 5 fitting into both categories. A search of the scientific literature revealed a limited number of studies that examined the mobilization of critically ill patients in the intensive care unit. However, literature that does exist supports early mobilization and physical therapy as a safe and effective intervention that can have a significant impact on functional outcomes.


[Ultrastructure of hepatocytes after local cooling of the liver].
Electron-microscopic and stereometric study of hepatocyte ultrastructure with local liver cooling to -30 degrees C have been performed using the method of vital fixation by rat liver perfusion. Quantitative and qualitative data obtained testify to the presence of destructive changes in hepatocytes immediately after thawing expressed in hyaloplasm lightening, formation of cavities in cytoplasm and injury of mitochondria membrane and endoplasmic reticulum integrity. Changes in nuclear structure of hepatocytes and Kupffer cells (widening of nuclear pores and channels in condensed chromatine, as well as the presence of ribosomal complexes in the nucleus and edge position of the nucleolus) may be connected with the beginning of the reparation process.


Evidence for cytoplasmic P-glycoprotein location associated with increased multidrug resistance and resistance to chemosensitizers.
A new human myeloma cell line, 8226/MDR10V, was selected from a P-glycoprotein-positive cell line, 8226/Dox40, in the continuous presence of doxorubicin and verapamil. MDR10V cells are 13-fold more resistant to doxorubicin and 4-fold more resistant to vincristine than the parent cell line, Dox40. Chemosensitizers are also less effective in reversing resistance in the MDR10V compared to the Dox40 cells. Despite higher resistance to cytotoxic agents, MDR10V expresses 40% less P-glycoprotein in the plasma membrane compared to Dox40; however, total cellular P-glycoprotein is the same in both cell lines. Confocal immunofluorescence microscopy shows 2.5-fold more P-glycoprotein in the cytoplasm of MDR10V cells as compared to Dox40 cells. The cytoplasmic location of P-glycoprotein in the MDR10V cells is associated with a redistribution of doxorubicin. In Dox40 cells, doxorubicin is concentrated in the nucleus, whereas in MDR10V cells, 90% of doxorubicin is found in the cytoplasm. In the presence of equivalent intracellular doxorubicin, there was a decrease in DNA-protein crosslinks in the MDR10V cell line compared to the Dox40 cell line. This finding is in agreement with the intracellular doxorubicin fluorescence studies showing less doxorubicin in the nuclei of MDR10V cells compared to Dox40 cells. Verapamil is less effective in increasing doxorubicin accumulation in the nuclei of MDR10V cells compared to Dox40 cells. Processing of P-glycoprotein from the endoplasmic reticulum to the medial Golgi was identical between the two cell lines as determined by endoglycosidase H sensitivity of newly sensitized P-glycoprotein. No mutations were found in MDR1 cDNA from MDR10V cells compared to Dox40 cells. These results suggest that resistance to chemosensitizing agents plus cytotoxic drugs is associated with a redistribution of P-glycoprotein from the plasma membrane to the cytoplasm, which in turn reduces the amount of cytotoxic drug reaching the nucleus.


Extent of formation of O4-methylthymidine in calf thymus DNA methylated by N-methyl-N-nitrosourea and lack of repair of this product by rat liver O6-alkylguanine-DNA-alkyltransferase.
Calf thymus DNA was methylated by reaction with N-[3H]-methyl-N-nitrosourea and the content of O6-methyldeoxyguanosine, 3-methylthymidine and O4-methylthymidine was determined. It was found that O4-methylthymidine represented only 0.06 +/- 0.02% of the total methylation and that the ratio of O6-methyldeoxyguanosine:O4-methylthymidine was 126 +/- 31. 3-Methylthymidine represented only 0.05 +/- 0.01% of the total radioactivity and the ratio of O6-methyldeoxyguanosine:3-methylthymidine was 171 +/- 16. The ability of O6-alkylguanine-DNA-alkyltransferases from Escherichia coli and from rat liver to repair O4-methylthymidine was determined using this methylated DNA as a substrate. When the methylated DNA substrate was incubated with an excess of either of the O6-alkylguanine-DNA-alkyltransferases greater than 95% of the O6-methyldeoxyguanosine was removed. The E. coli O6-alkylguanine-DNA-alkyltransferase also removed 89% of the O4-methylthymidine but the rat liver alkyltransferase did not alter the content of O4-methylthymidine. These results indicate that the mammalian O6-alkylguanine-DNA-alkyltransferase is specific for O6-methylguanine and differs from the bacterial protein in that it does not demethylate O4-methylthymine at any significant rate. This shows that the rat O6-alkylguanine-DNA-alkyltransferase is not able to protect against the possible hazards of the promutagenic lesion, O4-methylthymidine, but the very low extent of formation of this product may limit its significance in carcinogenesis and mutagenesis.


Sequencing topotecan and etoposide plus cisplatin to overcome topoisomerase I and II resistance: a pharmacodynamically based Phase I trial.
Resistance to topoisomerase (TOP) 1 and 2 inhibitors is a potentially important reason for treatment failure, and may be related, in part, to a down-regulation of the specific TOP target. Investigators in our laboratories previously noted such a down-regulation of the target, along with a reciprocal up-regulation of the alternate TOP. Therefore, sequencing TOP inhibitors may provide a means for overcoming resistance to the TOP I and II inhibitors. Furthermore, point mutations in TOP I, which confer resistance to TOP I inhibitors, were associated with collateral sensitivity to cisplatin. A dose escalating Phase I trial of topotecan (at doses of 0.75 to 1.0 mg/m(2)/day) on days 1 to 3 with etoposide (70-80 mg/m(2)/day) and cisplatin (20-25 mg/m(2)/day) on days 8 to 10. The timing of the drug sequence was based on the prior Phase I pharmacokinetic and pharmacodynamic studies of camptothecin and etoposide, and the level of the TOP targets in peripheral blood monocytes. Fifteen patients (7 males and 8 females) received 40 courses of therapy across three dose levels. The median age was 56 (range, 39-77), and the median performance status was 1 (range, 0-2). The diagnoses included: non-small cell lung cancer (7), head and neck cancer (2), cancer of unknown primary (2), and 1 each of ovarian cancer, prostate cancer, gastric cancer, and renal cancer. Level 1 (topotecan 1.0 mg/m(2)/day; etoposide 80 mg/m(2)/day; and cisplatin 25 mg/m(2)/day) produced severe and prolonged febrile neutropenia in the first patient treated, and the subsequent patients were then entered onto a reduced dose level (cohort 2: topotecan 0.75 mg/m(2)/day; etoposide 70 mg/m(2)/day; and cisplatin 20 mg/m(2)/day). Three of 6 patients on cohort 2 experienced grade IV neutropenia >5 days, and a decision was then made to add filgrastim at 5 micro g/kg rather than additionally reduce the dosages (cohort 3). Eight patients were then treated on cohort 3, and 1 of the 8 patients experienced a grade 4 neutropenia. Thus, cohort level three was considered the recommended dose for Phase II studies. Twelve of the 15 patients had disease assessable for response to therapy. Seven achieved stable disease for >/==" BORDER="0">2 months, whereas 5 showed continued progression of their disease. These data show that sequencing TOP 1 and 2 inhibitors is feasible, and topotecan 0.75 mg/m(2)/day days 1-3; etoposide 70 mg/m(2)/day days 8-10; and cisplatin 20 mg/m(2)/day days 8-10 with filgrastim at 5 micro g/kg is an appropriate dose and schedule to test the concept of modulating TOP levels by sequencing the administration of the respective TOP inhibitors.


Digital Holography as Computer Vision Position Sensor with an Extended Range of Working Distances.
Standard computer vision methods are usually based on powerful contact-less measurement approaches but applications, especially at the micro-scale, are restricted by finite depth-of-field and fixed working distance of imaging devices. Digital holography is a lensless, indirect imaging method recording the optical wave diffracted by the object onto the image sensor. The object is reconstructed numerically by propagating the recorded wavefront backward. The object distance becomes a computation parameter that can be chosen arbitrarily and adjusted to match the object position. No refractive lens is used and usual depth-of-field and working distance limitations are replaced by less restrictive ones tied to the laser-source coherence-length and to the size and resolution of the camera sensor. This paper applies digital holography to artificial visual in-plane position sensing with an extra-large range-to-resolution ratio. The object is made of a pseudoperiodic pattern allowing a subpixel resolution as well as a supra field-of-observation displacement range. We demonstrate an in-plane resolution of 50 nm and 0.002deg. in X, Y and θ respectively, over a working distance range of more than 15 cm. The allowed workspace extends over 12×10×150mm3. Digital holography extends the field of application of computer vision by allowing an extra-large range of working distances inaccessible to refractive imaging systems.


Defective regulation of IFNgamma and IL-12 by endogenous IL-10 in progressive MS.
MS is a chronic inflammatory disease of the CNS postulated to be a Th1 type cell-mediated autoimmune disease. There is increased interferon-gamma (IFNgamma) secretion in MS, and IFNgamma administration induces exacerbations of disease. IFNgamma expression is closely regulated by a number of cytokines produced by different cells of the immune system. Interleukin-12 (IL-12) is a major factor leading to Th1-type responses, including IFNgamma secretion, and there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both IL-12 and IFNgamma expression. The authors investigated cytokine production and proliferative responses of peripheral blood mononuclear cells stimulated with soluble anti-CD3 in healthy controls and patients with stable relapsing-remitting MS or progressive MS. The authors found that T cell receptor-mediated IFNgamma and IL-10 secretion were increased in progressive MS, whereas IL-4 and IL-2 secretion and lymphocyte proliferative responses were normal. Anti-IL-12 antibody suppressed raised IFNgamma in progressive MS but did not affect raised IL-10. In addition, neutralization of endogenous IL-10 upregulated IFNgamma in controls but not progressive MS. IL-10 was produced by CD4+ cells whereas IFNgamma was produced by both CD4+ and CD8+ cells. There were no differences in IL-10 receptor expression in MS patients. These abnormalities in IL-10 regulation were not seen in the relapsing-remitting form of MS. Thus, the defect in regulation of both IL-12 and IFNgamma production by endogenous IL-10 in progressive MS could be an important factor involved in the transition of MS from the relapsing to the progressive stage and has implications for treating MS patients with exogenous IL-10.


IV injection of air-filled human albumin microspheres to enhance arterial Doppler signal: a preliminary study in rabbits.
When air-filled human albumin microspheres are injected IV, they have been shown to traverse the pulmonary circulation and markedly influence the echogenicity of the left atrium and ventricle. We studied the possibility that the microspheres can be used to enhance the Doppler signal from systemic arteries and the portal vein. Doppler sonography of the aorta, renal artery, intrarenal branch, and portal vein was performed after the IV injection of saline or microspheres in doses of 1.0, 0.5, 0.3, and 0.1 ml in four rabbits. With appropriate blinding of the observers, subjective estimates of enhancement of the Doppler signal were made in each case. All injections of saline had no detectable effect. All four doses of microspheres enhanced the Doppler signal in the aorta in all rabbits. Signals from the renal artery enhanced in all rabbits after injections of 0.3 ml or greater, but in only two rabbits after 0.1 ml. Although the 1.0-ml dose enhanced the Doppler signal from the intrarenal arterial branch in all rabbits, the 0.5- and 0.3-ml doses enhanced signals in two and the 0.1-ml dose in one. The effect was typical for bolus IV injections. The mean time from injection to onset of enhancement was 5 sec and the effect lasted for 12 sec. Portal venous signals were evaluated in three rabbits. Ten injections were made, four at 1.0 ml and two at each of the lesser doses. Portal vein signals enhanced after all four injections of 1.0 ml of microspheres but after only one of the six injections of lower doses. Our results show that the IV injection of air-filled human albumin microspheres enhances the Doppler signal from systemic arteries and the portal vein and that the microspheres have the potential to serve as a contrast agent for Doppler sonography in humans.


Influence of Patient Goals of Care on Performance Measures in Patients Hospitalized for Heart Failure: An Analysis of the Enhanced Feedback For Effective Cardiac Treatment (EFFECT) Registry.
Pay for performance programs compare metrics that are risk-adjusted, but goals of care are not considered in current models. We conducted this study to explore the associations between do not resuscitate (DNR) designations, quality of care, and outcomes. Retrospective cohort study with chart review for inpatient quality metrics, 30 day mortality, and readmissions or death within 30 days of discharge in 96 Ontario hospitals participating in the Enhanced Feedback For Effective Cardiac Treatment (EFFECT) study in 2004/05. Of 8339 patients (mean age 77 years) with new heart failure, 1220 (15%) had DNR documented at admission (admission DNR, varying from 0% to 36% between hospitals) and 892 (11%) were switched from full resuscitation to DNR during their index hospitalization (later DNR). Death at 30 days was more common in patients with admission DNR (27%) or later DNR (35%) than full resuscitation (3%)-admission DNR was a stronger predictor (adjusted OR 8.6, 95% confidence interval 6.8-10.7) than any of the variables currently included in heart failure 30 day mortality risk models. Hospital-level rankings differed considerably if DNR patients were excluded: 22 of the 39 EFFECT hospitals in the top and bottom quintiles for 30 day mortality rates (the usual thresholds for rewards/penalties in current performance-based reimbursement schemes) would not have been in those same quintiles if admission DNR patients were excluded. Alternate goals of care are frequent and important confounders in heart failure comparative studies. Philosophy of care discussions should be considered for inclusion as a potential quality of care indicator.


The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope in iodide-accelerated spontaneous autoimmune thyroiditis.
Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.


Antiulcer activity of water soaked Glycine max L. grains in aspirin induced model of gastric ulcer in Wistar rats.
Glycine max L. with Drakshasava, widely used by traditional healers as a formulation for the treatment of peptic ulcer in rural northern Karnataka in India, appears to be effective as assessed by patients and in our previously published research work of traditionally used formulation. The present study was undertaken to evaluate the safety and efficacy of the overnight water soaked G. max grains. This is one of the components of traditional formulation. The study, approved by Institutional Animal Ethics Committee was carried out in male Wistar rats after assessing its toxicity in mice. Four groups of rats (n = 6 in each group) were treated with aspirin 200 mg/kg oral. In addition to aspirin control group received normal saline, standard group received 20 mg/kg omeprazole and 3(rd) and 4(th) group received G. max 250 and 500 mg/kg, respectively. All treatments were administered orally every 24 h for 7 days. After 24 hours fasting, on the 8(th) day stomach contents were aspirated under anesthesia to estimate free and total acidity. Stomachs were opened along the greater curvature to calculate ulcer index and subjected to histopathology studies. The results were analyzed by one-way analysis of variance followed-by Dunnett's post hoc test. P ≤0.05 was considered as significant. The severity of aspirin induced ulceration was found significantly (P < 0.05) decreased in test groups compared with the control group. Free and total acidity was significantly reduced in 500 mg/kg treated group, compared with the control group and was inferior to omeprazole treated group. The grain of G. max was found to be effective against aspirin induced ulcers.


Polynomial convolution algorithm for matrix multiplication with application for optical computing.
First, we describe an algorithm (the polynomial convolution algorithm) for the multiplication of two rectangular matrices A and B. The algorithm codes the matrix elements of A and B into two polynomials in a common indeterminate; the degree of the polynomial characterizing A depends on the size of both A and B, while the degree of the polynomial characterizing B only involves the size of B. The matrix elements of the product C = AB are obtainable from the convolution of the two polynomials. Although the resultant analysis is quite complex, its implementation in optical computing can be carried out in straightforward fashion (see Sec. III). The algorithm is at least as fast as the outer product and Kronecker product algorithms advocated by Athale- Collins and Barakat, respectively, in the assumed conditions of equally accessible matrix elements. Second, we consider the situation where the matrices are so large that they cannot be stored simultaneously on optical masks. It is shown that the speed advantages of the outer product and Kronecker product algorithms are now lost in this situation, whereas the polynomial convolution algorithm, because of its modular structure, is robust with respect to the storage problem. Finally, we consider some partitioning strategies in the light of the storage problem.


Early bone formation adjacent to oxidized and machined implant surfaces: a histologic study.
Various designs of dental implants representing different geometries and surface technologies are commercially available for patient treatment. However, data with regard to the biologic events that occur immediately after implant placement, regardless of the surface characteristic, are scarce. It has become a common procedure to perform immediate/early prosthetic loading rather than delayed loading. The goal of this study was to observe the early biologic events of peri-implant healing to understand the role of surface modifications in relation to the early phases of bone integration. The secondary goal was to observe the possible differences in the healing pattern at two oral implant surfaces differing in morphology and roughness (Ra, with Ra values ranging from 0.5 μm (machined surface; MS) to 1.5 μm (oxidized surface; OS). A total of 36 implants were placed in six foxhound dogs, equally divided between machined and oxidized surfaces. Three implants were positioned per hemimandible following a randomization scheme. Each animal was euthanized at a specific time point for histologic observation and histomorphometry: immediately after implant insertion and after 24 hours, 7 days, 15 days, 30 days, and 90 days. The study demonstrated an extremely low bone-implant contact (BIC) for both OS and MS implant surfaces during the first 15 days after implant placement (ranging from 12.9% to 26.9% independent of the implant surface). Increased BIC values were observed only in the 30- and 90-day specimens. The presence and the degradation of residual bone particles acted as centers for new bone formation, with osteoblasts lining osteoid tissue and subsequently woven bone independent of the implant surface characteristics. The bone-forming activity appeared strongly reduced after 30 days of healing and seemed to be complete only in the 90-day specimens, where abundant lamellar bone was evident. There is a continuing effort to develop improved titanium surfaces to achieve more rapid osseointegration and improve BIC, with the ultimate goal of applying occlusal load as early as possible. Since immediate or early implant loading is applied during and not after the first 15 days, the findings in the present study of an extremely low BIC and limited mineralized bone formation for both implant surfaces during the first 15 days after implant placement suggest that the surface roughness may not be a key factor for successful osseointegration of immediately or early loaded implants. Within the limits of this study, it can be stated that osseointegration follows a similar healing pattern with machined and oxidized implant surfaces.


Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis.
Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.


Limitations on diversity in basic science departments.
It has been over 30 years since the beginning of efforts to improve diversity in academia. We can identify four major stages: (1) early and continuing efforts to diversify the pipeline by increasing numbers of women and minorities getting advanced degrees, particularly in science, technology, engineering, and math (STEM); (2) requiring academic institutions to develop their own "affirmative action plans" for hiring and promotion; (3) introducing mentoring programs and coping strategies to help women and minorities deal with faculty practices from an earlier era; (4) asking academic institutions to rethink their practices and policies with an eye toward enabling more faculty diversity, a process known as institutional transformation. The thesis of this article is that research-intensive basic science departments of highly ranked U.S. medical schools are stuck at stage 3, resulting in a less diverse tenured and tenure-track faculty than seen in well-funded science departments of major universities. A review of Web-based records of research-intensive departments in universities with both medical school and nonmedical school departments indicates that the proportion of women and Black faculty in science departments of medical schools is lower than the proportion in similarly research-intensive university science departments. Expectations for faculty productivity in research-intensive medical school departments versus university-based departments may lead to these differences in faculty diversity.


Snapshot of a large dynamic replicon in a halophilic archaeon: megaplasmid or minichromosome?
Extremely halophilic archaea, which flourish in hypersaline environments, are known to contain a variety of large dynamic replicons. Previously, the analysis of one such replicon, pNRC100, in Halobacterium sp. strain NRC-1, showed that it undergoes high-frequency insertion sequence (IS) element-mediated insertions and deletions, as well as inversions via recombination between 39-kb-long inverted repeats (IRs). Now, the complete sequencing of pNRC100, a 191,346-bp circle, has shown the presence of 27 IS elements representing eight families. A total of 176 ORFs or likely genes of 850-bp average size were found, 39 of which were repeated within the large IRs. More than one-half of the ORFs are likely to represent novel genes that have no known homologs in the databases. Among ORFs with previously characterized homologs, three different copies of putative plasmid replication and four copies of partitioning genes were found, suggesting that pNRC100 evolved from IS element-mediated fusions of several smaller plasmids. Consistent with this idea, putative genes typically found on plasmids, including those encoding a restriction-modification system and arsenic resistance, as well as buoyant gas-filled vesicles and a two-component regulatory system, were found on pNRC100. However, additional putative genes not expected on an extrachromosomal element, such as those encoding an electron transport chain cytochrome d oxidase, DNA nucleotide synthesis enzymes thioredoxin and thioredoxin reductase, and eukaryotic-like TATA-binding protein transcription factors and a chromosomal replication initiator protein were also found. A multi-step IS element-mediated process is proposed to account for the acquisition of these chromosomal genes. The finding of essential genes on pNRC100 and its property of resistance to curing suggest that this replicon may be evolving into a new chromosome.


Clinical and Pathological Findings on Intoxication by Yellow Phosphorus After Ingesting Firework Cracker: A Rare Case of Autopsy.
Yellow phosphorus is a toxic substance used in the production of firework cracker, fireworks, ammunition and agricultural dung. When ingested, it shows its effects mainly in the liver, the kidneys, and the brain. A four-year-old girl had died as a result of acute hepatic failure caused by ingesting a firework cracker. The case showed high levels of hepatic enzymes, along with non-specific signs such as nausea, vomiting and diarrhea. Autopsy revealed diffuse microvesicular steatosis in the liver and disseminated degeneration in the proximal tubules of the kidneys. In cases with concomitant hepatorenal failure and cardiovascular collapse, death is inevitable. However, when only hepatic failure develops, hepatic transplantation may be lifesaving. Although intoxication from ingesting yellow phosphorus has a very high rate of mortality, forensic cases are extremely rare in the literature.


Nature-Derived Polysaccharide-Based Composite Hydrogels for Promoting Wound Healing.
Numerous innovative advancements in dressing technology for wound healing have emerged. Among the various types of wound dressings available, hydrogel dressings, structured with a three-dimensional network and composed of predominantly hydrophilic components, are widely used for wound care due to their remarkable capacity to absorb abundant wound exudate, maintain a moisture environment, provide soothing and cooling effects, and mimic the extracellular matrix. Composite hydrogel dressings, one of the evolved dressings, address the limitations of traditional hydrogel dressings by incorporating additional components, including particles, fibers, fabrics, or foams, within the hydrogels, effectively promoting wound treatment and healing. The added elements enhance the features or add specific functionalities of the dressings, such as sensitivity to external factors, adhesiveness, mechanical strength, control over the release of therapeutic agents, antioxidant and antimicrobial properties, and tissue regeneration behavior. They can be categorized as natural or synthetic based on the origin of the main components of the hydrogel network. This review focuses on recent research on developing natural polysaccharide-based composite hydrogel wound dressings. It explores their preparation and composition, the reinforcement materials integrated into hydrogels, and therapeutic agents. Furthermore, it discusses their features and the specific types of wounds where applied.


A distal modular enhancer complex acts to control pituitary- and nervous system-specific expression of the LHX3 regulatory gene.
Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency.


Restriction endonuclease analysis of Marek's disease virus DNA and homology between strains.
The restriction endonuclease patterns of viral DNA obtained from serotypes 1 and 2 strains of Marek's disease virus have been compared and homology between the strains examined by hybridization. The results have shown that HPRS 16 (serotype 1) DNA has a structure similar to its attenuated variant HPRS 16/att except for a few fragments that are present only in the virulent strain. Evidence was obtained which suggested that these restriction fragments contained repeat sequences and that insertion of heterogeneous DNA occurred at these sites during attenuation of HPRS 16. The restriction enzyme patterns of HPRS 24 (serotype 2) differed substantially from those of HPRS 16 and HPRS 16/att and reassociation experiments showed that HPRS 24 shares less than 10% homology with either HPRS 16 or herpesvirus of turkeys (serotype 3).


Resurgence of Malaria Following Discontinuation of Indoor Residual Spraying of Insecticide in an Area of Uganda With Previously High-Transmission Intensity.
Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the primary tools for malaria prevention in Africa. It is not known whether reductions in malaria can be sustained after IRS is discontinued. Our aim in this study was to assess changes in malaria morbidity in an area of Uganda with historically high transmission where IRS was discontinued after a 4-year period followed by universal LLIN distribution. Individual-level malaria surveillance data were collected from 1 outpatient department and 1 inpatient setting in Apac District, Uganda, from July 2009 through November 2015. Rounds of IRS were delivered approximately every 6 months from February 2010 through May 2014 followed by universal LLIN distribution in June 2014. Temporal changes in the malaria test positivity rate (TPR) were estimated during and after IRS using interrupted time series analyses, controlling for age, rainfall, and autocorrelation. Data include 65 421 outpatient visits and 13 955 pediatric inpatient admissions for which a diagnostic test for malaria was performed. In outpatients aged <5 years, baseline TPR was 60%-80% followed by a rapid and then sustained decrease to 15%-30%. During the 4-18 months following discontinuation of IRS, absolute TPR values increased by an average of 3.29% per month (95% confidence interval, 2.01%-4.57%), returning to baseline levels. Similar trends were seen in outpatients aged ≥5 years and pediatric admissions. Discontinuation of IRS in an area with historically high transmission intensity was associated with a rapid increase in malaria morbidity to pre-IRS levels.


Lifestyle risk score and mortality in Korean adults: a population-based cohort study.
Individual lifestyle risk factors have been associated with an increased risk of mortality. However, limited evidence is available on the combined association of lifestyle risk factors with mortality in non-Western populations. The analysis included 37,472 participants (aged ≥19 years) in the Korea National Health and Nutrition Examination Surveys (2007-2014) for whom the data were linked to death certificates/medical records through December 2016. A lifestyle risk score was created using five unhealthy behaviors: current smoking, high-risk alcohol drinking, unhealthy weight, physical inactivity, and insufficient/prolonged sleep. Cox proportional hazards models were used to estimate hazard ratio (HR) and 95% confidence interval (CI). During up to 9 years of follow-up, we documented 1,057 total deaths. Compared to individuals with zero lifestyle risk factor, those with 4-5 lifestyle risk factors had 2.01 times (HR = 2.01, 95% CI = 1.43-2.82) and 2.59 times (HR = 2.59, 95% CI = 1.24-5.40) higher risk of all-cause and cardiovascular mortality, respectively. However, higher lifestyle risk score was not significantly associated with cancer mortality (p-trend >0.05). In stratified analyses, the positive associations tended to be stronger in adults aged <65 years, unemployed, and those with lower levels of education. In conclusion, combined unhealthy lifestyle behaviors were associated with substantially increased risk of total and cardiovascular mortality in Korean adults.


Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis.
Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis. Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected. Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage. Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis.


[Role of risk factors in the development of chronic digestive system diseases in children].
The spread, patterns, and risk factors of alimentary diseases were examined in children residing in areas of petroleum-refining, petrochemical, and chemical industries. A total of 4816 children aged 3 to 14 years who lived in Ufa areas differing in the level and nature of ambient air pollution were examined. Those living in the poorer ecological areas (high total pollution and levels of chlorinated hydrocarbons, formaldehyde, and phenol) had more commonly gastroenterological diseases with prevailing hepatobiliary disorders in the pattern of diseases. The specific features of the diseases in these children are earlier onset, more frequent recurrences, more prolonged exacerbations involving other organs and systems than in those living in more favourable areas.


Estrogen protects against brain lipid peroxidation in ethanol-withdrawn rats.
This study examined whether 17beta-estradiol (E2) administration protects against ethanol withdrawal (EW)-associated oxidative insults by assessing oxidative markers thiobarbituric-acid-reacting-substances (TBARS). Ovariectomized rats implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5% wt./vol., 5 weeks) or control dextrin diet (Dextrin/Oil). At 24 or 48 h of EW, rats were tested for overt EW signs and the cerebellum, hippocampus, and cortex were prepared for TBARS assessment in the presence and absence of FeCl3. For control experiments, we assessed E2 effects on blood ethanol concentrations and TBARS levels during ethanol exposure prior to EW. The EW/Oil group showed enhanced endogenous- and FeCl3-stimulated membrane TBARS levels in the cerebellum and hippocampus in a manner inhibited by E2 treatment. There was a relationship between the severity of EW and elevation of TBARS levels, particularly in the cerebellum. The enhanced TBARS levels at 24 h of EW appeared to diminish at 48 h in the hippocampus, but persisted in the cerebellum. E2 treatment did not alter blood ethanol concentrations and ethanol exposure alone did not enhance TBARS levels. These data suggest that EW rather than ethanol enhances brain lipid peroxidation that is transient and brain-region specific. Estrogens protect against the brain lipid peroxidation in a manner independent of blood ethanol concentrations.


Growth and stability of ZnTe magic-size nanocrystals.
A synthetic method for ZnTe magic-sized clusters (MSCs) is reported, and the stability and growth kinetics of these clusters are investigated. Four distinct MSC families, with lowest-energy absorption peaks at 330, 354, 378, and 392 nm, are observed. The stability and growth kinetics of the MSCs are strongly influenced by the reaction temperature, precursor concentration, and nature of the ligands used as the coordinating solvent. High precursor concentrations result in faster growth and MSC formation at lower temperatures. Higher temperatures accelerate the growth kinetics and lead to a gradual shift from the stepwise MSC growth regime to a continuous growth regime. For temperatures above 260 °C, only continuous growth of nanocrystals is observed. The nature of the ligands also influences the stability and growth of ZnTe MSCs, which are formed with primary alkylamines as ligands, but not when trioctylphosphine, trioctylphosphine oxide, or trioctylamine are used as the sole ligands. This demonstrates the crucial role of ligands in the formation of stable ZnTe MSCs using colloidal synthetic methods. Under optimal synthetic conditions (200 °C, hexadecylamine as ligand, and suitable precursor concentrations), the method presented here allows the synthesis and isolation of a single MSC family absorbing at 330 nm.


An approach for searching genes in signaling pathways or gene-gene interaction networks related to Hypertension in the Mexican population.
The selection of single nucleotide polymorphisms (SNPs) to evaluate the genetic susceptibility in complex traits is often conducted in isolation, without considering the entire set of genes. Incorporating signaling pathways or gene-gene interaction search may provide a more comprehensive approach to selecting SNP candidates for further study. To propose a systematic procedure for identifying SNPs candidates with complex traits such as hypertension and blood pressure. Sequential stages to SNPs selection: 1) literature review to identify SNPs, following the PRISMA methodology, 2) identification and selection of signaling pathways and selection of gene-gene interaction networks using the STRING software, and 3) application of specific criteria for SNPs candidates, including: a) SNPs with minor allele frequency > 5% in the target population, b) SNPs located within genes involved in three or more signaling pathways, and c) SNPs that are not in linkage disequilibrium, with a D'or r2 value < 0.8. Stage 1) A total of 44 publications were selected, providing information on 230 genes evaluated with blood pressure. Stage 2) Using the STRING software, we selected 7 signaling pathways with a false discovery rate < 0.0001 and strength ≥ 0.8; and we identified 16 genes belonging to gene-gene interaction networks, six of them share ≥ 3 signaling pathways. Stage 3) Finally, 7 SNPs were selected for genotyping in the Health Workers Cohort Study. We observed a positive association between SNPs with hypertension incidence in males (rs1130214, rs3807989) and females (rs5051, rs2493123). Our methodological proposal may be a reliable way for selecting SNPs candidates to study complex traits.


Prevalence, associated factors, and prognostic determinants of AIDS-related toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy.
Characteristics, associated factors, and survival probability of toxoplasmic encephalitis (TE) in the era of advanced highly active antiretroviral therapy (HAART) have not been fully clarified. Data for 205 individuals with acquired immunodeficiency syndrome (AIDS)-related TE were derived from the Italian Registry Investigative NeuroAIDS database, and the cases were studied longitudinally to evaluate prevalence, clinical characteristics, and survival. Moreover, the relationship between the occurrence of TE and exposure to antiretroviral therapy and to TE prophylaxis was evaluated. With an overall prevalence of 26%, TE represented the most frequent neurological disorder in the cohort. Female sex, severe immunodeficiency, and absence of primary TE prophylaxis significantly increased the risk of TE, and previous exposure to antiretroviral therapy reduced the probability of disease occurrence. Thirty-six percent of patients who had received antiretroviral therapy developed TE, although in most of these cases, the patient experienced failure of antiretroviral therapy. Of note, 66% of patients who had experienced antiretroviral therapy did not receive prophylaxis for TE at TE diagnosis. The 1-year probability of that infection with human immunodeficiency virus (HIV) would progress or that death would occur after TE was 40% and 23%, respectively. Cognitive symptoms, low CD4(+) cell count, not receiving HAART after TE, and initiating HAART >2 months after TE diagnosis were all significantly associated with an increased probability of progression of HIV infection. Not receiving HAART after diagnosis negatively affected survival. TE remains a highly prevalent disorder of the central nervous system, even in the late HAART era, particularly among severely immunosuppressed patients and in absence of prophylaxis. Considering that persons with TE have a high probability of early death, prophylaxis should be maintained in immunosuppressed patients who experience failure of antiretroviral therapy, and HAART should be initiated as soon as possible after TE diagnosis.


Interface between graphene and liquid Cu from molecular dynamics simulations.
Controllable synthesis of defect-free graphene is crucial for applications since the properties of graphene are highly sensitive to any deviations from the crystalline lattice. We focus here on the emerging use of liquid Cu catalysts, which have high potential for fast and efficient industrial-scale production of high-quality graphene. The interface between graphene and liquid Cu is studied using force field and ab initio molecular dynamics, revealing a complete or partial embedding of finite-sized flakes. By analyzing flakes of different sizes, we find that the size-dependence of the embedding can be rationalized based on the energy cost of embedding vs bending the graphene flake. The embedding itself is driven by the formation of covalent bonds between the under-coordinated edge C atoms and the liquid Cu surface, which is accompanied by a significant charge transfer. In contrast, the central flake atoms are located around or slightly above 3 Å from the liquid Cu surface and exhibit weak van der Waals-bonding and much lower charge transfer. The structural and electronic properties of the embedded state revealed in our work provide the atomic-scale information needed to develop effective models to explain the special growth observed in experiments where various interesting phenomena such as flake self-assembly and rotational alignment, high growth speeds, and low defect densities in the final graphene product have been observed.


Sensitivity analysis: from model parameters to system behaviour.
Sensitivity analysis addresses the manner in which model behaviour depends on model parametrization. Global sensitivity analysis makes use of statistical tools to address system behaviour over a wide range of operating conditions, whereas local sensitivity analysis focuses attention on a specific set of nominal parameter values. This narrow focus allows a complete analytical treatment and straightforward interpretation in the local case. Sensitivity analysis is a valuable tool for model construction and interpretation, and can be applied in medicine and biotechnology to predict the effect of interventions.


Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels: a genome-wide study.
Zinc is an essential metal that, when in excess, can be deleterious to the cell. Therefore, homeostatic mechanisms for this cation must be finely tuned. To better understand the response of yeast in front of an excess of zinc, we screened a systematic deletion mutant library for altered growth in the presence of 6 mM zinc. Eighty-nine mutants exhibited increased zinc sensitivity, including many genes involved in vacuolar assembling and biogenesis. Interestingly, a mutant lacking the Aft1 transcription factor, required for the transcriptional response to iron starvation, was found to be highly sensitive to zinc. Genome-wide transcriptional profiling revealed that exposure to 5 mM ZnCl(2) results in rapid increase in the expression of numerous chaperones required for proper protein folding or targeting to vacuole and mitochondria, as well as genes involved in stress response (mainly oxidative), sulphur metabolism and some components of the iron regulon. The effect of the lack of Aft1 both in the absence and in the presence of zinc overload was also investigated. Exposure to high zinc generated reactive oxygen species and markedly decreased glutathione content. Interestingly, zinc excess results in decreased intracellular iron content and aconitase and cytochrome c activities in stationary-phase cultures. These findings suggest that high zinc levels may alter the assembly and/or function of iron-sulphur-containing proteins, as well as the biosynthesis of haem groups, thus establishing a link between zinc, iron and sulphur metabolism.


Association of CTLA-4 Gene Variants with Response to Therapy and Long-term Survival in Metastatic Melanoma Patients Treated with Ipilimumab: An Italian Melanoma Intergroup Study.
Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of patients with metastatic melanoma (MM). We investigated the association of CTLA-4 single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS in a cohort of 173 MM patients. Patients were genotyped for six CTLA-4 SNVs (-1661A>G, -1577G>A, -658C>T, -319C>T, +49A>G, and CT60G>A). We assessed the association between SNVs and BOR through multinomial logistic regression (MLR) and the prognostic effect of SNVs on OS through Kaplan-Meier method. Both -1577G>A and CT60G>A SNVs were found significantly associated with BOR. In particular, the proportion of responders was higher in G/G genotype while that of stable patients was higher in A/A genotype. The frequency of patients experiencing progression was similar in all genotypes. MLR evidenced a strong downward trend in the probability of responsiveness/progression, in comparison to disease stability, as a function of the allele A "dose" (0, 1, or 2) in both SNVs with reductions of about 70% (G/A vs G/G) and about 95% (A/A vs G/G). Moreover, -1577G/G and CT60G/G genotypes were associated with long-term OS, the surviving patients being at 3 years 29.8 and 30.8%, respectively, as compared to 12.9 and 14.4% of surviving patients carrying -1577G/A and CT60G/A, respectively. MM patients carrying -1577G/G or CT60G/G genotypes may benefit from IPI treatment in terms of BOR and long-term OS. These CTLA-4 SNVs may serve as potential biomarkers predictive of favorable outcome in this subset of patients.


Classic signs in uroradiology.
The language of radiology is rich with descriptions of imaging findings, often metaphorical, which have found common usage in the day-to-day practice of genitourinary radiology. These "classic signs" give us confidence in our diagnosis. Some of the signs have become so familiar to us that they are referred to as an "Aunt Minnie." When the sign is invoked, or an Aunt Minnie is recognized, it often brings an impression of the image to mind, and it may have specific diagnostic and pathologic implications. The article uses classic signs accumulated from the literature to review a variety of pathologic conditions in the urinary tract.


Evaluation of curcumin for dermatologic conditions: a systematic review.
There is increasing demand for natural and sustainable products for the treatment of dermatologic conditions. This systematic review aims to critically analyze published randomized controlled trials (RCTs) and provide evidence-based recommendations on the therapeutic use of curcumin for a variety of dermatological diseases. A systematic search of published literature was performed on July 18, 2023 using PRISMA guidelines for turmeric or curcumin for the treatment of skin diseases. Clinical recommendations were made based on the Oxford Centre for Evidence-Based Medicine guidelines. We identified 18 original randomized controlled trials for use of turmeric or curcumin for psoriasis, radiation dermatitis, oral lichen planus, pruritis, vitiligo, tinea capitis, facial erythema, and scarring. Psoriasis, cesarean section scar, and pruritus received grade of recommendation B. Radiation dermatitis, oral lichen planus, vitiligo, tinea capitis, and facial redness received grade of recommendation C or D. Curcumin was demonstrated to have an excellent safety profile in all clinical trials analyzed. Further research is required to determine optimal dosing and treatment parameters of turmeric. Additional, larger, RCTs and non-RCTs should be conducted to further investigate the safety and efficacy of curcumin as a treatment option for dermatological diseases.


Development and characterization of a human B cell line that responds to B cell growth factor but not interleukin 2.
The human lymphoblastoid cell line we present here proliferated in response to a 14,000 m.w. B cell growth factor (BCGF), and not to interleukin 2 (IL 2). This cell line, designated B-A3, was established by Epstein Barr virus (EBV) transformation of Staphylococcus aureus Cowan I (SAC)-activated spleen B cells, and has been maintained in RPMI 1640 medium complemented with 15% fetal calf serum (FCS) without the addition of other exogenous growth factors. A proliferative response, as measured by [3H]thymidine uptake of B-A3 cells was significantly induced by either commercial IL 2-free human BCGF preparations, or phytohemagglutinin-stimulated mixed lymphocyte culture supernatant at all FCS concentrations used in the assay. The most marked proliferation due to BCGF, however, was observed in the absence of FCS. This BCGF-induced proliferation was not influenced by IL 2 or interferon-gamma (IFN-gamma), because both recombinant IL 2 and IFN-gamma failed to induce proliferation. The response of B-A3 cells to a specific BCGF was additionally indicated by the responsiveness of this cell line to BCGF purified by a series of chromatographic steps. The BCGF to which B-A3 cells responded had a m.w. of 14,000 and was similar to low m.w. BCGF reported from other laboratories. Surface characterization of B-A3 cells, analyzed by flow cytometry with a panel of monoclonal antibodies, demonstrated that the majority of B-A3 cells were stained positively with Leu-12, HLA-DR, and surface IgG markers, whereas staining with surface IgM, IgD markers, pan T cell markers (Leu-4 and Leu-9), and IL 2 receptor (Tac) were consistently negative. Taken together, the human lymphoblastoid cell line we present here responded specifically to a low m.w. BCGF. This cell line may be of value in the purification of BCGF to homogeneity, in studies of the interactions of BCGF with human B cells, and in the identification of the BCGF receptor.


Prevalence and risk factors of valvular calcification in hemodialysis patients.
Valvular abnormalities frequently occur in patients with chronic kidney failure. This study evaluated the prevalence of heart valve calcification (HVC) in hemodialysis patients and factors associated with it. Medical charts of 129 hemodialysis patients were reviewed retrospectively. Demographic features and laboratory analysis of the patients were systematically recorded. Echocardiographic findings were collected, including ejection fraction, aortic valve calcification (AVC), mitral valve calcification (MVC), left ventricle mass, left ventricle mass index, and pulmonary artery pressure. Valvular abnormalities were found in 43 patients (33.3%); 30 patients (23.3%) had MVC, 28 (21.7%) had AVC, and 15 (11.6%) had both MVC and AVC. Patients with HVC were older than other patients (P < .001). On echocardiography, higher left ventricle mass, left ventricle mass index, and pulmonary artery pressure levels were found in patients with HVC. Regarding the lipid profile, serum calcium, serum phosphorus, calcium-phosphorus product, and parathyroid hormone concentrations, there were no significant differences between patients with and without HVC. Ejection fraction levels were significantly lower in patients with HVC (P = .002) and serum albumin level of patients with HVC was significantly diminished. This study failed to show an association between HVC in hemodialysis patients and calcium-phosphorus product and parathyroid hormone levels; however, age and diabetes mellitus could be regarded as risk factors. In addition, HVC may lead to increased left ventricle mass index and pulmonary artery pressure and decreased ejection fraction, and low albumin levels may be attributable to inflammation.


Synovial hemangioma of the knee joint in a 12-year-old boy: a case report.
Synovial hemangioma is a rare condition and is frequently misdiagnosed, leading to a diagnostic delay of many years. We present a case of an atypical synovial hemangioma in a 12-year-old Caucasian boy with a diagnostic delay of 3 years. It is important to know that synovial hemangioma mostly affects the knee joint, showing recurrent bloody effusions without a history of trauma. If there are no intermittent effusions, the diagnosis will be even more difficult. In cases of nonspecific symptoms and longstanding knee pain the diagnosis of a synovial hemangioma should also be considered in order to avoid diagnostic delay. Magnetic resonance imaging is the main diagnostic tool to evaluate patients with synovial hemangioma, showing characteristic lace-like or linear patterns.Angiography can identify feeder vessels and offers the possibility of embolisation in the same setting. Surgical excision, either done per arthroscopy or per arthrotomy, is recommended as soon as possible to avoid the risk of damage to the cartilage.


Defining potentially conserved RNA regulons of homologous zinc-finger RNA-binding proteins.
Glucose inhibition of gluconeogenic growth suppressor 2 protein (Gis2p) and zinc-finger protein 9 (ZNF9) are conserved yeast and human zinc-finger proteins. The function of yeast Gis2p is unknown, but human ZNF9 has been reported to bind nucleic acids, and mutations in the ZNF9 gene cause the neuromuscular disease myotonic dystrophy type 2. To explore the impact of these proteins on RNA regulation, we undertook a systematic analysis of the RNA targets and of the global implications for gene expression. Hundreds of mRNAs were associated with Gis2p, mainly coding for RNA processing factors, chromatin modifiers and GTPases. Target mRNAs contained stretches of G(A/U)(A/U) trinucleotide repeats located in coding sequences, which are sufficient for binding to both Gis2p and ZNF9, thus implying strong structural conservation. Predicted ZNF9 targets belong to the same functional categories as seen in yeast, indicating functional conservation, which is further supported by complementation of the large cell-size phenotype of gis2 mutants with ZNF9. We further applied a matched-sample proteome-transcriptome analysis suggesting that Gis2p differentially coordinates expression of RNA regulons, primarily by reducing mRNA and protein levels of genes required for ribosome assembly and by selectively up-regulating protein levels of myosins. This integrated systematic exploration of RNA targets for homologous RNA-binding proteins indicates an unexpectedly high conservation of the RNA-binding properties and of potential targets, thus predicting conserved RNA regulons. We also predict regulation of muscle-specific genes by ZNF9, adding a potential link to the myotonic dystrophy related phenotypes seen in ZNF9 mouse models.


Long-term outcomes after contaminated complex abdominal wall reconstruction.
Complex abdominal wall repair (CAWR) in a contaminated operative field is a challenge. Available literature regarding long-term outcomes of CAWR comprises studies that often have small numbers and heterogeneous patient populations. This study aims to assess long-term outcomes of modified-ventral hernia working group (VHWG) grade 3 repairs. Because the relevance of hernia recurrence (HR) as the primary outcome for this patient group is contentious, the need for further hernia surgery (FHS) was also assessed in relation to long-term survival. A retrospective cohort study with a single prospective follow-up time-point nested in a consecutive series of patients undergoing CAWR in two European national intestinal failure centers. In long-term analysis, 266 modified VHWG grade 3 procedures were included. The overall HR rate was 32.3%. The HR rates for non-crosslinked biologic meshes and synthetic meshes when fascial closure was achieved were 20.3% and 30.6%, respectively. The rates of FHS were 7.2% and 16.7%, and occurred only within the first 3 years. Bridged repairs showed poorer results (fascial closure 22.9% hernia recurrence vs bridged 57.1% recurrence). Overall survival was relatively good with 80% en 70% of the patients still alive after 5 and 10 years, respectively. In total 86.6% of the patients remained free of FHS. In this study of contaminated CAWR, non-crosslinked biologic mesh shows better results than synthetic mesh. Bridging repairs with no posterior and/or anterior fascial closure have a higher recurrence rate. The overall survival was good and the majority of patients remained free of additional hernia surgery.


Nanostructured porous silicon micropatterns as a tool for substrate-conditioned cell research.
The localized irradiation of Si allows a precise patterning at the microscale of nanostructured materials such as porous silicon (PS). PS patterns with precisely defined geometries can be fabricated using ion stopping masks. The nanoscale textured micropatterns were used to explore their influence as microenvironments for human mesenchymal stem cells (hMSCs). In fact, the change of photoluminescence emission from PS upon aging in physiological solution suggests the intense formation of silanol surface groups, which may play a relevant role in ulterior cell adhesion. The experimental results show that hMSCs are sensitive to the surface micropatterns. In this regard, preliminary β-catenin labeling studies reveal the formation of cell to cell interaction structures, while microtubule orientation is strongly influenced by the selective adhesion conditions. Relevantly, Ki-67 assays support a proliferative state of hMSCs on such nanostructured micropatterns comparable to that of standard cell culture platforms, which reinforce the candidature of porous silicon micropatterns to become a conditioning structure for in vitro culture of HMSCs.


Photodissociation dynamics of halogenated aromatic molecules: the case of core-ionized tetrabromothiophene.
We studied the gas-phase photodissociation of a fully halogenated aromatic molecule, tetrabromothiophene, upon core-shell ionization by using synchrotron radiation and energy-resolved multiparticle coincidence spectroscopy. Photodynamics was initiated by the selective soft X-ray ionization of three elements - C, S, and Br - leading to the formation of dicationic states by Auger decay. From a detailed study of photodissociation upon Br 3d ionization, we formulate a general fragmentation scheme, where dissociation into neutral fragments and a pair of cations prevails, but dicationic species are also produced. We conclude that dicationic tetrabromothiophene typically undergoes deferred charge separation (with one of the ions being often Br+) that may be followed by secondary dissociation steps, depending on the available internal energy of the parent dication. Observations suggest that the ejection of neutral bromine atoms as the first step of deferred charge separation is a prevailing feature in dicationic dissociation, although sometimes in this step the C-Br bonds appear to remain intact and the thiophene ring is broken instead. Ionization-site-specific effects are observed particularly in doubly charged fragments and as large differences in the yields of the intact parent dication. We interpret these effects, using first-principles calculations and molecular dynamics simulations of core-hole states, as likely caused by the geometry changes during the core-hole lifetime.


Better Together: Outcomes of Cooperation Versus Competition in Social Exergaming.
Children and adolescents most often play active videogames, or exergames, in a social environment. Social play may enhance the potential benefits of an exergaming experience, much like group exercise and team sports are observed to improve physical activity-related outcomes above those of solitary exercise. Two ubiquitous elements of exergames are cooperation and competition. Previous literature suggests that cooperative and competitive aspects of exergames may affect physiological and psychosocial changes. Competitive play has been found to increase energy expenditure and aggression in short bouts of exergaming. Cooperative exergaming has been found to increase motivation, promote continued play, enhance self-efficacy, and increase pro-social behaviors. In one study, a cooperative exergaming condition also resulted in significant weight loss for overweight and obese adolescents. Individual player differences such as individual preferences, competitiveness, weight status, age, gender, and ethnicity may moderate effects. Although the current volume of literature on competition and cooperation in exergaming is small, social exergames hold promise as an engaging alternative to traditional physical activity interventions and may promote a broad range of positive outcomes for children and adolescents. Principles of cooperation and competition are applicable for developers of health-promoting games. Future research is needed to further understand the mechanisms of how competition and cooperation in social exergaming impact physiological and psychosocial outcomes.


High expression of Y-box-binding protein 1 is associated with local recurrence and predicts poor outcome in patients with colorectal cancer.
Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. Novel prognostic biomarkers are urgently warranted to help improve the treatment of CRC. Y-box-binding protein 1 (YB-1) has been identified as a multifunctional oncoprotein in various malignancies. Our previous study has suggested that YB-1 may promote malignant progression of CRC cells in vitro. However, its clinical and prognostic significance in CRC patients remains unclear. In this study, the expression of YB-1 was examined in 32 fresh CRC tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and in 170 paraffin-embedded CRC tissues using immunohistochemistry. The result of qRT-PCR demonstrated mRNA expression of YB-1 was increased in 26 of 32 (81.25%) of CRC patients. The statistical analysis based on immunohistochemical staining suggested that YB-1 expression was significantly correlated with tumor differentiation, tumor invasion, lymph node metastasis and Dukes' classification (all P<0.05). Furthermore, we found that patients with high YB-1 expression had a poorer prognosis and were more likely to undergo local recurrence, compared to those with low YB-1 expression. We also identified that YB-1 expression, together with lymph node metastasis and Dukes' classification were independent prognostic factors for CRC patients. In conclusion, our study for the first time demonstrated the clinical and prognostic significance of YB-1 in CRC and suggested that YB-1 is of great potential to be an attractive therapeutic target as well as prognostic biomarker for CRC patients.


[Dependence of the thoracic abdominal ratio of the respiration parameters on body positioning relative to the vector of gravity].
Abdominal and thoracic functional reserves of respiration and level of their involvement in spontaneous breathing were investigated in 10 male volunteers aged 20 to 22 put in horizontal head-down (-7 degrees and -30 degrees) or orthostatic (+70 degrees) position. The thoracic-abdominal functional reserves of respiration dependent on the spatial positioning of the body were found to be the factor that determines magnitude of contribution of the thorax and diaphragm in the breathing volume.