Circular dichroism and thermal melting differentiation of Hoechst 33258 binding to the curved (A(4)T(4)) and straight (T(4)A(4)) DNA sequences.
The ability of the B-DNA minor groove ligand Hoechst 33258 to discriminate between prototype curved and straight duplex DNA sequences was investigated by circular dichroism (CD) titrations at the wavelengths of absorbance of the ligand. The sequences were studied either within the framework of the ligated decamers (CA(4)T(4)G)(n) and (CT(4)A(4)G)(n), or within that of the single dodecamers GCA(4)T(4)GC and GCT(4)A(4)GC, to confirm and extend our earlier results based on fluorescence titrations of ligated decamers. A unique, strong binding site is invariantly present in both sequence units. The binding affinity of the drug for the site in the curved A(4)T(4) sequence was found 3- to 4-fold higher compared to the straight sequence. All these features hold true irrespective of the sequence framework, thus confirming that they reflect specific properties of the binding to the two sequences. Ligand binding increases the thermal stability of straight and curved duplex dodecamers to the same extent, thus maintaining the melting temperature differential between the two sequences. However, the different melting patterns and the difference between [total ligand]:[site] ratios needed for site saturation in the two duplexes are in agreement with the difference between binding constants derived from CD measurements.


Current concepts and issues in blood management.
Blood management in orthopedic surgery is no longer an option; it is a requirement. The combination of patient desire to avoid transfusion, increasing evidence of multiple risks, decreasing blood supplies, and increasing costs mandate attention. This article addresses the balance of risk versus benefit in blood transfusion and presents a perioperative plan of blood management for patients undergoing orthopedic surgery.


Parallel generation of easily selectable multiple nephronal cell types from human pluripotent stem cells.
Human pluripotent stem cells (hPSCs) provide a source for the generation of defined kidney cells and renal organoids applicable in regenerative medicine, disease modeling, and drug screening. These applications require the provision of hPSC-derived renal cells by reproducible, scalable, and efficient methods. We established a chemically defined protocol by application of Activin A, BMP4, and Retinoic acid followed by GDNF, which steered hPSCs to the renal lineage and resulted in populations of SIX2+/CITED1+ metanephric mesenchyme- (MM) and of HOXB7+/GRHL2+ ureteric bud (UB)-like cells already by 6 days. Transcriptome analysis corroborated that the PSC-derived cell types at day 8 resemble their renal vesicle and ureteric epithelial counterpart in vivo, forming tubular and glomerular renal cells 6 days later. We demonstrate that starting from hPSCs, our in vitro protocol generates a pool of nephrogenic progenitors at the renal vesicle stage, which can be further directed into specialized nephronal cell types including mesangial-, proximal tubular-, distal tubular, collecting duct epithelial cells, and podocyte precursors after 14 days. This simple and rapid method to produce renal cells from a common precursor pool in 2D culture provides the basis for scaled-up production of tailored renal cell types, which are applicable for drug testing or cell-based regenerative therapies.


CGM, Pregnancy, and Remote Monitoring.
The glycemic goals of pregnancy are very narrow to reduce excess risks for numerous maternal and fetal complications. Continuous glucose monitors (CGMs) may help women achieve glucose goals and reduce hypoglycemia. CGM use has been found to be safe and effective in pregnancies associated with diabetes. CGM use can accurately identify glycemic patterns among women with and without diabetes in pregnancy. The data on the effects of CGM use on maternal and fetal outcomes are conflicting. Using CGMs in conjunction with continuous subcutaneous insulin infusion therapy in pregnancies complicated by diabetes may improve outcomes. There are limitations of CGM use that affect patients in and outside of pregnancy, as well as specific barriers that only affect pregnant women. Of importance, CGM use does not replace standard clinical care, but may be used an adjunctive tool in pregnancy. CGM remote monitoring in pregnancy is an understudied field. In this study, we review the studies on CGM use in pregnancy.


A new paradigm for plaque stabilization.
The concept of plaque stabilization was developed to explain how lipid lowering could decrease adverse coronary events without a substantial reduction in the regression of atherosclerosis. Plaques were stabilized by reducing serum cholesterol leading to several favorable pathobiological changes in the vessel wall of lipid-rich plaques responsible for a majority of acute coronary events. However, this concept is limited for several reasons including that it does not incorporate strategies directed against either plaques that have already destabilized or non-lipid-rich plaques, which are the substrate for at least one third of major coronary thrombi and may or may not be stabilized by lipid lowering. For the destabilized plaque with overlying thrombus, either percutaneous intervention, long-term antithrombotic and/or anticoagulant therapy, or possibly aggressive lipid lowering stabilizes lesions by reducing subsequent thrombosis at the lesion site and, at least with lipid lowering, by improving endothelial function and possibly reducing inflammation. Short-term, in-hospital antithrombotic approaches alone with agents like the GP platelet IIb/IIIa inhibitors have not been effective in this situation. For other plaques not presently destabilized, the main goal of therapy is reducing future acute coronary events. Several classes of drugs, including ACE inhibitors, beta-blockers, and antithrombotic agents in addition to lipid-lowering agents, reduce events, and this may be attributable, at least in part, to plaque-stabilizing effects.


Quantitative management techniques in dietetics: improving practice through technology transfer.
A content analysis of articles appearing chronologically in the Journal of The American Dietetic Association since its inception in 1925 reveals the breadth and depth of management practice in the dietetic profession. This historical review highlights the introduction, demonstration, and adoption of management tools and techniques in the profession, with particular emphasis on quantitative management science techniques. Seven classifications of management science techniques were used for the content analysis. Although applications of forecasting, simulation, linear programming, and queuing models have been reported in the Journal, a gap is evident between the demonstration of management science techniques and operational use of these techniques in dietetic practice. Dietetic researchers, practitioners, and educators have vital roles in facilitating the transfer of quantitative management science technology into operational dietetic practice. Assessment of the state-of-the-art of dietetic management practice relative to proven quantitative management science techniques reveals the need for improved technology transfer to enhance professional ability in both tactical and strategic decision making.


Ocular presentation of Wegener granulomatosis.
A 55-year-old woman presented with swelling of the right upper and lower eyelid, diplopia and proptosis. The clinical findings combined with imaging, pathology and full internal work-up allowed to make a diagnosis of limited Wegener granulomatosis. Treatment with systemic corticosteroids and cyclophosphamide markedly decreased the orbital swelling and diplopia.


Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts.
The Shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. While many aspects of Shigella colonic cell invasion are known, crucial gaps in knowledge regarding how the bacteria survive, transit, and regulate gene expression prior to infection remain. In this study, we define mechanisms of resistance to bile salts and build on previous research highlighting induced virulence in Shigella flexneri strain 2457T following exposure to bile salts. Typical growth patterns were observed within the physiological range of bile salts; however, growth was inhibited at higher concentrations. Interestingly, extended periods of exposure to bile salts led to biofilm formation, a conserved phenotype that we observed among members of the Enterobacteriaceae Characterization of S. flexneri 2457T biofilms determined that both bile salts and glucose were required for formation, dispersion was dependent upon bile salts depletion, and recovered bacteria displayed induced adherence to HT-29 cells. RNA-sequencing analysis verified an important bile salt transcriptional profile in S. flexneri 2457T, including induced drug resistance and virulence gene expression. Finally, functional mutagenesis identified the importance of the AcrAB efflux pump and lipopolysaccharide O-antigen synthesis for bile salt resistance. Our data demonstrate that S. flexneri 2457T employs multiple mechanisms to survive exposure to bile salts, which may have important implications for multidrug resistance. Furthermore, our work confirms that bile salts are important physiological signals to activate S. flexneri 2457T virulence. This work provides insights into how exposure to bile likely regulates Shigella survival and virulence during host transit and subsequent colonic infection.


Cerebral vasospasm resulted in "stent shortening" after pipeline assisted coil embolization for blood blister aneurysms.
Blood blister aneurysms (BBAs) are intracranial arterial lesions appearing in nonbranching sites of the supraclinoid internal carotid artery as well as the basilar artery. Endovascular treatment of BBAs is still not well established because of the rarity of these lesions. We report incidences of BBAs with associated vasospasms. Treatment of the BBAs and associate vasospasms with single Pipeline Flex embolization device (PLED) assisted coiling resulted in seemly shorting of the PLEDs in 3 patients.A retrospective analysis of patients with BBAs who were treated with single PLED assisted coiling from July 2018 to October 2019 was conducted. Patients' ethnic and medical records, aneurysmal characteristics, intraoperative-rupture, cerebral vasospasm (CVS), postprocedure contrast filling, follow-up imaging, and results were analyzed. Neurological examination at baseline and outcome based on modified Rankin scale (mRS) at discharge as well as follow-ups were also documented.Six patients consisting of 5 females and 1 male, with a mean age of 48.3 years (range from 34-67) were identified during our analysis. All the BBAs were located in nonbranching site of supra-clinoidal segment of internal carotid artery with a mean neck width of 4.5 mm and mean aneurysm size of 4.23 mm. PLED assisted coiling's were performed in all of them. CVS was observed in 3 patients while 1 patient had an intraoperative-rupture of the BBA. Postprocedure contrast filling was still present in 1 patient. All the patients had good outcomes with discharge and follow-up mRS scores ≤ 2 except 1 patient with mRS score = 3 with aphasia.PLED assisted endovascular coiling is very safe and efficient in treating patients with BBAs. Resolution of CVSs after treatment made the PLEDs seemly shorter. Furthermore, a combination of arterial lengthening after gaining their tensile strength back and radical expansion of the PLED could account for the shortening.


The question of differences in body dimensions between children from endogamic and exogamic matings: a study in Sardinia.
The aim of this study is to investigate whether there are differences in body dimensions between children of the same sex from endogamic and exogamic matings. The cross-sectional sample consisted of 285 children, 136 males and 149 females, 6 to 10 years old, attending elementary schools in Tortolí, a town in east-central Sardinia. The children of each sex were divided into two groups: endogamic and exogamic, the first including children from parents born in the same Sardinian village, the latter children from parents born in two different places. For each sex, ANCOVA with age as covariate revealed no significant differences between the two groups of children for the 35 anthropometric variables considered. Moreover, for each sex, there were no significant differences between the two groups of children for some anthropometric variables considered to be indicators of nutritional status: sums of skinfold thicknesses, waist/hip ratio, body mass index, total upper arm area, upper muscle arm area, upper arm fat area. We conclude that when Sardinian children of endogamous and exogamous unions are in similar nutritional conditions, they do not differ in body dimensions.


[The tissue and cell defense mechanisms of the oral mucosa].
The modern concepts of tissue and cell defense mechanisms in oral mucosa are discussed. These mechanisms include (a) physical barriers (of epithelium and lamina propria), (b) non-specific antimicrobial humoral factors, (c) non-specific cellular defense mechanisms, (d) specific immune humoral and cell-mediated defense mechanisms, (c) saliva, containing both non-specific and specific antimicrobial factors. Special reference is given to antigen-presenting dendritic cells and various lymphocyte subpopulations both in epithelium and in lamina propria. The interaction of different cell and tissue defense mechanisms and their regional variations are briefly characterized.


Competitive counterion complexation allows the true host : guest binding constants from a single titration by ionic receptors.
Counterion competitive complexation is a background process currently ignored by using ionic hosts. Consequently, guest binding constants are strongly affected by the design of the titration experiments in such a way that the results are dependent on the guest concentration and on the presence of added salts, usually buffers. In the present manuscript we show that these experimental difficulties can be overcome by just considering the counterion competitive complexation. Moreover a single titration allows us to obtain not only the true binding constants but also the stoichiometry of the complex showing the formation of 1 : 1 : 1 (host : guest : counterion) complexes. The detection of high stoichiometry complexes is not restricted to a single titration experiment but also to a displacement assay where both competitive and competitive-cooperative complexation models are taken into consideration.


rac-2-tert-Butyl-2,4,5,6,6-penta-chloro-cyclo-hex-3-en-1-one.
The title compound, C(10)H(11)Cl(5)O, is a chiral mol-ecule with two stereogenic centres. However, it crystallizes as a racemate. One of enanti-omers reveals the relative configuration (2S*,5R*). The cyclo-hexene ring adopts a half-chair conformation.


Synthesis and in-situ TEM transport measurements of individual GaN nanowires and nanotubes.
High-purity GaN nanowires and nanotubes of various morphologies and sizes have been synthesized through epitaxial growth on [001]-oriented sapphire substrates. The GaN nanowires grown on Ni catalyst particles possess an average diameter of approximately 100 nm and rather smooth surface; whereas GaN nanotubes guided by Au particles exhibit large diameters (100-500 nm) and rough surface morphology. The microstructures and crystallography of GaN nanowires and nanotubes were analyzed using a high-resolution transmission electron microscope (HRTEM). For the first time the electrical transport in individual GaN nanowires and nanotubes was in-situ measured inside the microscope. The electrical transport was mainly affected by the nanocrystal quality and nanostructure/contact interfaces.


Insights into the Toxicity of Triclosan to Green Microalga Chlorococcum sp. Using Synchrotron-Based Fourier Transform Infrared Spectromicroscopy: Biophysiological Analyses and Roles of Environmental Factors.
This study investigated the toxicity of triclosan to the green microalga Chlorococcum sp. under multiple environmental stressors. The interactions between triclosan and environmental stressors were explored through full two-way factorial, synchrotron-based Fourier transform infrared spectromicroscopy and principal component analyses. Phosphorus concentration, pH * phosphorus concentration, and temperature * pH * NaCl concentration were the most statistically significant factors under triclosan exposure. The variation of those factors would have a huge impact on biophysiological performances. It is interesting to find Chlorococcum sp. may become more resistant against triclosan in phosphorus-enriched environment. Besides, particular significant factors from multiple environmental stressors showed the impacts of triclosan on the corresponding response of Chlorococcum sp. owing to the specific structure and performance of biomolecular components. Moreover, two high-order interactions of temperature * pH * NaCl concentration and temperature * pH * NaCl concentration * phosphorus concentration had more contributions than others at the subcellular level, which could be attributed to the interactive complexity of biomolecular components. Due to cellular self-regulation mechanism and short exposure time, the biophysiological changes of Chlorococcum sp. were undramatic. These findings can help reveal the interactive complexity among triclosan and multiple environmental stressors. It is suggested that multiple environmental stressors should be considered during ecological risk assessment and management of emerging pollutants.


[Late diagnosis of malignant renal tumors. Review and case reports (author's transl)].
In this paper the problem of early diagnosis in hypernephroid carcinoma of the kidney is explained. Hematuria remains inspite of other possible causes suspect for tumor as long as a tumor is certainly excluded. The different methods for diagnostic and characteristic signs for tumor in the X-ray (EVP) are discussed. Three cases of late diagnosis of hypernephroid carcinoma of the kidney, due to long time not explained symptoms, are described.


Guiding locomotion in complex, dynamic environments.
Locomotion in complex, dynamic environments is an integral part of many daily activities, including walking in crowded spaces, driving on busy roadways, and playing sports. Many of the tasks that humans perform in such environments involve interactions with moving objects-that is, they require people to coordinate their own movement with the movements of other objects. A widely adopted framework for research on the detection, avoidance, and interception of moving objects is the bearing angle model, according to which observers move so as to keep the bearing angle of the object constant for interception and varying for obstacle avoidance. The bearing angle model offers a simple, parsimonious account of visual control but has several significant limitations and does not easily scale up to more complex tasks. In this paper, I introduce an alternative account of how humans choose actions and guide locomotion in the presence of moving objects. I show how the new approach addresses the limitations of the bearing angle model and accounts for a variety of behaviors involving moving objects, including (1) choosing whether to pass in front of or behind a moving obstacle, (2) perceiving whether a gap between a pair of moving obstacles is passable, (3) avoiding a collision while passing through single or multiple lanes of traffic, (4) coordinating speed and direction of locomotion during interception, (5) simultaneously intercepting a moving target while avoiding a stationary or moving obstacle, and (6) knowing whether to abandon the chase of a moving target. I also summarize data from recent studies that support the new approach.


Overview of executive order 13148: requirements for environmental management systems at federal facilities.
In April 2000, the White House issued Executive Order 13148, Greening the Government Through Leadership in Environmental Management. This Order applies to all appropriate federal facilities that have operations which interact with the environment and includes a number of environmentally-related requirements. The most significant requirement is that all appropriate federal facilities must implement an Environmental Management System (EMS) by December 31, 2005. This Order affects federal laboratories, testing facilities, maintenance facilities, hospitals, and so forth across all federal departments and agencies.


Optimization of bacteriocin ST311LD production by Enterococcus faecium ST311LD, isolated from spoiled black olives.
Bacteriocin ST311LD is approximately 2.3 kDa in size. Low levels of bacteriocin activity were recorded in BHI and M17 broth (800 AU/ml) and in 10% (w/v) soy milk (3,200 AU/ml). No bacteriocin production was recorded in 10% (w/v) molasses, despite good growth. Optimal levels (12,800 AU/ml) were detected in MRS broth which had been supplemented with tryptone (20.0 g/l), saccharose (5.0 or 10.0 g/l) or vitamin C (1 ppm). Increased potassium levels did not result in higher levels of activity, and glycerol (1.0 g/l) inhibited the production of bacteriocin ST311LD.


Kinetic analysis of tubulin assembly in the presence of the microtubule-associated protein TOGp.
The microtubule-associated protein TOGp, which belongs to a widely distributed protein family from yeasts to humans, is highly expressed in human tumors and brain tissue. From purified components we have determined the effect of TOGp on thermally induced tubulin association in vitro in the presence of 1 mm GTP and 3.4 m glycerol. Physicochemical parameters describing the mechanism of tubulin polymerization were deduced from the kinetic curves by application of the classical theoretical models of tubulin assembly. We have calculated from the polymerization time curves a range of parameters characteristic of nucleation, elongation, or steady state phase. In addition, the tubulin subunits turnover at microtubule ends was deduced from tubulin GTPase activity. For comparison, parallel experiments were conducted with colchicine and taxol, two drugs active on microtubules and with tau, a structural microtubule-associated protein from brain tissue. TOGp, which decreases the nucleus size and the tenth time of the reaction (the time required to produce 10% of the final amount of polymer), shortens the nucleation phase of microtubule assembly. In addition, TOGp favors microtubule formation by increasing the apparent first order rate constant of elongation. Moreover, TOGp increases the total amount of polymer by decreasing the tubulin critical concentration and by inhibiting depolymerization during the steady state of the reaction.


Distributed Fiber Optics Sensing and Coda Wave Interferometry Techniques for Damage Monitoring in Concrete Structures.
The assessment of Coda Wave Interferometry (CWI) and Distributed Fiber Optics Sensing (DFOS) techniques for the detection of damages in a laboratory size reinforced concrete beam is presented in this paper. The sensitivity of these two novel techniques to micro cracks is discussed and compared to standard traditional sensors. Moreover, the capacity of a DFOS technique to localize cracks and quantify crack openings is also assessed. The results show that the implementation of CWI and DFOS techniques allow the detection of early subtle changes in reinforced concrete structures until crack formation. With their ability to quantify the crack opening, following early detection and localization, DFOS techniques can achieve more effective monitoring of reinforced concrete structures. Contrary to discrete sensors, CWI and DFOS techniques cover larger areas and thus provide more efficient infrastructures asset management and maintenance operations throughout the lifetime of the structure.


Outcomes of lung transplant recipients with preoperative atrial fibrillation.
Background Preoperative atrial fibrillation is associated with poor outcomes after cardiac surgery, but its effect on lung transplantation outcomes remains unknown. Methods We retrospectively reviewed the charts of 235 patients who underwent lung transplantation in our institution from 2013 to 2015, analyzing demographics, length of stay, survival, readmissions, and cardiac events. Mean recipient age was 59 ± 11 years, and 142 (60.4%) were men. Patients were grouped according to pre-transplantation atrial fibrillation status (atrial fibrillation/no atrial fibrillation). Results The atrial fibrillation group ( n = 38; 16.2%) was significantly older with a longer ischemic time, more postoperative atrial arrhythmias (73.7% vs. 20.8%, p = 0.01), and a longer median postoperative length of stay (16 vs. 13 days, p = 0.02). The median total hospital stay in the first postoperative year was also higher in the atrial fibrillation group (27 vs. 21 days, p = 0.25). Short-term survival and survival during follow-up did not differ significantly between groups. Conclusions Lung transplant recipients with preoperative atrial fibrillation are at increased risk of adverse cardiovascular outcomes and longer hospital stay. Preoperative atrial fibrillation may portend adverse events after lung transplantation.


Two new naphthalene and anthraquinone derivatives from Asphodelus tenuifolius.
Chromatographic separation of an ethanolic extract of rhizomes of Asphodelus tenuifolius Cav. (Asphodelaceae) yielded in addition to beta-sitosterol, stigmasterol and two anthraquinone derivatives, 1,8-dimethoxynaphthalene as well as two new naphthalene derivatives. The new compounds were identified as 2-acetyl-8-methoxy-3-methyl-1-naphthol and 2-acetyl-1,8-dimethoxy-3-methylnaphthalene. The separated compounds were identified on the basis of IR, MS, 1H and 13C NMR data.


Surgical Anatomy of the Superior Mesenteric Vessels Related to Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis.
Mesopancreas dissection with central vascular ligation and the superior mesenteric artery (SMA)-first approach represent the cornerstone of current principles for radical resection for pancreatic head cancer. The surgeon dissecting around the SMV and SMA should be aware regarding the anatomical variants in this area. The aims of this systematic review and meta-analysis are to detail the surgical anatomy of the superior mesenteric vessels and to propose a standardized terminology with impact in pancreatic cancer surgery. We conducted a systematic search to identify all published studies in PubMed/MEDLINE and Google Scholar databases from their inception up to March 2017. Seventy-eight studies, involving a total of 18,369 specimens, were included. The prevalence of the mesenteric-celiac trunk, replaced/accessory right hepatic artery (RRHA), common hepatic artery, and SMV inversion was 2.8, 13.2, 2.6, and 4.1%, respectively. The inferior pancreaticoduodenal artery has its origin into the first jejunal artery, SMA, and RRHA, in 58.7, 35.8, and 1.2% of cases, respectively. The SMV lacks a common trunk in 7.5% of cases. The first jejunal vein has a trajectory posterior to the SMA in 71.8% of cases. The left gastric vein drains into the portal vein in 58%, in splenic vein (SV) in 35.6%, and into the SV-PV confluence in 5.8% of cases. Complex pancreaticoduodenal resections require detailed knowledge of the superior mesenteric artery and vein, which is significantly different from the one presented in the classical textbooks of surgery. We are proposing the concept of the first jejunopancreatic vein which impacts the current oncological principles of pancreatic head cancer resection.


In silico computational drug discovery: a Monte Carlo approach for developing a novel JAK3 inhibitors.
Inhibition of Janus kinase 3 (JAK3), a member of the JAK family of tyrosine kinases, remains an essential area of research for developing treatments for autoimmune diseases, particularly cancer and rheumatoid arthritis. The recent discovery of a new JAK3 protein, PDB ID: 4Z16, offers exciting possibilities for developing inhibitors capable of forming a covalent bond with the Cys909 residue, thereby contributing to JAK3 inhibition. A powerful prediction model was constructed and validated using Monte Carlo methods, employing various internal and external techniques. This approach resulted in the prediction of eleven new molecules, which were subsequently filtered to identify six compounds exhibiting potent pIC50 values. These candidates were then subjected to ADMET analysis, molecular docking (including reversible-reversible docking with tofacitinib, an FDA-approved drug, and reversible-irreversible docking for the newly designed compounds), molecular dynamics (MD) analysis for 300 ns, and calculation of free binding energy. The results suggested that these compounds hold promise as JAK3 inhibitors. In summary, the new compounds have exhibited favorable outcomes compared to other compounds across various modeling approaches. The collective findings from these investigations provide valuable insights into the potential therapeutic applications of covalent JAK3 inhibitors, offering a promising direction for the development of novel treatments for autoimmune disorders.Communicated by Ramaswamy H. Sarma.


Inflammation and oxidative stress in patients on hemodiafiltration.
Chronic inflammation and oxidative stress are common features in hemodialysis patients. However, research results on the long-term influence of hemodiafiltration (HDF) on oxidative stress and inflammation are limited. We studied changes of inflammatory and oxidative stress biomarkers in 9 stable patients on post-dilution HDF for 9 months. Total antioxidant capacity (TAC), reactive oxygen metabolites (d-ROMs) and superoxide dismutase (SOD) measured by spectrophotometry were used as oxidative stress biomarkers. High-sensitivity CRP (hs-CRP) and IL-6 measured by ELISA were used as inflammation biomarkers. d-ROMs showed significant reduction at 3 months (323.0 +/- 81.9 vs. 275.0 +/- 62.0 U, p < 0.008) and remained low (267.9 +/- 45.8 U) to the end of the study. At the end of the study there was a significant increase in TAC levels (1.3 +/- 0.1 vs. 1.4 +/- 0.1 mmol/l, p < 0.03), while SOD rise did not reach statistical significance (13.1 +/- 9.8 vs. 18.7 +/- 9.4 U/ml, p = 0.06). hs-CRP values at the end of the study decreased significantly (16.3 +/- 11.4 vs. 6.0 +/- 5.1 microg/ml, p < 0.02), while IL-6 levels showed a non-significant reduction (16.9 +/- 9.3 vs. 12.0 +/- 7.3 pg/ml, p = 0.2). Our results suggest that post-dilution HDF for 9 months suppresses oxidative stress by rapid lowering of d-ROMs and improves antioxidant capacity by increasing TAC, while it reduces inflammation by decreasing hs-CRP.


On being a whistleblower: the Needleman case.
We believe that members of the scientific community have a primary obligation to promote integrity in research and that this obligation includes a duty to report observations that suggest misconduct to agencies that are empowered to examine and evaluate such evidence. Consonant with this responsibility, we became whistleblowers in the case of Herbert Needleman. His 1979 study (Needleman et al., 1979), on the effects of low-level lead exposure on children, is widely cited and highly influential in the formulation of public policy on lead. The opportunity we had to examine subject selection and data analyses from this study was prematurely halted by efforts to prevent disclosure of our observations. Nevertheless, what we saw left us with serious concerns. We hope that the events here summarized will contribute to revisions of process by which allegations of scientific misconduct are handled and that such revisions will result in less damage to scientists who speak out.


Surface heparinization and blood compatibility modification of small intestinal submucosa (SIS) for small-caliber vascular regeneration.
This study aims to investigate the small intestinal submucosal (SIS) surface after heparinization with the hypothermia plasma technique, to improve the blood compatibility of SIS, and to explore the possibility of construction of small-caliber vascular grafts with modified SIS scaffolds in vivo. SIS films prepared from jejunums of pigs were processed for surface treatment at different time periods with the argon plasma initiation technique under vacuum, and were then immediately immersed in 4% (m/v) heparin sodium solution for 24-h heparinization. The surface morphologies of heparinized SIS were observed under a scanning electron microscope (SEM). The antithrombogenicity of the modified SIS films was tested by measuring the water contact angle, blood coagulation time, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and observation of platelet adherence by SEM. Heparinized SIS films were sewn into a small caliber (3-mm) tube and implanted into the defect of a canine femur by anastomosis as a vascular graft. The efficiency of the SIS graft was evaluated according to the patency for the circulation of blood with Doppler color ultrasonography and hematoxylin-eosin staining. Heparinized SIS showed a significantly different surface morphology compared with that of untreated SIS. The SIS surface resembles wrinkled film, but the heparinized SIS surface is uniformly coated with microdots, and appears to have a layer of heparin adhesion. Heparin was attached to the SIS surface after hypothermia plasma treatment. Hydrophilicity and antithrombogenicity of heparinized SIS were clearly increased. The heparinized SIS vascular graft showed great potential for replacement of defective small-caliber vessels.


[Immediate reconstruction of the breast following mastectomy].
Immediate reconstruction of the breast has become an integral part of treatment of breast cancer during the last years. Several studies have reported that breast cancer patients who undergo immediate reconstruction have the same survival rates as unreconstructed patients and that reconstruction does not adversely affect the natural course of breast cancer. Since 1983 immediate reconstruction has been performed in 87 patients at our institution. It has been demonstrated that the psychological trauma has been dramatically reduced and that many patients will accept mastectomy almost with a sense of relief, when immediate reconstruction can be offered.


A randomized, double-blind, placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome.
Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.


Changes in the soundscape of Girona during the COVID lockdown.
The lockdown measures in Spain due to COVID-19 social measures showed a wide decrease in the urban noise levels observed. This paper presents an analysis of the noise levels in Girona, a 100 000 citizen city in the North-East of Catalonia (Spain). We present the LAeq levels in four different locations from January 2020 to June 2020, including all the stages of the lockdown. Several comparisons are conducted with the monitoring data available from the previous years (2019, 2018, and 2017, when available). This analysis is part of the project "Sons al Balcó," which aims to draw the soundscape of Catalonia during the lockdown. The results of the analysis in Girona show drastic LAeq changes especially in nightlife areas of the city, moderate LAeq changes in commercial and restaurants areas, and low LAeq changes in dense traffic areas.


Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Analysis of Fluconazole, Isavuconazole, Itraconazole, Hydroxy-Itraconazole, Posaconazole, and Voriconazole in Human Plasma and Serum.
A fast and easy-to-use liquid chromatography-tandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed and validated for therapeutic drug monitoring. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. Isotope-labeled analogues for each analyte were used as internal standards. Chromatographic separation was achieved using a 50 × 2.1 mm, 1.9 μm polar Hypersil Gold C18 column and mobile phase consisting of 0.1% formic acid/acetonitrile (45%/55%, vol/vol) at a flow rate of 340 μL/min. The triazoles were simultaneously detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring mode with positive heated electrospray ionization within a single runtime of t = 3.00 minutes. Linearity of all azole concentration ranges was verified by the Mandel test and demonstrated for all azoles. All calibration curves were linear and fitted using least squares regression with a weighting factor of the reciprocal concentration. Limits of detection (μg/L/L) were FLZ, 9.3; ISZ, 0.3; ITZ, 0.6; OH-ITZ, 8.6; PSZ, 3.4; and VRZ, 2.1. The lower limits of quantitation (μg/L/liter) were FLZ, 28.3; ISZ, 1.0; ITZ, 1.7; OH-ITZ, 26.2; PSZ, 10.3; and VRZ, 6.3. Intraday and interday precisions ranged from 0.6% to 6.6% for all azoles. Intraday and interday accuracies (%bias) of all analytes were within 10.5%. In addition, we report on a 29-year-old white woman (94 kg body weight) with a history of acute myeloid leukemia who underwent stem cell transplantation. Because of diagnosis of aspergillus pneumonia, antifungal pharmacotherapy was initiated with different application modes and dosages of ISZ, and plasma concentrations were monitored over a time period of 6 months. A precise and highly sensitive liquid chromatography-tandem mass spectrometry method was developed that enables quantification of triazoles in plasma and serum matrix across therapeutically relevant concentration ranges. It was successfully implemented in our therapeutic drug monitoring routine service and is suitable for routine monitoring of antifungal therapy and in severely ill patients.


Optimizing penile length in patients undergoing partial penectomy for penile cancer: novel application of the ventral phalloplasty oncoplastic technique.
The ventral phalloplasty (VP) has been well described in modern day penile prosthesis surgery. The main objectives of this maneuver are to increase perceived length and patient satisfaction and to counteract the natural 1-2 cm average loss in length when performing implantation of an inflatable penile prosthesis. Similarly, this video represents a new adaptation for partial penectomy patients. One can only hope that the addition of the VP for partial penectomy patients with good erectile function will increase their quality of life. The patient in this video is a 56-year-old male who presented with a 4.0x3.5x1.0 cm, pathologic stage T2 squamous cell carcinoma of the glans penis. After partial penectomy with VP and inguinal lymph node dissection, pathological specimen revealed negative margins, 3/5 right superficial nodes and 1/5 left superficial nodes positive for malignancy. The patient has been recommended post-operative systemic chemotherapy (with external beam radiotherapy) based on the multiple node positivity and presence of extranodal extension. The patient's pre-operative penile length was 9.5 cm, and after partial penectomy with VP, penile length is 7 cm.


Immunofluorescent staining for collagen and proteoglycan in normal and scoliotic intervertebral discs.
Specific antisera to collagen Types I, II and III and proteoglycan were used to investigate the distributions of these molecules in normal human intervertebral discs. Immunofluorescent staining indicated the presence of small amounts of Type III collagen located pericellularly in normal adult intervertebral discs. This finding had not been demonstrated previously by other methods. Similar specimens of intervertebral discs from 17 patients with scoliosis of varying aetiologies were examined, but no evidence was obtained for primary connective tissue defects. Secondary changes, especially marked vascularisation of the inner annulus, were apparent in a number of scoliotic discs, and some of these showed enhanced staining for collagen Type I and proteoglycan, and intercellular matrix staining for Type III collagen.


Dicarbollylamine ligand as a tunable template for sigma,sigma- and pi,sigma-bonding modes: syntheses, structures, and theoretical studies of eta5:eta1-coordinated constrained-geometry group 13 metal complexes.
A series of group 13 main group complexes with pi,sigma-type bonding interaction of the formula [{(eta (5)-RC 2B 9H 9)(CH 2)(eta (1)-NMe 2)}MMe] (M = Al, R = H 5, Me 6; Ga, R = H 7, Me 8; In, R = H 9, Me 10) was produced by the reaction of group 13 metal alkyls (MMe 3; M = Al, Ga, In) with the dicarbollylamine ligands, nido-8-R-7,8-C 2B 9H 10-7-(CH 2)NHMe 2 (R = H 1, Me 2). The reactions of 1 and 2 with AlMe 3 in toluene initially afforded tetra-coordinated aluminum complexes with sigma,sigma-type bonding interaction, [{(eta (1)-RC 2B 9H 10)(CH 2)(eta (1)-NMe 2)}AlMe 2] (R = H 3, Me 4), which readily underwent further methane elimination to yield the corresponding constrained geometry complexes (CGCs, 5 and 6) of aluminum with pi,sigma-bonding interaction. However, the reactions between 1 and 2 and MMe 3 (M = Ga, In) in toluene produced gallium and indium pi,sigma-CGCs of 7 and 10 directly, not proceeding through sigma,sigma-intermediates. The structures of group 13 metal CGCs were established by X-ray diffraction studies of 5, 6, and 8, which authenticated a characteristic eta (5):eta (1)-coordination mode of the dicarbollylamino ligand to the group 13 metals. A similar pi,sigma-bonding interaction was also established in ethylene-bridged dicarbollylethylamine series. Thus, aluminum pi,sigma-CGCs of dicarbollylethylamine, [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}AlMe] (R = H 17, Me 18), were prepared by the trans-metalation of the [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}Ti(NMe 2) 2] (R = H 15, Me 16) with AlMe 3. However, only sigma,sigma-bonded complexes of the formula [{(eta (1)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}AlMe 2] (R = H 13, Me 14) were isolated by the reaction between [ nido-7-8-R-7,8-C 2B 9H 10-(CH 2) 2HNBz 2] (R = H 11, Me 12) and AlMe 3. When methane-elimination reactions between metal alkyls and dicarbollylamines were carried out with either the gallium atom or monobenzyl aminoethyl tethered ligands, [ nido-7-H 2NBz(CH 2) 2-8-R-7,8-C 2B 9H 10] (R = H 21, Me 22), desired pi,sigma-CGCs, [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}GaMe] (R = H 19, Me 20) or [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NHBz)}AlMe] (R = H 23, Me 24), were generated, respectively. DFT calculation on 5 provides evidence of existence of pi,sigma-bonding of dicarbollylamine ligand to the aluminum atom: pi-bonding interaction of a dicarbollyl unit becomes intensified in the presence of a weak sigma-bonding amine-tethered group. Furthermore, preference for the formation of pi,sigma-bonding was predicted by optimizing a reaction profile including sigma,sigma- and pi,sigma-structures as well as transition state structures for each methylene- and ethylene-spaced ligand system, 3-5 and 14- 18, to reveal that pi,sigma-bonding interaction is more favorable in the case of a methylene-tethered ligand system.


Massive pericardial effusion and dilated cardiomyopathy in a patient with familial multiple myeloma.
An 80-years-old-man with adult polycystic kidney disease and familial multiple myeloma that is complicated with massive pericardial effusion and dilated cardiomyopathy during the course of the disease is presented. Although no definite single genetic disorder is described, multiple myeloma cases may be seen in certain families. Environmental factors are also blamed in the etiology. Multiple myeloma may be complicated by myocardial and pericardial involvement, diagnoses of which are possible only during postmortem examination in some cases.


Ecosystem service trade-offs and their influencing factors: A case study in the Loess Plateau of China.
Soil erosion control (SEC), carbon sequestration (CAS), and soil moisture (SMO) strongly interact in the semi-arid Loess Plateau. Since SMO has supportive effects on SEC and CAS, it can be considered as ecosystem service (ES), and there is an immediate need to coordinate the relationships among these ecosystem services (ESs) to promote the sustainability of vegetation recovery. In this study, we quantified the ESs, ES trade-offs, and the environmental factors in 151 sample plots in the Ansai watershed, and we used a redundancy analysis (RDA) to clarify the effects of environmental factors on these ESs and their trade-offs. The results were as follows: (1) the general trend in the SEC of vegetation types was Robinia pseudoacacia (CH)>native grass (NG)>small arbor (ST)>Hippophae rhamnoides (SJ)>artificial grass (AG)>Caragana korshinskii (NT)>apple orchard (GY)>crop (CP); the CAS trend was CH>SJ>NT>AG>CP>ST>GY>NG; and the SMO trend was CP>NG>GY>AG>SJ>ST>CH>NT. (2) For SEC-SMO trade-offs, the influence of vegetation type, altitude, silt and sand composition was dominant. The arrangement of NG, AG, and SJ could decrease the extent of the trade-offs. (3) For CAS-SMO trade-offs, vegetation coverage and types were the dominant factors, but the effects were not complex. The extent of these trade-offs was lowest for NT, and that for SJ was the second lowest. (4) Considering the relationships among the three ESs, SJ was the most appropriate afforestation plant. Combing the vegetation types, slope position, slope gradient, and soil properties could regulate these ES relationships. The dominant factors influencing ES trade-offs varied among the different soil layers, so we must consider the corresponding influencing factors to regulate ESs. Moreover, manual management measures were also important for coordinating the ES relationships. Our research provides a better understanding of the mechanisms influencing the relationships among ESs.


Mechanistic Insight from Calorimetric Measurements of the Assembly of the Binuclear Metal Active Site of Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes.
Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a binuclear metallohydrolase with a high affinity for metal ions at its α site but a lower affinity at its β site in the absence of a substrate. Isothermal titration calorimetry (ITC) has been used to quantify the Co(II) and Mn(II) binding affinities and thermodynamics of the two sites in wild-type GpdQ and two mutants, both in the absence and in the presence of phosphate. Metal ions bind to the six-coordinate α site in an entropically driven process with loss of a proton, while binding at the β site is not detected by ITC. Phosphate enhances the metal affinity of the α site by increasing the binding entropy and the metal affinity of the β site by enthalpic (Co) or entropic (Mn) contributions, but no additional loss of protons. Mutations of first- and second-coordination sphere residues at the β site increase the metal affinity of both sites by enhancing the binding enthalpy. In particular, loss of the hydrogen bond from second-sphere Ser127 to the metal-coordinating Asn80 has a significant effect on the metal binding thermodynamics that result in a resting binuclear active site with high catalytic activity. While structural and spectroscopic data with excess metal ions have indicated a bridging hydroxide in the binuclear GpdQ site, analysis of ITC data here reveals the loss of a single proton in the assembly of this site, indicating that the metal-bound hydroxide nucleophile is formed in the resting inactive mononuclear form, which becomes catalytically competent upon binding the second metal ion.


Sensing Biomarkers with Plasmonics.
The detection of biomarkers is critical for enabling early disease diagnosis, monitoring the progression, and tracking the effectiveness of therapeutic intervention. Plasmonic sensors exhibit a broad range of analytical capabilities, from the rapid generation of colorimetric readouts to single-molecule sensitivity in ultralow sample volumes, which have led to their increased exploration in bioanalysis and point-of-care applications. This perspective presents selected accounts of recent developments on the different types of plasmonic sensing platforms, the pervasive challenges, and outlook on the pathway to translation. We highlight the sensing of upcoming biomarkers, including microRNA, circulating tumor cells, exosomes, and cell-free DNA, and discuss the opportunity of utilizing plasmonic nanomaterials and tools for biomarker detection beyond biofluids, such as in tissues, organs, and disease sites. The integration of plasmonic biosensors with established and upcoming technologies of instrumentation, sample pretreatment, and data analysis will help realize their translation to clinical settings for improving healthcare and enhancing the quality of life.


Correction: Separately doped upconversion-C60 nanoplatform for NIR imaging-guided photodynamic therapy of cancer cells.
Correction for 'Separately doped upconversion-C60 nanoplatform for NIR imaging-guided photodynamic therapy of cancer cells' by Xiaomin Liu et al., Chem. Commun., 2013, 49, 3224-3226.


N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.
Gestational trophoblastic neoplasia (GTN) results from the malignant transformation of placental trophoblasts which secrete human chorionic gonadotropin (hCG) as do normal placenta or hydatidiform mole. N-acetylglucosaminyltransferase IV (GnT-IV) is a glycosyltransferase which catalyses the formation of β1,4GlcNAc branches on the mannose core of N-glycans. Previous studies reported that β1,4GlcNAc branches on hCG were detected in GTN but not in normal pregnancy or hydatidiform mole. The aim of the present study was to understand the role of GnT-IVa in choriocarcinoma and find the target proteins for GnT-IVa glycosylation which contribute to the malignancy of choriocarcinoma. Immunohistochemistry showed that Griffonia simplicifolia lectin-II staining and GnT-IVa staining were intense in trophoblastic cells of invasive mole and choriocarcinoma. We established a choriocarcinoma cell line with GnT-IVa overexpression (Jar-GnT4a), and examined its malignant potential and target proteins for GnT-IVa glycosylation. GnT-IVa overexpression increased the cell migration and invasion (2.5- and 1.4-fold) as well as the ability to adhere to the extracellular matrix (ECM) components, including fibronectin and collagen type I and IV. The tumour formation potential of Jar-GnT4a in mice was significantly higher than that of control (P=0.0407), and the cumulative survival rate of mice with Jar-GnT4a was relatively lower than those with control. Immunoprecipitation studies showed that β1,4GlcNAc branches of N-glycans on integrin β1 in choriocarcinoma cells were increased by GnT-IVa overexpression. Nano-LC/MS/MS analysis suggested that lysosome-associated membrane glycoprotein 2 (LAMP-2) was a target protein for glycosylation by GnT-IVa. The increase in β1,4GlcNAc branches on LAMP-2 by GnT-IVa overexpression was confirmed by lectin blot analysis using whole cell lysate and conditioned medium. Our results suggest that highly branched N-glycans generated by the action of GnT-IVa are present in trophoblastic cells of GTN in proportion to GnT-IVa expression level, and that GnT-IVa may contribute to the malignancy of choriocarcinoma by promoting cell adhesion, migration and invasion through glycosylation of integrin β1 and LAMP-2.


Defined extracellular matrix compositions support stiffness-insensitive cell spreading and adhesion signaling.
Integrin-dependent adhesion to the extracellular matrix (ECM) mediates mechanosensing and signaling in response to altered microenvironmental conditions. In order to provide tissue- and organ-specific cues, the ECM is composed of many different proteins that temper the mechanical properties and provide the necessary structural diversity. Despite most human tissues being soft, the prevailing view from predominantly in vitro studies is that increased stiffness triggers effective cell spreading and activation of mechanosensitive signaling pathways. To address the functional coupling of ECM composition and matrix rigidity on compliant substrates, we developed a matrix spot array system to screen cell phenotypes against different ECM mixtures on defined substrate stiffnesses at high resolution. We applied this system to both cancer and normal cells and surprisingly identified ECM mixtures that support stiffness-insensitive cell spreading on soft substrates. Employing the motor-clutch model to simulate cell adhesion on biochemically distinct soft substrates, with varying numbers of available ECM-integrin-cytoskeleton (clutch) connections, we identified conditions in which spreading would be supported on soft matrices. Combining simulations and experiments, we show that cell spreading on soft is supported by increased clutch engagement on specific ECM mixtures and even augmented by the partial inhibition of actomyosin contractility. Thus, "stiff-like" spreading on soft is determined by a balance of a cell's contractile and adhesive machinery. This provides a fundamental perspective for in vitro mechanobiology studies, identifying a mechanism through which cells spread, function, and signal effectively on soft substrates.


Training Spiking Neural Networks for Cognitive Tasks: A Versatile Framework Compatible With Various Temporal Codes.
Recent studies have demonstrated the effectiveness of supervised learning in spiking neural networks (SNNs). A trainable SNN provides a valuable tool not only for engineering applications but also for theoretical neuroscience studies. Here, we propose a modified SpikeProp learning algorithm, which ensures better learning stability for SNNs and provides more diverse network structures and coding schemes. Specifically, we designed a spike gradient threshold rule to solve the well-known gradient exploding problem in SNN training. In addition, regulation rules on firing rates and connection weights are proposed to control the network activity during training. Based on these rules, biologically realistic features such as lateral connections, complex synaptic dynamics, and sparse activities are included in the network to facilitate neural computation. We demonstrate the versatility of this framework by implementing three well-known temporal codes for different types of cognitive tasks, namely, handwritten digit recognition, spatial coordinate transformation, and motor sequence generation. Several important features observed in experimental studies, such as selective activity, excitatory-inhibitory balance, and weak pairwise correlation, emerged in the trained model. This agreement between experimental and computational results further confirmed the importance of these features in neural function. This work provides a new framework, in which various neural behaviors can be modeled and the underlying computational mechanisms can be studied.


Elimination of para-aminosalicylic acid in patients with liver disease and renal insufficiency.
The elimination of para-aminosalicylic acid (PAS) after the intravenous injection of 20 mg PAS sodium/kg was estimated in patients with liver disease, in uremic patients and in volunteers without damage of the liver or kidneys. The drug was estimated with a colorimetric and fluorometric method. In the volunteers, the half-lives obtained with the fluorometric method were significantly longer than those estimated with the colorimetric method. This is caused by the estimation of more PAS metabolites by the used fluorometric method. In the patients with renal insufficiency (dialysis patients) the elimination rate of unchanged PAS--estimated with the colorimetric method--was not altered, whereas the elimination of PAS and its metabolites extractable by ethyl acetate was markedly slowed in comparison with the results obtained with the volunteers. The clearance of the unchanged PAS was even increased in the uremic patients. The serum protein binding of PAS was lowered significantly in the serum of uremic patients. In patients with liver cirrhosis, acute virus hepatitis and cholangitis the elimination rate of the drug was not altered in comparison with the volunteers. The results show that the dose of PAS in patients with renal insufficiency may not be reduced. The therapeutic level of the drug cannot otherwise be reached in these patients.


The influence of amino substitutions within the mature part of an Escherichia coli outer membrane protein (OmpA) on assembly of the polypeptide into its membrane.
The membrane part of the 325-residue outer membrane protein OmpA of Escherichia coli encompasses residues 1-177. This part is thought to cross the membrane eight times in antiparallel beta-strands, forming four loops of an amphipathic beta-barrel. With the aim of gaining some insight into the mechanism of sorting, i.e. the way the protein recognizes and assembles into its membrane, a set of point mutants in the ompA gene has been generated. Selection for toxicity of ompA expression following mutagenesis with sodium bisulfite yielded genes with multiple base pair substitutions, the majority of which resulted in amino acid substitutions in the membrane moiety of the protein. None of the altered proteins was blocked in membrane incorporation. A proline residue exists at or near each of the presumed turns at the inner side of the outer membrane. Using oligonucleotide-directed mutagenesis, each of them was replaced by a leucine residue which is thought to be a turn blocking residue. None of these proteins had lost the ability to be incorporated into the membrane. Apparently, leucine residues are tolerated at turns in this protein. To interfere with the formation of antiparallel beta-strands, four double mutants were prepared: ompA-ON3 (Ala11----Pro, Leu13----Pro), -ON4 (Ala11----Asp, Leu13----Pro), -ON5 (Gly160----Val, Leu162----Arg), and -ON6 (Leu164----Pro, Val166----Asp). The former three proteins and even quadruple mutants consisting of a combination of ompA-ON2 or -ON4 with -ON5 were not defective in membrane assembly. In contrast, the OmpA-ON6 protein was translocated across the plasma membrane but could not be incorporated into the outer membrane. It is concluded that at least one rather small area of the polypeptide is of crucial importance for the assembly of OmpA into the outer membrane.


Acoustic holography as a metrological tool for characterizing medical ultrasound sources and fields.
Acoustic holography is a powerful technique for characterizing ultrasound sources and the fields they radiate, with the ability to quantify source vibrations and reduce the number of required measurements. These capabilities are increasingly appealing for meeting measurement standards in medical ultrasound; however, associated uncertainties have not been investigated systematically. Here errors associated with holographic representations of a linear, continuous-wave ultrasound field are studied. To facilitate the analysis, error metrics are defined explicitly, and a detailed description of a holography formulation based on the Rayleigh integral is provided. Errors are evaluated both for simulations of a typical therapeutic ultrasound source and for physical experiments with three different ultrasound sources. Simulated experiments explore sampling errors introduced by the use of a finite number of measurements, geometric uncertainties in the actual positions of acquired measurements, and uncertainties in the properties of the propagation medium. Results demonstrate the theoretical feasibility of keeping errors less than about 1%. Typical errors in physical experiments were somewhat larger, on the order of a few percent; comparison with simulations provides specific guidelines for improving the experimental implementation to reduce these errors. Overall, results suggest that holography can be implemented successfully as a metrological tool with small, quantifiable errors.


[Effects of surgery on muscles on clinical and radiographic findings in the hip joint region in cerebral palsy patients].
PURPOSE OF THE STUDY Isolated or combined surgical procedures on muscles around the hip joint are currently indicated by many authors. In cerebral palsy patients they are regarded as essential intervention. MATERIAL In the years 2005-2007, surgery in the hip joint region was essential for 150 children between 3 and 18 years of age. At the time of surgery, the patients' locomotion ranged from stage 1 to stage 7 of the Vojta system. METHODS The outcome was evaluated by clinical and radiographic examination at 2 and 6 months post-operatively and hip migration percentage and Wiberg's CE angle were measured. RESULTS The best clinical and radiographic outcomes were achieved in children younger than 6 years of age. On the other hand, isolated transfer of the distal rectus femoris muscle significantly affected pelvis anteflexion in adolescent patients. The most marked decrease in migration percentage was found after adductor tenotomy combined with surgery on the iliopsoas muscle (55.6 %) or when the two procedures were combined with distal rectus femoris transfer. DISCUSSION Combined surigical procedures, i.e., adductor tenotomy, surgery on the iliopsoas muscle or rectus femoris muscle and medial hamstrings, with fixation using an abduction modified Atlanta brace, are effective in patients with marked lateral hip migration who are younger that 6 years. Isolated adductor tenotomy and distal transfer of the rectus femoris muscle markedly improve standing position in walking patients. CONCLUSION An appropriate combination of surgical procedures on muscles in the hip region and on medial hamstrings can significantly improve the patient's locomotion and, if lateral migration is present, help to avoid surgery on bones.


Non-antibiotic 12-membered macrolides: design, synthesis and biological evaluation in a cigarette-smoking model.
The 14-membered macrolide erythromycin A expresses three distinct biological properties, including antibacterial activity, gastrointestinal motor-stimulating activity and anti-inflammatory and/or immunomodulatory effects. Although low-dose, long-term therapy using 14- and 15-membered macrolides displaying anti-inflammatory and/or immunomodulatory activity effectively treats diffuse panbronchiolitis and chronic sinusitis, bacterial resistance may emerge. To address this issue, we developed the 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900) that promotes monocyte to macrophage differentiation, a marker for anti-inflammatory and/or immunomodulatory effects, without possessing antibacterial activity. In this article, we report that the new macrolide derivative (8R,9S) -de(3'-N-methyl)-3'-N-(p-chlorobenzyl)-de(3-O-cladinosyl)-3-dehydro-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A 12,13-carbonate (EM939) exhibited stronger promotive activity for monocyte to macrophage differentiation than that of the parent compound EM900 in addition to reduced cytotoxicity toward THP-1 cells and antibacterial inactivity. In a cigarette-smoking model used to simulate chronic obstructive pulmonary disease (COPD), the EM900 derivatives significantly attenuated lung and alveolar inflations, functionally and histologically, via oral administration. Because of these marked therapeutic effects, non-antibiotic EM900 derivatives may become central to the treatment of chronic inflammatory diseases such as COPD.


Estimating generation time of SARS-CoV-2 variants in Italy from the daily incidence rate.
The identification of the transmission parameters of a virus is fundamental to identify the optimal public health strategy. These parameters can present significant changes over time caused by genetic mutations or viral recombination, making their continuous monitoring fundamental. Here we present a method, suitable for this task, which uses as unique information the daily number of reported cases. The method is based on a time since infection model where transmission parameters are obtained by means of an efficient maximization procedure of the likelihood. Applying the method to SARS-CoV-2 data in Italy, we find an average generation time [Formula: see text] days, during the temporal window when the majority of infections can be attributed to the Omicron variants. At the same time we find a significantly larger value [Formula: see text] days, in the temporal window when spreading was dominated by the Delta variant. We are also able to show that the presence of the Omicron variant, characterized by a shorter [Formula: see text], was already detectable in the first weeks of December 2021, in full agreement with results provided by sequences of SARS-CoV-2 genomes reported in national databases. Our results therefore show that the novel approach can indicate the existence of virus variants, resulting particularly useful in situations when information about genomic sequencing is not yet available. At the same time, we find that the standard deviation of the generation time does not significantly change among variants.


Rational primer design greatly improves differential display-PCR (DD-PCR).
Since its conception in 1992, differential display PCR (DD-PCR) has attracted widespread interest. Theoretically an attractive cloning approach, it combines the comparative analysis of several samples with the sensitivity of PCR. Although a large number of studies embracing this technology have been initiated, few novel genes of interest have been identified, suggesting that the method has not realised its potential. The present report shows that by modifying primer design, sampling of differentially expressed genes can be greatly enhanced and relevant genes can be isolated. Using our modified conditions DD-PCR efficiently screens a wide range of gene expression levels, in which differences are represented on a linear scale.


H₂receptor-mediated positive inotropic effect of histamine in neonatal guinea-pig left atria.
The receptor type mediating the positive inotropic effect of histamine was examined in left atria from neonatal guinea pigs. The positive inotropic effect of histamine, as well as its action potential prolonging effect, was antagonized by ranitidine, but not by chlorpheniramine or thiperamide. The positive inotropic effect was enhanced by isobutylmethylxantine. Receptor binding studies revealed the presence of both H₁ and H₂ receptor types. These results suggest that the positive inotropic effect of histamine in the neonatal guinea-pig atrium is mediated by H₂ receptors.


Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals.
Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses' mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses' mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses' mental models: "conscious decision-making"; "medication-related fears"; "practice-based observations"; and "risk assessment". They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Nurses in both countries employ analytical and affective mental models when administering the opioids and seem to learn from experience rather than from formal teaching. Additionally, some attitudes and emotions towards opioids are likely the result of nurses' cultural background.


Highly-accurate solvent identification using dynamic evaporation reflection spectra from an inverse opal sensor combined with a deep learning model.
Developing a low-cost, rapid, and highly accurate method for detecting solvents with similar structures and properties is highly demanded. In recent years, methods based on dynamic reflection spectroscopy have been developed to distinguish isomers and homologues. However, these methods heavily rely on responsive photonic crystals that can interact intricately with the solvent. In this work, we propose a deep learning approach for direct solvent identification from dynamic evaporative reflection spectra (DERS) obtained on a simple inverse opal (IO) sensor. The sensor was prepared using co-assembly and sacrificial template methods. Then, a dataset was constructed with 985 DERS obtained from 14 different solvents. Different classical machine learning and deep learning algorithms were employed for classifying these DERS. The results showed that ResNet18-CBAM, an improved convolutional neural network, outperformed all other algorithms, achieving 97.7 ± 0.9% on the 5-fold cross-validation set and 100% accuracy on the test set. This strategy presents not only a simple, efficient, and repeatable method for solvent detection but also, more importantly, by integrating the deep learning model, it allows an automatic, rapid, and accurate analysis of DERS data without the need for human intervention. It holds great application prospects in the field of solvent detection.


Preferential killing of triple-negative breast cancer cells in vitro and in vivo when pharmacological aggravators of endoplasmic reticulum stress are combined with autophagy inhibitors.
The cellular processes of autophagy and endoplasmic reticulum stress (ERS) appear to be interconnected, and it has been proposed that autophagy may serve to reduce ERS via removal of terminally misfolded and aggregated proteins. Conversely, there are indications that blockage of autophagy may increase ERS. Based on earlier work demonstrating that pharmacologically aggravated ERS can result in tumor cell killing, we investigated whether blockage of autophagy would enhance this effect in a therapeutically useful manner. We therefore combined chloroquine (CQ), a pharmacological inhibitor of autophagy, with other drugs known to act as ERS aggravators (ERSA), namely nelfinavir (an HIV protease inhibitor) and celecoxib (a cyclooxygenase-2 inhibitor) or its non-coxib analog 2,5-dimethyl-celecoxib (DMC), and investigated combination drug effects in a variety of breast cancer cell lines. We found that the addition of CQ resulted in synergistic enhancement of tumor cell killing by ERSA compounds, particularly in triple-negative breast cancer (TNBC) cells. This combination effect could also be confirmed in an in vivo model, where CQ boosted low-dose ERSA effects, resulting in rapid deterioration of xenografted tumors in mice. Altogether, our results indicate that combinations of an autophagy inhibitor with pharmacological ERSA (i.e. compounds that lead to ER stress aggravation) should be further explored for potential therapy of otherwise difficult-to-treat TNBC.


[Equipment for epiduroscopy and its clinical applications].
Equipments for epiduroscopy consist of an epidural endoscope, video camera system, video screen, recording system and C arm X-ray system. Epidural endoscope with a diameter of 0.9 mm is inserted from the hiatus sacralis, and has been used clinically for the observation of epidural space of a lumbar vertebrae level since 1996. There are still some problems to be solved in the epiduroscope development, but its dramatic pain reduction effect has been recognized and it has been held as an attractive diagnostic tool.


Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis.
Background and study aims There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group. Results The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I2 = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success.


Chronic Fatigue Predicts Hospital Nurse Turnover Intentions.
The objective of this study was to determine the impact of workforce engagement factors on hospital nurse turnover intentions. Nurse turnover intentions are impacted by occupational fatigue and burnout, which are differentially impacted by fatigue, meaning and joy in work, and work-related resilience. One hundred fifty-one nurses from a southwestern hospital completed online surveys. Path analyses evaluated relationships among variables. Chronic occupational fatigue was the only significant predictor of turnover intentions among nurses. Although strongly associated with emotional exhaustion and depersonalization (burnout components), burnout did not predict turnover intention. High levels of chronic fatigue predicted lower meaning and joy in work and lower work-related resilience. Although significantly correlated, meaning and joy in work and resilience did not predict total burnout scores when analyzed in causal models. Nurse administrators should focus efforts on factors such as chronic occupational fatigue that are likely to impact nurses' decisions to leave their positions.


Polypoid lesions of the gallbladder.
Polypoid lesions of the gallbladder encompass a wide variety of pathology. Although most of these lesions are benign, some early carcinomas of the gallbladder do present as polypoid lesions. Problems remain in selecting patients with polypoid lesions of the gallbladder for surgery, the operative approach, and the method of follow-up of those deemed not needing surgery. This review was done by Medline search of the English literature by the keywords "polypoid lesions of gallbladder," "gallbladder polyps," "carcinoma of gallbladder," and "benign tumors of gallbladder." Most small polypoid lesions of the gallbladder are benign and remain static for years. Three- to six-monthly ultrasonography examination is warranted in the initial follow-up period but it is probably unnecessary after 1 or 2 years. Age more than 50 years and size of polyp more than 1 cm are the two most important factors predicting malignancy in polypoid lesions of the gallbladder. Other risk factors include concurrent gallstones, solitary polyp, and symptomatic polyp. Laparoscopic cholecystectomy is the treatment of choice unless the suspicion of malignancy is high, in which case it is advisable to have open exploration, intraoperative frozen section, and preparation for extended resection.


Transjugular intrahepatic portosystemic shunt for treatment of intractable colonic ischemia associated with portal hypertension: a bridge to liver transplantation.
A 64-year-old man with portal hypertension secondary to hepatic nodular transformation was awaiting liver transplantation when he presented with severe, unrelenting abdominal pain, fever, and hypotension. Computed tomographyrevealed pneumatosis within the cecum and ascending colon. Because of his advanced liver disease and the perceived high likelihood of a poor outcome after colonic resection, he was managed medically. He improved initially but had a lengthy hospital course notable for intractable intestinal ischemia and gastrointestinal bleeding. Magnetic resonance angiography demonstrated patent mesenteric, portal, and hepatic vessels. His blood pressure was typically 90/55 mm Hg (mean arterial pressure, 65-70 mm Hg) despite intravenous fluids and blood product replacement. The hypothesis developed that the patient's level of portal hypertension was sufficiently severe (in the face of his low mean systemic arterial pressure) to compromise perfusion of the colonic mucosa. Were this hypothesis correct, then portal decompression might enhance the blood pressure gradient across the bowel and improve mucosal perfusion. With this in mind, a transjugular intrahepatic portosystemic shunt (TIPS) was placed. There was reduction of the portal vein to inferior vena cava gradient from 29 mm Hg to 9 mm Hg and his abdominal pain and gastrointestinal bleeding ceased. His prompt and sustained improvement following TIPS shunt placement is consistent with the hypothesis that high portal pressure was flow limiting, thus contributing to persisting intestinal ischemia. This case represents the first report of use of a TIPS shunt to address colonic ischemia associated with portal hypertension.


Dynamic changes of the luminal plasmalemma in stimulated parotid acinar cells. A freeze-fracture study.
In the acinar cells of the rat parotid gland the two membranes participating in exocytosis, i.e., the luminal plasmalemma and the secretory granule membrane, are clearly distinguishable in freeze-fracture because of their different densities in particles. In order to obtain point-specific information about the fusion-fission of these two membranes that occurs during the secretory cycle, glands were studied at various times (5 min to 6 h) after stimulation with isoproterenol. We observed that, in the course of the release of secretion products and shortly afterwards, the enlarged luminal plasmalemma exhibits a mosaic organization consisting of an alternation of membrane patches of high (original plasmalemma) and low (fused granule membrane) particle density. The transition between these two patterns is usually sharp. Later, concomitant with the reformation of acinar canaliculi, the low particle density membrane is found at the cell surface but only bounding vacuolar infoldings, and then it finally disappears. These results suggest that (a) fusion of these membranes does not result in a random intermixing of the molecular components of the participating membranes, which retain their structural identity; and (b) the enlarged luminal plasmalemma reverts to its original size by a progressive, specific removal of the regions of low particle density from the cell surface.


Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo.
Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of enhancer RNAs (eRNAs) that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.


[PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position improves urinary continence and protects erectile function in BPH patients].
To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11-1 o'clock position on urinary continence and erectile function in BPH patients. We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% [24/36] vs 43.25% [20/48], P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% [12/36] vs 56.25% [28/48], P = 0.018) and 12 months (25% [9/36] vs 47.92% [23/48], P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). Modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.


[A man with FIP1L1/PDGFRA-positive chronic eosinophilic leukemia].
A 39-year-old man was referred from Surinam to the Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands, for a right ventricular tumour, hypereosinophilia and mild thrombocytopenia. He appeared to have chronic eosinophilic leukaemia that was positive for the 'FIP1-like-1-platelet-derived growth factor receptor alpha' (FIP1L1-PDGFRA) gene. In addition, he had signs of a right ventricular thrombus that had existed for at least 6 months. The patient was treated with oral anticoagulants and the tyrosine kinase inhibitor imatinib. The latter therapy resulted in normalisation of leukocyte count and differential values. After 3 months of therapy, the FIP1L1-PDGFRA fusion transcript was no longer detectable in peripheral blood. After 1 year of follow up, the patient was in complete haematological and molecular remission for chronic eosinophilic leukaemia. The cardiac mass remained unchanged, but caused no haemodynamic problems.


Insights into the Antioxidant/Antiradical Effects and In Vitro Intestinal Permeation of Oleocanthal and Its Metabolites Tyrosol and Oleocanthalic Acid.
(1) Background: In recent years, numerous studies have highlighted the beneficial effects of extra virgin olive oil (EVOO) as an active ingredient against chronic diseases. The properties of EVOO are due to its peculiar composition, mainly to its rich content of polyphenols. In fact, polyphenols may contribute to counteract oxidative stress, which often accompanies chronic diseases. In this work, the antioxidant effects of high-value polyphenol oleocanthal (OC) and its main metabolites, tyrosol (Tyr) and oleocanthalic acid (OA), respectively, have been investigated along with their impact on cell viability. (2) Methods: OC, Tyr, and OA have been evaluated regarding antiradical properties in term of scavenging capacity towards biologically relevant reactive species, including O2●-, HOCl, and ROO●, as well as their antioxidant/antiradical capacity (FRAP, DPPH●, ABTS●+). Moreover, the ability to permeate the intestinal membrane was assessed by an intestinal co-culture model composed by Caco-2 and HT29-MTX cell lines. (3) Results: The capacity of OC and Tyr as radical oxygen species (ROS) scavengers, particularly regarding HOCl and O2●-, was clearly demonstrated. Furthermore, the ability to permeate the intestinal co-culture model was plainly proved by the good permeations (>50%) achieved by all compounds. (4) Conclusions: OC, OA, and Tyr revealed promising properties against oxidative diseases.


Shortened sleep fuels inflammatory responses to marital conflict: Emotion regulation matters.
Sleep problems can boost inflammation and may jeopardize interpersonal functioning, risks that may be magnified in couples. This observational study examined the effects of self-reported recent sleep duration on couples' inflammation, inflammatory responses to a problem discussion, interpersonal behavior, and use of emotion regulation strategies (emotion expression, cognitive reappraisal) during conflict. People who slept less had higher stimulated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production after the marital problem discussion than those who slept more. However, using emotion expression and cognitive reappraisal strategies during conflict protected couples who slept less from inflammatory reactivity. Specifically, people's short sleep did not relate to inflammatory increases when they expressed their own feelings more or when their partner reappraised or expressed their emotions more. When both partners slept less, couples interacted in a more hostile way than when at least one partner slept more. These data point to the combination of short sleep and marital conflict as a novel path to heightened inflammation, a risk that partners' emotion regulation strategies may counteract. The study also highlights the role of short sleep in more negative or punishing marital behavior.


Image-Based Models for Specularity Propagation in Diminished Reality.
The aim of Diminished Reality (DR) is to remove a target object in a live video stream seamlessly. In our approach, the area of the target object is replaced with new texture that blends with the rest of the image. The result is then propagated to the next frames of the video. One of the important stages of this technique is to update the target region with respect to the illumination change. This is a complex and recurrent problem when the viewpoint changes. We show that the state-of-the-art in DR fails in solving this problem, even under simple scenarios. We then use local illumination models to address this problem. According to these models, the variation in illumination only affects the specular component of the image. In the context of DR, the problem is therefore solved by propagating the specularities in the target area. We list a set of structural properties of specularities which we incorporate in two new models for specularity propagation. Our first model includes the same property as the previous approaches, which is the smoothness of illumination variation, but has a different estimation method based on the Thin-Plate Spline. Our second model incorporates more properties of the specularity's shape on planar surfaces. Experimental results on synthetic and real data show that our strategy substantially improves the rendering quality compared to the state-of-the-art in DR.


Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.
Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals. The study included 34 renal transplant patients with histologically proven CAN and 36 patients with normal renal transplant function. High-throughput proteomic profiles were generated from urine samples with three different ProteinChip arrays by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Following SELDI, a biomarker pattern software analysis was performed which led to the identification of a novel biomarker pattern that could distinguish patients with CAN from those with normal renal function. An 11.7 kDa protein identified as β2 microglobulin was the primary protein of this biomarker pattern, distinguishing CAN from control patients (receiver operator characteristic [ROC]=0.996). SELDI-TOF-MS comparison of purified β2 microglobulin protein and CAN urine demonstrated identical 11.7 kDa protein peaks. Significantly, higher concentrations of 2 microglobulin were found in the urine of patients with CAN compared with the urine of normal renal function transplant recipients (p<0.001). Although further validation in a larger more diverse patient population is required to determine if this β2 microglobulin protein biomarker will provide a potential means of diagnosing CAN by noninvasive methods in a clinical setting, this study clearly shows a capability to stratify control and disease patients.


Aging sexual stereotypes and sexual expression in mid- and later life: examining the stereotype matching effect.
Ageist sexual stereotypes may prohibit midlife and older adults from achieving sexual wellness when stereotypical beliefs about aging, sex, and intimacy become internalized over the life course (i.e. stereotype embodiment). Though there are several studies examining the application of stereotype embodiment theory to various health behaviors, it has not been applied to sexual and intimate health across the life course. The current study examined sexual stereotype embodiment by assessing the impact of aging-sexual-stigma on sexual and intimate activity among midlife and older adults. In this cross sectional study, a convenience sample of 972 adults aged 50 and older was recruited via a crowdsourcing platform. Participants completed an online survey assessing attitudes about aging sexuality and their participation in a spectrum of sexual and intimate behaviors. Hierarchical linear regression was used to examine the study hypotheses related to sexual and intimate behaviors among middle age and older adults. Results of this exploratory study suggest that embodiment of sexual stereotypes effects both midlife and older adults, with endorsement of aging sexual stigma predicting lower engagement in both sexual and intimate activities. Sexual embodiment had similar effects across age cohort and gender. In addition to pervasive societal impact, ageist sexual stereotypes appear to affect individual sexual health and wellness via internalized beliefs. This provides preliminary evidence for stereotype embodiment in a novel domain, sexual health. Future research should explore potential age and cohort effects across the life course in longitudinal studies with robust measures of aging sexual stigma.


Gene down-regulation with short hairpin RNAs and validation of specificity by inducible rescue in mammalian cells.
The principal problem with RNA interference (RNAi) experiments is off-target effects. The most vigorous demonstration of the specificity is the rescue of the RNAi effects with an RNAi-resistant target gene. By combining the expression of short hairpin RNA (shRNA) and rescue cDNA in the same vector, both the validation of shRNA specificity and the generation of shRNA-expressing cell lines can easily be accomplished. If the compensatory cDNA is under the control of an inducible promoter, stable shRNA-expressing cells can be generated before the knockdown phenotypes are studied, by conditionally turning off the rescue protein. The use of model systems is detailed in these protocols.


The curli biosynthesis regulator CsgD co-ordinates the expression of both positive and negative determinants for biofilm formation in Escherichia coli.
Production of curli, extracellular structures important for biofilm formation, is positively regulated by OmpR, which constitutes with the EnvZ protein an osmolarity-sensing two-component regulatory system. The expression of curli is cryptic in most Escherichia coli laboratory strains such as MG1655, due to the lack of csgD expression. The csgD gene encodes a transcription activator of the curli-subunit-encoding csgBA operon. The ompR234 up-mutation can restore csgD expression, resulting in curli production and increased biofilm formation. In this report, it is shown that ompR234-dependent csgD expression, in addition to csgBA activation during stationary phase of growth, stimulates expression of the yaiC gene and negatively regulates at least two other genes, pepD and yagS. The promoter regions of these four genes share a conserved 11 bp sequence (CGGGKGAKNKA), necessary for csgBA and yaiC regulation by CsgD. While at both the csgBA and yaiC promoters the sequence is located upstream of the promoter elements, in both yagS and pepD it overlaps either the putative -10 sequence or the transcription start point, suggesting that CsgD can function as both an activator and a repressor. Adhesion experiments show that csgD-independent expression of both yagS and pepD from a multicopy plasmid negatively affects biofilm formation, which, in contrast, is stimulated by yaiC expression. Thus it is proposed that CsgD stimulates biofilm formation in E. coli by contemporary activation of adhesion positive determinants (the curli-encoding csg operons and the product of the yaiC gene) and repression of negative effectors such as yagS and pepD.


Prevalence of hypovitaminosis D in India & way forward.
Deficiency of vitamin D or hypovitaminosis D is widespread irrespective of age, gender, race and geography and has emerged as an important area of research. Vitamin D deficiency may lead to osteoporosis (osteomalacia in adults and rickets in children) along with calcium deficiency. Its deficiency is linked with low bone mass, weakness of muscles and increased risk of fracture. However, further research is needed to link deficiency of vitamin D with extra-skeletal consequences such as cancer, cardiovascular disease, diabetes, infections and autoimmune disorders. The causes of vitamin D deficiency include length and timing of sun exposure, amount of skin exposed, latitude, season, level of pollution in atmosphere, clothing, skin pigmentation, application of sunscreen, dietary factors and genetic factors. The primary source is sunlight, and the dietary sources include animal products such as fatty fish, food items fortified with vitamin D and supplements. Different cut-offs have been used to define hypovitaminosis D and its severity in different studies. Based on the findings from some Indian studies, a high prevalence of hypovitaminosis D was observed among different age groups. Hypovitaminosis D ranged from 84.9 to 100 per cent among school-going children, 42 to 74 per cent among pregnant women, 44.3 to 66.7 per cent among infants, 70 to 81.1 per cent among lactating mothers and 30 to 91.2 per cent among adults. To tackle the problem of hypovitaminosis D in India, vitamin D fortification in staple foods, supplementation of vitamin D along with calcium, inclusion of local fortified food items in supplementary nutrition programmes launched by the government, cooperation from stakeholders from food industry and creating awareness among physicians and the general population may help in combating the problem to some extent.