Hyperprolinaemia: a disease which does not need treatment?
The authors observed two cases of hyperprolinaemia (one of type I and the other of type II) which were asymptomatic. The anomalies described up to the present time in association with hyperprolinaemia are inconstant, nonspecific, and extremely heterogeneous. This suggests that the relationship between hyperprolinaemia and other anomalies is purely coincidental, and that a therapeutic approach by diet is unjustified.


Hemocompatibility of hydrophilic antimicrobial copolymers of alkylated 4-vinylpyridine.
Quaternized poly(vinylpyridine) (PVP) is a polymer with inherent antimicrobial properties that is effective against Gram-positive bacteria, Gram-negative bacteria, viruses, and yeast cells. However, quaternized PVP has poor biocompatibility, which prevents its use in biomaterial applications. Copolymerization was examined as a method of modifying the structure to incorporate biocompatibility. Polyethyleneglycol methyl ether methacrylate (PEGMA) and hydroxyethyl methacrylate (HEMA) are polymers generally known to be biocompatible and thus were chosen as comonomers. Random copolymers of 4-vinylpyridine and PEGMA or HEMA were synthesized via free radical polymerization and quaternized with bromohexane. Copolymer biocompatibility was characterized by interaction with human red blood cells to analyze hemolysis. Hemolysis of human red blood cells was conducted on insoluble films and on water-soluble polymers in a serial dilution study. Hemolysis results demonstrated that blood compatibility does not depend on PEG chain length in PEGMA incorporated copolymers. Results indicate a critical weight ratio of PEGMA to VP in copolymers separating the no-hemolysis regime from 100% hemolysis.


Epigenetics meets radiation biology as a new approach in cancer treatment.
Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment. Especially, colon cancer is a great model system for investigating the epigenetic mechanism for aberrant gene expression alteration. Ionizing radiation (IR) could affect a variety of processes within exposed cells and, in particular, cause changes in gene expression, disruption of cell cycle arrest, and apoptotic cell death. Even though there is growing evidence on the importance of epigenetics and biological processes induced by radiation exposure in various cancer types including colon cancer, specific epigenetic alterations induced by radiation at the molecular level are incompletely defined. This review focuses on discussing possible IR-mediated changes of DNA methylation and histone modification in cancer.


Molecular characterization of genes responsible for biofilm formation in Staphylococcus aureus isolated from mastitic cows.
Mastitis is considered a significant disease of lactating animals. There are new attitudes for recognizing genes responsible for causing this disease to overcome and change the manipulation of this problem. This study aimed to isolate and identify Staphylococcus aureus strains from mastitic bovine animals and detect some specific biofilm-forming genes (icaA, icaD, and biofilm-associated protein [bap] genes clfA, fnbA, agrI, agrII, agrIII, agrIV, and cna). A total of 121 mastitic milk samples were analyzed using biochemical tests (catalase test, oxidative-fermentative test, and coagulase test) and Gram stain. Multiplex polymerase chain reaction was applied to characterize biofilm genes (icaA, icaD, bap, clfA, and fnbA) in addition to (agrI, agrII, agrIII, agrIV, and cna). Among the 121 milk samples, 35 staphylococci isolates were derived with an incidence of 28.92% (35/121); among them, 19 are coagulase positive. Ninety percent of the isolates had ica genes (icaA and icaD) while bap gene was not recognized in any isolate. In addition, the incidence of fnbA, can, and clfA was 89.5% each. The prevalence of agr specific groups (agrI, agrII, agrIII, and agrIV) was 78.9%, 52.6%, 10.5%, and 15.8%, respectively. This study concluded that S. aureus has variant mechanisms of pathogenicity to form biofilm devoid of carrying a specific gene.


Phytosomal bilayer-enveloped casein micelles for codelivery of monascus yellow pigments and resveratrol to breast cancer.
Multireservoir nanocarriers were fabricated for delivering antineoplastic drug cocktail from herbal and fungal origin. Monascus yellow pigments (MYPs), monascin and ankaflavin, were isolated from red-mold rice, and incorporated within casein micelles (CAS MCs) along with the herbal drug, resveratrol (RSV). Both drugs (MYPs and RSV) were simultaneously incorporated into the hydrophobic core of CAS MCs. Alternatively, MYPs-loaded CAS MCs were enveloped within RSV-phytosomal bilayer elaborating multireservoir nanocarriers. Cytotoxicity studies confirmed the superiority of multireservoir nanocarriers against MCF-7 breast cancer cells. The in vivo antitumor efficacy was revealed by reduction of the tumor volume and growth biomarkers. Multireservoir CAS nanocarriers for codelivery of both MYPs and RSV may be promising alternative to traditional breast cancer therapy.


Gonorrhea rates rising among hardest-hit.
At the very time when the nation's syphilis infection rates are declining and when new tests make it easier to detect and treat chlamydia, there is a dark cloud on the horizon: more than 60% of the cities that have been hardest hit by gonorrhea infection have experienced increases in the infection rate between 1999 and 2000.


Mechanisms of repeat-associated non-AUG translation in neurological microsatellite expansion disorders.
Repeat-associated non-AUG (RAN) translation was discovered in 2011 in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1). This non-canonical form of translation occurs in all reading frames from both coding and non-coding regions of sense and antisense transcripts carrying expansions of trinucleotide to hexanucleotide repeat sequences. RAN translation has since been reported in 7 of the 53 known microsatellite expansion disorders which mainly present with neurodegenerative features. RAN translation leads to the biosynthesis of low-complexity polymeric repeat proteins with aggregating and cytotoxic properties. However, the molecular mechanisms and protein factors involved in assembling functional ribosomes in absence of canonical AUG start codons remain poorly characterised while secondary repeat RNA structures play key roles in initiating RAN translation. Here, we briefly review the repeat expansion disorders, their complex pathogenesis and the mechanisms of physiological translation initiation together with the known factors involved in RAN translation. Finally, we discuss research challenges surrounding the understanding of pathogenesis and future directions that may provide opportunities for the development of novel therapeutic approaches for this group of incurable neurodegenerative diseases.


[Should the great saphenous vein be stripped in routine surgery for uncomplicated varicose veins?].
Stripping of the great saphenous vein is widely used in the surgical treatment for varicose veins. With the increasing demand of vein material in coronary- and femoro-distal bypass surgery, this routine creates a conflict. A review of the literature reveals the possibility of vein-saving procedures that do not increase the recurrence rates. By utilizing modern diagnostic methods, it is possible to make an exact preoperative diagnosis as to the extent of the varicose disease and thus make an individualized operation, that is just as radical as necessary, but at the same time as vein-preserving as possible.


A novel polyurethane-based biodegradable elastomer as a promising material for skeletal muscle tissue engineering.
A key challenge in skeletal muscle tissue engineering is the choice of a proper scaffolding material as it should demonstrate elastic behavior to withstand and support the dynamic loading of the tissue microenvironment while being biodegradable and biocompatible. In this study, we tested the applicability of a novel biodegradable polyurethane (PU) elastomer chain extended with fibrinogen (Fib) to fulfill these requirements. Biodegradable polyurethane-fibrinogen (PU-Fib) elastomers were synthesized by step-wise condensation polymerization. Firstly, PU prepolymer was synthesized and then Fib was integrated into PU prepolymer during the second step of polymerization. The chemical, thermal, viscoelastic, mechanical and biodegradation properties of PU-Fib were characterized. FTIR-ATR spectrum showed amide bands specific to PU and Fib, DSC thermograms showed the suitable integration between the components. Dynamic mechanical analysis revealed Tg and Tα* transitions at 64.5 °C and 38.4 °C, respectively. PU and Fib had shown chemically compatible interactions and when compared to PCL, PU-Fib possessed viscoelastic properties more suitable to the native tissue. PU-Fib films were produced and seeded with C2C12 mouse myoblasts. Uniaxial cyclic stretch was applied to the cell seeded films for 21 d to mimic the native dynamic tissue microenvironment. Cell proliferation, viability and the expression of muscle-specific markers (immunofluorescent staining for myogenin and myosin heavy chain) were assessed. Myoblasts proliferated well on PU-Fib films; aligned parallel along their long edge, and express myogenic markers under biomimetic dynamic culture. It was possible to culture myoblasts with high viability on PU-Fib elastomeric films mimicking native muscle microenvironment.


CDP-diacylglycerol, a critical intermediate in lipid metabolism.
The roles of lipids expand beyond the basic building blocks of biological membranes. In addition to forming complex and dynamic barriers, the thousands of different lipid species in the cell contribute to essentially all the processes of life. Specific lipids are increasingly identified in cellular processes, including signal transduction, membrane trafficking, metabolic control and protein regulation. Tight control of their synthesis and degradation is essential for homeostasis. Most of the lipid molecules in the cell originate from a small number of critical intermediates. Thus, regulating the synthesis of intermediates is essential for lipid homeostasis and optimal biological functions. Cytidine diphosphate diacylglycerol (CDP-DAG) is an intermediate which occupies a branch point in lipid metabolism. CDP-DAG is incorporated into different synthetic pathways to form distinct phospholipid end-products depending on its location of synthesis. Identification and characterization of CDP-DAG synthases which catalyze the synthesis of CDP-DAG has been hampered by difficulties extracting these membrane-bound enzymes for purification. Recent developments have clarified the cellular localization of the CDP-DAG synthases and identified a new unrelated CDP-DAG synthase enzyme. These findings have contributed to a deeper understanding of the extensive synthetic and signaling networks stemming from this key lipid intermediate.


The current and future role of stem cells in myelodysplastic syndrome therapies.
Allogeneic blood stem cell transplantation (aBSCT) still is the only curative therapy for patients with myelodysplastic syndromes. While it carries the hope for cure for some patients, it may result in severe toxicity and death from complications or recurrent disease in others. Recent developments have improved patient and donor selection as well as technical aspects of the transplant procedure and post-transplant care, including early detection and treatment of relapse. Areas covered: This review will discuss current stratification tools to identify suitable patients, donors and transplant techniques. In addition, it will cover the prognostic and predictive value of cytogenetics and somatic mutations and elucidate strategies for minimal residual disease detection as well as prophylactic and preemptive treatment of recurrent disease. Expert commentary: aBSCT will continue to be the most powerful curative treatment option for patients with MDS. Advances in the understanding of disease biology will allow to incorporate molecular alterations in current prognostic scores, tracking of specific mutations during therapy and the use of novel, targeted therapies to augment the graft versus leukemia effect.


Performance of a Cell-Free DNA-Based Multi-cancer Detection Test in Individuals Presenting With Symptoms Suspicious for Cancers.
A multi-cancer detection test using a targeted methylation assay and machine learning classifiers was validated and optimized for screening in prospective, case-controlled Circulating Cell-free Genome Atlas (ClinicalTrials.gov identifier: NCT02889978) substudy 3. Here, we report test performance in a subgroup of participants with symptoms suspicious for cancer to assess the test's ability to potentially facilitate efficient diagnostic evaluation in symptomatic individuals. We evaluated test performance (sensitivity, specificity, and accuracy of cancer signal origin [CSO] prediction accuracy) in participants with clinically presenting cancers (CPCs) and noncancer with underlying medical conditions and among two subgroups (65 years and older and GI cancers). Overall survival (OS) of participants who had a cancer signal detected/not detected was compared with SEER-based expected survival. A total of 2,036 cancer and 1,472 noncancer participants were included. Specificity was high in all noncancer participants (99.5% [95% CI, 98.4 to 99.8]). In participants with CPCs, the overall sensitivity was 64.3% (95% CI, 62.2 to 66.4) and the overall accuracy of CSO prediction in true positives was 90.3%. For GI cancers, the overall sensitivity was 84.1% (95% CI, 80.6 to 87.1). In participants 65 years and older, test performance was similar to that of all participants. Individuals with cancers not detected had a significantly better OS than that expected from SEER (P < .01). This test detected a cancer signal with high specificity and CSO prediction accuracy and moderate sensitivity in symptomatic individuals, with especially high performance in participants with GI cancers. The survival analysis implied that the cancers not detected were less clinically aggressive than cancers detected by the test, providing prognostic insights to physicians. This multi-cancer detection test could facilitate efficient workup and stratify cancer risk in symptomatic individuals.


Erythropoietin-receptor agonists in critically ill patients: a meta-analysis of randomized controlled trials.
Anemia and the need for red blood cell transfusions are common among patients admitted to intensive care units. Erythropoietin has been used to decrease the need for transfusions; however, its ability to improve clinical outcomes is unknown. We evaluated the effect of erythropoietin-receptor agonists on clinically important outcomes, including mortality, length of stay in hospital or intensive care unit, ventilator use, transfusion requirements and major adverse events. To identify relevant studies, we searched electronic databases covering 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Scopus database). We also searched conference proceedings and grey literature sources. We selected all randomized controlled trials involving critically ill patients that compared an erythropoietin-receptor agonist with a placebo or no intervention. No language restrictions were considered. Data were extracted using a standardized extraction template. We used a fixed effects model to calculate all summary measures of treatment effects. Of 673 identified records, 9 studies that investigated erythropoietin alpha met the eligibility criteria and were included in our analysis. Erythropoietin, compared with placebo or no intervention, had no statistically significant effect on overall mortality (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.71-1.05, I2 = 0%). The treatment and control groups did not differ in the length of stay in hospital or intensive care unit, or in the duration of mechanical ventilation, in the 3 studies that reported these outcomes. Erythropoietin, compared with placebo, significantly reduced the odds of a patient receiving at least 1 transfusion (OR 0.73, 95% CI 0.64-0.84, I2 = 54.7%). The mean number of units of blood transfused per patient was decreased by 0.41 units in the erythropoietin group (95% CI 0.10-0.74, I2 = 79.2%). Most of the included studies were performed before the widespread adoption of a restrictive transfusion strategy. Only 1 study provided detailed reports of adverse events, and none of the studies systematically evaluated all patients for venous thromboembolism. At this time, we do not recommend the routine use of erythropoietin-receptor agonists in critically ill patients. The reduction in red blood cell transfusions per patient was very small, and there is insufficient evidence to determine whether this intervention results in clinically important benefits with acceptable risks.


Analysis of proteins and lipopolysaccharides from Chinese isolates of Coxiella burnetii with monoclonal antibodies.
Four Coxiella burnetii isolates in China and two reference strains were compared by SDS-PAGE and immunoblotting. The SDS-PAGE profiles of whole cells and LPS of Chinese isolates Qiyi, Xinqiao, and YS-8 were found closely related to Henzerling strain, and different from the Grita strain. In immunoblot assay of LPS and proteinase K-digested whole rickettsiae minor differences were seen in polysaccharide structure among the Chinese isolates by phase I monoclonal antibody. The present results suggest that the strains reported here may be divided into three groups according to the polysaccharide structure: Xinqiao and Henzerling strains (1), YS-8 and Grita (2), and Qiyi (3).


Abdominal complications after cardiac surgery in cardiopulmonary bypass.
Gastrointestinal problems are an infrequent but serious consequence of cardiac surgery that includes cardiopulmonary bypass. Predictors of these complications are not well developed, and the role of fundamental variables remains controversial. Between July 1998 and August 2002, 1,552 patients (1,106 male and 446 female), mean age 56 years, underwent heart surgery with cardiopulmonary bypass. Among those 1,552 patients, 21 (1.35%) had gastrointestinal complications, mainly because of gastrointestinal bleeding due to gastritis and five of them required surgery. We present these five patients, three with intestinal ischemia, two with intestinal bleeding. There Hoffmeister-Finsterer operation, Rydygier resection, hemicolectomy, appendectomy with cecum sewing and sigmoid resection were performed. The mortality in this group was 60% (three of five), and the cause of death was multiorgan insufficiency. Careful monitoring and physical examination of these high-risk patients following cardiac surgery is required for early detection and effective treatment.


Hepatic artery thrombosis and infarction: evolution of the ultrasound appearances in liver transplant recipients.
Hepatic infarction is a serious complication of liver transplantation, causing significant morbidity and mortality and often requiring retransplantation. Real time ultrasonography with Doppler examination is often the first imaging modality employed to investigate post-operative complications. We report on the sonographic appearances of three patients in whom hepatic infarction followed transplantation but who did not require retransplantation, allowing us to study the evolution of sonographic features. Geographic areas of decreased echogenicity with preservation of the portal tracts are an early sign of hepatic ischaemia and may either resolve completely or progress to true infarction with the development of transient small hyperechoic lesions. Calcification may also occur quite rapidly. Biliary strictures, bilomas and abscess formation are later complications.


Establishment of Epithelial Inflammatory Injury Model Using Intestinal Organoid Cultures.
Intestinal epithelial dysfunction is critical in the development of inflammatory bowel disease (IBD). However, most cellular experiments related to epithelial barrier studies in IBD have been based on tumor cell line that lack a variety of intestinal epithelial cell types. Thus, intestinal organoids can present the three-dimensional structure and better simulate the physiological structure and function of the intestinal epithelium in vitro. Here, the crypts were isolated from the small intestine of mice; with the participation of major cytokines (EGF, Noggin, and R-Spondin 1 included), the intestinal organoids were established at a density of 100 crypts per well, containing intestinal stem cells (ISC), Paneth cells, goblet cells, and intestinal endocrine cells. We found that tumor necrosis factor-alpha (TNF-α) could induce the inflammatory response of intestinal organoids, and a dose of 10 ng/mL could maintain stable passaging of organoids for dynamic observation. After stimulation with TNF-α, the intestinal organoid cultures showed lower expression of the cell proliferation-related protein identified by monoclonal antibody Ki 67 (Ki67), the ISC marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), and the intestinal tight junction proteins occludin (Ocln) and claudin-1 (Cldn1) while higher expression of the inflammatory cytokine interleukin- (IL-) 15 and the chemokines C-X-C motif ligand 2 (Cxcl2) and Cxcl10 significantly. In this study, we successfully established an epithelial inflammatory injury model of intestinal organoids, which provides an effective in vitro model for studying the pathogenesis and treatment of IBD.


Fibrocystic change of the breast presenting as a focal lesion mimicking breast cancer in MR imaging.
Focal fibrocystic change (FCC) of the breast is a rare form of FCC. Imaging presentations of focal FCC are not well known. This study aimed to analyze its MR imaging features. Eleven patients of pathology-proven focal FCC were retrospectively studied. Of the 11 patients, seven were mass (>or=5 mm), two showed multiple foci, and two were focus (<5 mm). The lesion size ranged from 4-12 mm (mean 6.7 mm). Morphologically, three patients were suspected as malignancy. Using kinetic enhancement curve, 8 of 13 lesions were suspected to be malignant. Overall, nine patients (82%) were suspected for malignancy using either criterion. Using mammography, 6 of the 11 patients (55%) were diagnosed as malignancy. Breast sonography suspected malignancy in seven patients (7/10, 70%). No statistically significant difference was found in the three diagnostic methods. In pathology, all 11 patients showed the typical pathological features of fibrocystic change, with mixed components of stromal fibrosis, cyst formation, apocrine metaplasia, adenosis, and/or focal sclerosing adenosis. In conclusion, MR imaging features of focal FCC usually present as a mass or focus lesion with rapid enhancement and washout kinetics that mimic a malignant breast lesion and lead to unnecessary operation, especially in patients with contralateral malignant breast cancer.


Linezolid for the treatment of complicated skin and skin structure infections in children.
Gram-positive pathogens are a major cause of complicated skin and skin structure infections (CSSSIs) in children. Many pathogens are developing decreased susceptibility to currently used antibiotics, increasing the need for new therapies. Linezolid is well-tolerated and effective in the treatment of these infections in adults. To evaluate the clinical efficacy and safety of iv/oral linezolid and iv vancomycin in children with Gram-positive CSSSIs. Hospitalized children <12 years of age were randomized (2:1 ratio) to receive either linezolid 10 mg/kg iv every 8 h (with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h) or iv vancomycin 10 to 15 mg/kg every 6 to 24 h (according to age). Clinical response, tolerance and safety were evaluated at follow-up. The results of a subset analysis of patients with CSSSIs are presented here. One hundred twenty intent-to-treat patients (linezolid 80, vancomycin 40) with CSSSI were included in this analysis. Clinical cure rates for clinically evaluable patients with CSSSI did not differ between treatment groups (linezolid, 93.2% vs. vancomycin, 90.0%; P = 0.594). Significantly fewer linezolid-treated patients experienced drug-related adverse events than did vancomycin-treated patients (23% vs. 48%; P = 0.006). The percentages of patients with laboratory abnormalities, including selected hematologic parameters, were generally low and similar between the treatment groups. Linezolid given iv or orally was well-tolerated and safe. It was as effective as vancomycin in treating children with Gram-positive CSSSIs.


Glycosylation mediates up-regulation of a potent antiangiogenic and proatherogenic protein, thrombospondin-1, by glucose in vascular smooth muscle cells.
Accelerated development of atherosclerotic lesions remains the most frequent and dangerous complication of diabetes, accounting for 80% of deaths among diabetics. However, our understanding of the pathways mediating glucose-induced gene expression in vascular cells remains controversial and incomplete. We have identified an intracellular metabolic pathway activated by high glucose in human aortic smooth muscle cells that mediates up-regulation of thrombospondin-1 (TSP-1). TSP-1 is a potent antiangiogenic and proatherogenic protein that may represent an important link between diabetes and vascular complications. Using different glucose analogs and metabolites sharing distinct, limited metabolic steps with glucose, we demonstrated that activation of TSP-1 transcription is mediated by the hexosamine pathway of glucose catabolism, possibly resulting in modulation of the activity of nuclear proteins activity through their glycosylation. Specific inhibitors of glutamine: fructose 6-phosphate amidotransferase (GFAT), an enzyme controlling the hexosamine pathway, as well as direct inhibitors of protein glycosylation efficiently inhibited TSP-1 transcription and the activity of a TSP-1 promoter-reporter construct stimulated by high glucose. Overexpression of recombinant GFAT resulted in increased TSP-1 levels. Pharmacological inhibition of GFAT or protein glycosylation inhibited increased proliferation of human aortic smooth muscle cells caused by glucose. We have demonstrated that the hexosamine metabolic pathway mediates up-regulation of TSP-1 by high glucose. Our results suggest that the hexosamine pathway and intracellular glycosylation may control important steps in initiation and development of atherosclerotic lesions.


A three-factor benefits framework for understanding consumer preference for scented household products: psychological interactions and implications for future development.
Humans have deliberately scented their environment for purpose or pleasure for millennia. In the contemporary marketplace most consumers prefer and purchase scented versions of common household products. However, the drivers of this consumer preference have not been elucidated. To explain the attraction to scent in household products we propose a novel three-factor framework, comprising functional benefits (malodor mitigation, base odor coverage, freshening), in-use experience benefits (cleanliness, efficacy, pleasure), and emotional benefits (increasing in confidence, mood and nostalgia). To support this framework, we present new data from a market research survey on US consumer purchasing habits and attitudes towards home cleaning, laundry, and air freshening products. Further substantiating our framework, a focused review of olfactory psychological science illustrating the central role of scent in cognition, wellbeing, motivated behavior, and social behavior, as well as sensory marketing research highlights the benefits and implications of scent in consumer household products. Based on our three-factor framework we go on to discuss the potential for scent to influence health and raise issues to consider (such as potential negative responding to fragranced products). We conclude by showcasing new opportunities for future research in olfactory science and on scented household products that can advance the positive impacts of scent.


A catalytic multicomponent coupling reaction for the enantioselective synthesis of spiroacetals.
The first multicomponent catalytic asymmetric synthesis of spiroacetals has been described. Hybrid molecules comprising a spiroacetal scaffold (a natural-product inspired scaffold) and an α-amino acid motif (a privileged fragment) are easily available through a gold phosphate-catalysed one-pot three component coupling reaction of alkynols, anilines and glyoxylic acid.


Cigarette smoking among adults--United States, 2001.
One of the national health objectives for the United States for 2010 is to reduce the prevalence of cigarette smoking among adults to > or =12% (objective 27.1a). To assess progress toward this objective, CDC analyzed self-reported data from the 2001 National Health Interview Survey (NHIS). The findings of this analysis indicate that, in 2001, approximately 22.8% of U.S. adults were current smokers compared with 25.0% in 1993. During 1965-2001, smoking prevalence declined faster among non-Hispanic blacks aged > or =18 years than among non-Hispanic whites the same age. Preliminary data for January-March 2002 indicate a continuing decline in current smoking prevalence among adults overall. However, the overall decline in smoking is not occurring at a rate that will meet the national health objective by 2010. Increased emphasis on a comprehensive approach to cessation that comprises educational, economic, clinical, and regulatory strategies is required to further reduce the prevalence of smoking in the United States.


[Tuberculosis in the central register for tuberculosis].
Applied methods and results of antituberculosis treatment of all registered patients in 1990 in Poland are presented. Tuberculosis prevention was achieved in 91.9% of sputum-positive patients similarly, diagnostic mistakes were detected in 10% patients with non-bacteriologically determined tuberculosis. In one year since registration 7.7% of sputum-positive patients and 3.9% of patients with non-bacteriologically confirmed tuberculosis have been dying in one year since registration time. Majority of patients in Poland were treated too long because of tuberculosis.


Silver-assisted chemical etching on silicon with polyvinylpyrrolidone-mediated formation of silver dendrites.
Metal-assisted chemical etching (MaCE) on silicon (Si)-mediated by polyvinylpyrrolidone (PVP)-is systematically investigated herein. It is found that the morphologies and crystallographic natures of the grown silver (Ag) dendrites can be significantly modulated, with the presence of PVP in the MaCE process leading to the formation of faceted Ag dendrites preferentially along the (111) crystallographic phase, rather than along the (200) phase. Further explorations of the PVP-mediated effect on Si etching are also revealed. In contrast to the aligned Si nanowires formed by MaCE without PVP addition, only distributed nanopores with sizes of 200 to 400 nm appear on the Si surfaces in the presence of PVP. The origin of surface polishing on Si in the PVP-mediated MaCE process can be attributed to the distinct transport pathway of holes supplied by the Ag(+) ions, where the holes are injected directly into the primary Ag seeds, rather than through Ag dendrites, thus leading to the isotropic etching of the Si surface.


The extended deep inferior epigastric pedicle flap for lower extremity reconstruction.
Large soft-tissue defects of the lower extremity can present a challenging reconstructive problem. The extended deep inferior epigastric pedicle flap is a versatile and reliable flap that can be used for the coverage of complex lower extremity soft-tissue defects as far distal as the knee. We reviewed our 5-year experience with 20 consecutive extended deep inferior epigastric pedicle flaps used to cover lower extremity defects. All wounds, including 4 soft-tissue defects of the knee, were successfully covered. Two minor complications occurred. Flap anatomy, surgical approach, and new refinements in flap design are presented. The indications for the flap and its role in ablative tumor surgery are discussed. This flap has proved to be versatile, easy to raise, and extremely hardy. The ample skin island with its large arc of rotation is well vascularized, healing well even in irradiated wounds, and the flap tolerates both postoperative pressure and radiation.


Clinicopathological Features of 19 Eyelid Pilomatrixomas.
Pilomatrixoma is a relatively rare, benign tumor arising from the hair root matrix. It is found frequently on the head and neck, with most involving the eyebrow in the periocular region. In contrast, eyelid pilomatrixoma is less common, and often clinically misdiagnosed. Here, we present clinical and histological data from 19 pilomatrixomas arising in the eyelid. The study represents a retrospective study of eyelid pilomatrixoma diagnosed at our institution since 1981. All slides were reviewed, and demographic as well as clinical data were obtained. Patient ages ranged from 2 to 63 years (mean 24 years), including 12 (63%) females and 7 (37%) males. Eight (42%) and 4 (21%) cases arose in the first and second decades of life, respectively. Upper eyelid involvement was found in 14 (74%) of cases. Microscopically, the tumors were characterized by basaloid and shadow cells accompanied by calcification and foreign body giant cells. Eyelid pilomatrixoma is rarely suspected clinically, and can be mistaken for cyst, chalazion, sebaceous carcinoma, and other tumors. Physicians should consider the possibility of pilomatrixoma in the eyelid area, especially in children or young female patients. Complete excision is curative, and diagnosis can generally be established by histopathological examination.


A new desert-dwelling dinosaur (Theropoda, Noasaurinae) from the Cretaceous of south Brazil.
Noasaurines form an enigmatic group of small-bodied predatory theropod dinosaurs known from the Late Cretaceous of Gondwana. They are relatively rare, with notable records in Argentina and Madagascar, and possible remains reported for Brazil, India, and continental Africa. In south-central Brazil, the deposits of the Bauru Basin have yielded a rich tetrapod fauna, which is concentrated in the Bauru Group. The mainly aeolian deposits of the Caiuá Group, on the contrary, bear a scarce fossil record composed only of lizards, turtles, and pterosaurs. Here, we describe the first dinosaur of the Caiuá Group, which also represents the best-preserved theropod of the entire Bauru Basin known to date. The recovered skeletal parts (vertebrae, girdles, limbs, and scarce cranial elements) show that the new taxon was just over 1 m long, with a unique anatomy among theropods. The shafts of its metatarsals II and IV are very lateromedially compressed, as are the blade-like ungual phalanges of the respective digits. This implies that the new taxon could have been functionally monodactyl, with a main central weight-bearing digit, flanked by neighbouring elements positioned very close to digit III or even held free of the ground. Such anatomical adaptation is formerly unrecorded among archosaurs, but has been previously inferred from footprints of the same stratigraphic unit that yielded the new dinosaur. A phylogenetic analysis nests the new taxon within the Noasaurinae clade, which is unresolved because of the multiple alternative positions that Noasaurus leali can acquire in the optimal trees. The exclusion of the latter form results in positioning the new dinosaur as the sister-taxon of the Argentinean Velocisaurus unicus.


Mourning the frozen: considering the relational implications of cryonics.
Cryonics is the preservation of legally dead human bodies at the temperature of liquid nitrogen in the hope that future technologies will be able to revive them. In philosophical debates surrounding this practice, arguments often focus on prudential implications of cryopreservation, or moral arguments on a societal level. In this paper, we claim that this debate is incomplete, since it does not take into account a significant relational concern about cryonics. Specifically, we argue that attention should be paid to the potential implications of cryopreservation for the mourning processes of surviving loved ones. Cryopreservation increases the likelihood of disruption of the practical and mental tasks involved in a successful mourning process, which can negatively impact survivors of the cryopreserved patient. To illustrate my argument, we will draw on a case study from the 2019 documentary Hope Frozen We aim to introduce this concern, in order to gain a more complete view on the potential implications of cryopreservation.


Thrombin generation assay: a new tool to predict and optimize clinical outcome in cardiovascular patients?
Antithrombotic therapy (including antiplatelet and anticoagulant drugs) is the cornerstone of the current medical treatment of patients with acute coronary syndromes (ACS). This therapy and particularly the new antiplatelet and anticoagulant drugs have significantly reduced the ischemic risk, but have increased bleeding complications. Recently, several studies have emphasized the negative prognostic impact on long-term mortality of these bleeding adverse events. Thus, new assays to estimate the bleeding risk and the efficacy of these antithrombotic drugs are clearly in demand. Regarding the anticoagulant drugs, new promising data have emerged about the thrombin generation assay (TGA). TGA measures the ability of plasma to generate thrombin. TGA may be used to check coagulation function, to value risk of thrombosis and to compare the efficacy of different anticoagulants employed in clinical management of patients with ACS. The TGA result is a curve which describes the variation of thrombin's amount during the activation of the coagulation cascade. All available anticoagulant drugs influence the principal parameters generated by TGA and so it is possible to evaluate the effects of the medical treatment. In this review we provide a brief description of the assay and we summarize the principals of previous studies by analyzing the relationship between anticoagulant drugs and TGA. Moreover, a brief summary of its ability to predict ischemic and bleeding risks has been provided.


Horizon ratio bound for inflationary fluctuations.
We demonstrate that the gravity wave background amplitude implies a robust upper bound on the wavelength-to-horizon ratio at the end of inflation: lambda/H(-1) less than or approximately equal e(60), as long as the cosmic energy density does not drop faster than radiation subsequent to inflation. This limit implies that N, the number of e-folds between horizon exit and the end of inflation for wave modes of interest, is less, similar 60 plus a model-dependent factor-for vast classes of slow-roll models, N less than or approximately equal 67. As an example, this bound solidifies the tension between observations of the cosmic microwave background anisotropies and chaotic inflation with a phi(4) potential by closing the escape hatch of large N (<62).


Role of Dynamic Parameters of 18F-DOPA PET/CT in Pediatric Gliomas.
PET with 18F-DOPA can be used to evaluate grading and aggressiveness of pediatric cerebral gliomas. However, standard uptake parameters may underperform in circumscribed lesions and in diffuse pontine gliomas. In this study, we tested whether dynamic 18F-DOPA PET could overcome these limitations. Patients with available dynamic 18F-DOPA PET were included retrospectively. Static parameters (tumor/striatum ratio [T/S] and tumor/cortex ratio [T/N]) and dynamic ones, calculated on the tumor time activity curve (TAC), including time-to-peak (TTP), slope steepness, the ratio between tumor and striatum TAC steepness (dynamic slope ratio [DSR]), and TAC shape (accumulation vs plateau), were evaluated as predictors of high/low grading (HG and LG) and of progression-free survival and overall survival. Fifteen patients were included; T/S, T/N, TTP, TAC slope steepness, and DSR were not significantly different between HG and LG. The accumulation TAC shape was more prevalent in the LG than in the HG group (75% vs 27%). On progression-free survival univariate analysis, TAC accumulation shape predicted longer survival (P < 0.001), whereas T/N and DSR showed borderline significance; on multivariate analyses, only TAC shape was retained (P < 0.01, Harrell C index, 0.93-0.95). On overall survival univariate analysis, T/N (P < 0.05), DSR (P < 0.05), and TAC "accumulating" shape predicted survival (P < 0.001); once more, only this last parameter was retained in the multivariate models (P < 0.05, Harrell C index, 0.86-0.89). Dynamic 18F-DOPA PET analysis outperforms the static parameter evaluation in grading assessment and survival prediction. Evaluation of the curve shape is a simple-to-use parameter with strong predictive power.


Novel Ratiometric Fluorescent Nanothermometers Based on Fluorophores-Labeled Short Single-Stranded DNA.
Novel ratiometric fluorescent short single-stranded DNA (ssDNA) nanothermometers (ssDNA FT) were developed using the fluorescence resonance energy transfer (FRET) effect of the ssDNA's end labeled fluorophores. An optimal ssDNA sequence and associated ssDNA FT were determined through combined MD simulation and temperature-related FRET analysis. Their fluorescence properties and thermo-responsivities were analyzed using fluorescence spectra. The influences of ssDNA' sequence length, sequence composition and fluorescent labels for temperature sensing were investigated. Results revealed the prepared, optimized ssDNA FT showed a high average temperature sensitivity of 7.04% °C1-, wide linear response range of 0-100 °C, and excellent stability with various environmental factors. Furthermore, this ssDNA FT was successfully used for intracellular temperature sensing in cancer cells and was used for in vivo thermos-imaging during microwave hyperthermia of tumor tissue. Advantages in size, sensitivity, and stability proved the feasibility of ssDNA FT in nanoscale thermometry applications, and this novel fluorescent thermometry mechanism is of large potential in the development of FTs. This investigation of ssDNA's molecular thermosensitivity could give rise to a new prospective in the nanothermometry field.


Effectiveness of mist-blower applications of malathion and permethrin to foliage as barrier sprays for salt marsh mosquitoes.
Permethrin and malathion were applied as salt marsh mosquito barrier sprays by mist-blower to the shrub border of a park. At one and 24 h after treatment, mosquito landing counts in both insecticide treated areas declined by 80-90% relative to counts in an untreated control area. After 48 h, in the malathion-treated area, mosquito activity returned to levels observed in the control area. From 2 to 8 days post-treatment, mosquito landing counts in the permethrin-treated area remained depressed and significantly (P less than 0.01) different from the malathion-treated and control areas. On days 9 and 10 post-treatment, mosquito landing rates returned to high levels in the insecticide-treated and control areas.


A naturalistic study of railway controllers.
There is an increasing prevalence for work to be analysed through naturalistic study, especially using ethnographically derived methods of enquiry and qualitative field research. The relatively unexplored domain of railway control (in comparison to signalling) in the UK is described in terms of features derived from observations and semi-structured interviews. In addition, task diagrams (a technique taken from the Applied Cognitive Task Analysis toolkit) are used to represent controllers' core elements of work, i.e. to manage events or incidents, and to identify the challenging steps in the process. The work features identified, the task diagrams, and the steps identified as challenging form a basis from which future ergonomics studies on railway controllers in the UK will be carried out.


Diagnostic Performance of Diffusion-Weighted Imaging for Multiple Hilar and Mediastinal Lymph Nodes with FDG Accumulation.
It is sometimes difficult to assess patients who have multiple hilar and mediastinal lymph nodes (MHMLN) with FDG accumulation in PET-CT. Since it is uncertain whether diffusion-weighted magnetic resonance imaging (DWI) is useful in the assessment of such patients, its diagnostic performance was assessed. Twenty-three patients who had three or more stations of hilar and mediastinal lymph nodes with SUVmax of 3 or more in PET-CT were included in this study. For diagnosis of disease, there were 20 malignancies (lung cancers 17, malignant lymphomas 2 and metastatic lung tumor 1), and 3 benign cases (sarcoidosis 2 and benign disease 1). For diagnosis of lymph nodes, there were 7 malignancies (metastasis of lung cancer 7 and malignant lymphoma 1) and 16 benign lymphadenopathies (pneumoconiosis/silicosis 7, sarcoidosis 4, benign disease 4, and atypical lymphocyte infiltration 1). The ADC value (1.57±0.29x10(-3) mm2/sec) of malignant MHMLN was significantly lower than that (1.99±0.24x10(-3) mm2/sec) of benign MHMLN (P=0.0437). However, the SUVmax was not significantly higher (10.0±7.34 as compared to 6.38±4.31) (P=0.15). The sensitivity (86%) by PET-CT was not significantly higher than that (71%) by DWI for malignant MHMLN (P=1.0). The specificity (100%) by DWI was significantly higher than that (31%) for benign MHMLN (P=0.0098). Furthermore, the accuracy (91%) with DWI was significantly higher than that (48%) with PET-CT for MHMLN (P=0.0129). Evaluation by DWI for patients with MHMLN with FDG accumulation is useful for distinguishing benign from malignant conditions.


Analysis of GHB and 4-methyl-GHB in postmortem matrices after long-term storage.
Postmortem heart blood, peripheral blood, vitreous humor, urine, and bile specimens from 26 autopsy cases were analyzed for the presence of gamma-hydroxybutyric acid (GHB) and gamma-methyl gamma-hydroxybutyric acid (4-Me-GHB) after long-term freezer storage. Cases were selected for which exogenous GHB, gamma-butyrolactone (GBL), gamma valerolactone (GVL), or 1,4-butanediol use was not suspected. One documented positive GHB case subjected to the same storage conditions was also evaluated for comparison. Specimens did not contain any preservatives or additives except heart blood, which contained sodium fluoride (2% w/v). The results of the analysis for GHB in vitreous humor (n = 26) demonstrated, with one exception, concentrations below the limit of detection for the method (5 mg/L). In the exception case, the value was determined to be 7 mg/L. Documented cases of GHB positive fatalities showed vitreous humor concentrations (n = 6) that exceeded this range by a factor of 12 or more. There was no apparent relationship between storage times and GHB concentrations. The data developed in this study demonstrate a postmortem endogenous range for GHB in vitreous humor that is less than or equal to 7 mg/L. Studies of the stored GHB-positive case demonstrated no significant change in concentration over the time period studied. None of the specimens analyzed in this study contained detectable amounts of 4-Me-GHB. This would support the contention that when 4-Me-GHB is detected, it is most likely due to the exogenous consumption of GVL.


Safety and efficacy of physiologist-led dobutamine stress echocardiography: experience from a tertiary cardiac centre
Dobutamine stress echocardiography (DSE) services have traditionally been medically led. In some UK institutions, DSE lists are led by physiologists with medical support. In our tertiary cardiac centre at New Cross Hospital (NCH), the DSE service was established by a consultant echocardiographer. Following intensive training and assessment, the Trust approved drug administration by named senior cardiac physiologists. We believe this is the first report of a cardiac physiologist-managed DSE service, including physiologist drug administration. We have assessed the feasibility, safety and validity of this physiologist-led DSE service. Retrospective analysis of 333 patients undergoing stress echocardiogram for inducible reversible ischaemia, myocardial viability and valvular heart disease over 6 months. Patients' case notes review after 18–24 months. Overall, 92% of all cases (306) were performed by physiologists. In 300 studies, dobutamine was administered. The majority of the referrals were for coronary artery disease (CAD) assessment (281). In 235 cases, the study was uncomplicated. Sixty-seven patients developed dobutamine-related side effects. In 16 cases, complications led to early termination of the study. In two cases, urgent medical review was needed. Of the 281 studies for CAD assessment, 239 were negative for ischaemia, 28 were positive and 14 inconclusive. In 5 out of 28 cases with echocardiogram, evidence of inducible ischaemia, coronary angiography revealed unobstructed coronary arteries. This study demonstrates the safety and effectiveness of this practice and provides potential for the expansion of the physiologists' role and physiologist-led DSE services in other hospitals.


Virucidal hand treatments for prevention of rhinovirus infection.
Rhinovirus infections are associated with substantial morbidity and economic cost. The available common cold remedies are of limited utility and specific antiviral approaches have been unsuccessful. Viral contamination of the hands appears to play an important role in the transmission of rhinovirus from person-to-person. Interruption of this step in transmission presents a potential target for intervention. Initial studies demonstrated that the common cold could be prevented by treatment of hands with iodine. Inactivation of the rhinoviruses by acid is well known and a survey of organic acids considered safe for consumer use revealed that salicylic acid and pyroglutamic acid have potent virucidal activity for the rhinoviruses that persists for several hours after application to the hands. A subsequent evaluation in human volunteers confirmed the prevention of rhinovirus infections by these acids and suggested that these agents have promise as cosmetically acceptable virucidal agents for interruption of the transmission of these infections.


Dynamics of polymers in a particle-based mesoscopic solvent.
We study the dynamics of flexible polymer chains in solution by combining multiparticle-collision dynamics (MPCD), a mesoscale simulation method, and molecular-dynamics simulations. Polymers with and without excluded-volume interactions are considered. With an appropriate choice of the collision time step for the MPCD solvent, hydrodynamic interactions build up properly. For the center-of-mass diffusion coefficient, scaling with respect to polymer length is found to hold already for rather short chains. The center-of-mass velocity autocorrelation function displays a long-time tail which decays algebraically as (Dt)(-3/2) as a function of time t, where D is the diffusion coefficient. The analysis of the intramolecular dynamics in terms of Rouse modes yields excellent agreement between simulation data and results of the Zimm model for the mode-number dependence of the mode-amplitude correlation functions.


mGlu1 receptor canonical signaling pathway contributes to the opening of the orphan GluD2 receptor.
The orphan Glutamate receptor Delta2 (GluD2) intrinsic ion channel activity is indirectly triggered by glutamate through stimulation of the metabotropic glutamate receptor 1 (mGlu1), in cerebellar Purkinje cells. However, the mechanisms of GluD2 ion channel opening are entirely unknown. In this work, we investigated the signaling pathways underlying the mGlu1-induced GluD2 current, performing whole-cell voltage-clamp recordings from mGlu1 and GluD2 transfected HEK293 cells. We show that the activation of GluD2 channels via DHPG-induced mGlu1 stimulation is Gαq-dependent. Moreover, inhibition of the downstream components of the mGlu1 canonical signaling pathway PLC and PKC with U73122 and GF109203X, respectively, strongly reduced the DHPG-induced GluD2 current. These results were further confirmed on endogenous receptors at the Parallel Fiber - Purkinje Cell cerebellar synapse, indicating that the opening of the GluD2 channel by mGlu1 receptor mobilizes the canonical Gq-PLC-PKC pathway. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.


Nd:YAG capsulotomy rates after use of the AcrySof acrylic three piece and one piece intraocular lenses.
Acrylic lens size and shape may influence the rate of posterior capsule opacification (PCO) and need for Nd:YAG capsulotomy. The aim of this study is to compare the Nd:YAG capsulotomy rate of the three piece acrylic/PMMA AcrySof MA series lens with the one piece acrylic AcrySof SA series lens. 434 eyes of 329 patients who had cataract extraction and implantation of one of four types of intraocular lenses (IOLs) were evaluated for rate of Nd:YAG capsulotomy. 176 eyes received the acrylic AcrySof MA30AC IOL, 71 eyes the acrylic AcrySof MA60AC IOL, 45 eyes the acrylic AcrySof SA30AL IOL, and 142 eyes the acrylic AcrySof SA60AT IOL. The rates of Nd:YAG capsulotomy with the three piece IOL (MA30AC/MA60AC) and the one piece IOL (SA30AL/SA60AT) were 1.2% and 2.1% at 6 months, 2.8% and 5.9% at 12 months, and 3.6% and 7.5% at 24 months, respectively. The incidence of Nd:YAG capsulotomy was higher in patients who received the one piece IOL (p=0.01, log rank test). There was no difference in Nd:YAG capsulotomy rates when comparing lens optic size, age, sex, history of pars plana vitrectomy, and diabetes mellitus. This study shows a greater incidence of Nd:YAG capsulotomy in patients who receive one piece acrylic AcrySof lenses when compared to those who receive three piece acrylic AcrySof lenses.


Evaluation of sustainable e-waste collection method for urban and rural region of India.
Electronic waste is one of the most challenging waste streams to manage. It has become a significant concern in developing countries due to the ever-increasing volume of generation coupled with deficient growth in collection and processing infrastructure. For the various stakeholders, it is of paramount importance to adopt a robust and sustainable collection method for hazard mitigation. The prevalent e-waste collection methods are categorized under four major heads, namely take-back, retail store, door-to-door and curbside collection. The e-waste collection problems are analysed from various perspective, based on literature that cited developing country-specific survey and data that includes India. Economic sustainability and potential risk are included as attributes in the evaluation scheme. We attempt to establish a decision-making model. Discussion with the field experts and decision-makers (DMs) provided the weights for various attributes and sub-attributes. A fuzzy linguistic scale is used to take care of ambiguity in DMs' opinion. Fuzzy- Analytical Hierarchy Process (FAHP) is used to determine the importance of various attributes and sub-attributes, while Fuzzy-VlseKriterijumska Optimizacija I Kompromisno Resenje (FVIKOR) is used to determine the rank of the alternatives. Based on the analysis, 'take-back collection' and 'retail store based collection' are found the most suitable options for urban and rural regions respectively. The attributes, social awareness and economical sustainability are found to have the highest significance in both cases. Implementation of a collection method is an expensive activity, and the proposed Fuzzy-Multi Attribute Decision Making attempts to capture various attributes and their complex interplay to arrive at a decision on optimum e-waste collection option(s) in a specific locality.


Structural study of DNA condensation induced by novel phosphorylcholine-based copolymers for gene delivery and relevance to DNA protection.
Poly[2-(dimethylamino)ethyl methacrylate-b-2-methacryloyloxyethyl phosphorylcholine] (DMA-MPC) is currently under investigation as a new vector candidate for gene therapy. The DMA block has been previously demonstrated to condense DNA effectively. The MPC block contains a phosphorylcholine (PC) headgroup, which can be found naturally in the outside of the cell membrane. This PC-based polymer is extremely hydrophilic and acts as a biocompatible steric stabilizer. In this study, we assess in detail the morphologies of DNA complexes obtained using the diblock copolymer series DMA(x)MPC30 (where the mean degree of polymerization of the MPC block was fixed at 30 and the DMA block length was systematically varied) using transmission electron microscopy (TEM) and liquid atomic force microscopy (AFM). Both techniques indicate more compact complex morphologies (more efficient condensation) as the length of the cationic DMA block increases. However, the detailed morphologies of the DMA(x)MPC30-DNA complexes observed by TEM in vacuo and by AFM in aqueous medium are different. This phenomena is believed to be related to the highly hydrophilic nature of the MPC block. TEM studies revealed that the morphology of the complexes changes from loosely condensed structures to highly condensed rods, toroids, and oval-shaped particles as the DMA moiety increases. In contrast, morphological changes from plectonemic loops to flower-like and rectangular block-like structures, with an increase in highly condensed central regions, are observed by in situ AFM studies. The relative population of each structure is clearly dependent on the polymer molecular composition. Enzymatic degradation assays revealed that only the DMA homopolymer provided effective DNA protection against DNase I degradation, while other highly condensed copolymer complexes, as judged from TEM and gel electrophoresis, only partially protected the DNA. However, AFM images indicated that the same highly condensed complexes have less condensed regions, which we believe to be the initiation sites for enzymatic attack. This indicates that the open structures observed by AFM of the DNA complexation by the DMA(x)MPC30 copolymer series are closer to in vivo morphology when compared to TEM.


MICAgen Mice Recapitulate the Highly Restricted but Activation-Inducible Expression of the Paradigmatic Human NKG2D Ligand MICA.
NKG2D is a potent activating immunoreceptor expressed on nearly all cytotoxic lymphocytes promoting their cytotoxicity against self-cells expressing NKG2D ligands (NKG2DLs). NKG2DLs are MHC class I-like glycoproteins that usually are not expressed on "healthy" cells. Rather, their surface expression is induced by various forms of cellular stress, viral infection, or malignant transformation. Hence, cell surface NKG2DLs mark "dangerous" cells for elimination by cytotoxic lymphocytes and therefore can be considered as "kill-me" signals. In addition, NKG2DLs are up-regulated on activated leukocytes, which facilitates containment of immune responses. While the NKG2D receptor is conserved among mammals, NKG2DL genes have rapidly diversified during mammalian speciation, likely due to strong selective pressures exerted by species-specific pathogens. Consequently, NKG2DL genes are not conserved in man and mice, although their NKG2D-binding domains maintained structural homology. Human NKG2DLs comprise two members of the MIC (MICA/MICB) and six members of the ULBP family of glycoproteins (ULBP1-6) with MICA representing the best-studied human NKG2DLs by far. Many of these studies implicate a role of MICA in various malignant, infectious, or autoimmune diseases. However, conclusions from these studies often were limited in default of supporting in vivo experiments. Here, we report a MICA transgenic (MICAgen) mouse model that replicates central features of human MICA expression and function and, therefore, constitutes a novel tool to critically assess and extend conclusions from previous in vitro studies on MICA. Similarly to humans, MICA transcripts are broadly present in organs of MICAgen mice, while MICA glycoproteins are barely detectable. Upon activation, hematopoietic cells up-regulate and proteolytically shed surface MICA. Shed soluble MICA (sMICA) is also present in plasma of MICAgen mice but affects neither surface NKG2D expression of circulating NK cells nor their functional recognition of MICA-expressing tumor cells. Accordingly, MICAgen mice also show a delayed growth of MICA-expressing B16F10 tumors, not accompanied by an emergence of MICA-specific antibodies. Such immunotolerance for the xenoantigen MICA ideally suits MICAgen mice for anti-MICA-based immunotherapies. Altogether, MICAgen mice represent a valuable model to study regulation, function, disease relevance, and therapeutic targeting of MICA in vivo.


A Life-Long Approach to Physical Activity for Brain Health.
It is well established that engaging in lifelong Physical activity (PA) can help delay the onset of many chronic lifestyle related and non-communicable diseases such as cardiovascular disease, type two diabetes, cancer and chronic respiratory diseases. Additionally, growing evidence also documents the importance of PA for brain health, with numerous studies indicating regular engagement in physical activities may be protective against cognitive decline and dementia in late life. Indeed, the link between PA and brain health may be different at each stage of life from childhood, mid-life and late life. Building on this emerging body of multidisciplinary research, this review aims to summarize the current body of evidence linking regular PA and brain health across the lifespan. Specifically, we will focus on the relationship between PA and brain health at three distinct stages of life: childhood and adolescence, mid-life, late life in cognitively healthy adults and later life in adults living with age-related neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD).


Immunochemical identification of the chick HPRT gene transferred from chick erythrocytes to mammalian somatic cells.
Immunochemical methods were used to identify the genetic origin of hypoxanthine phosphoribosyltransferase (HPRT) expressed in heteroploid, HPRT-deficient mouse (A9) cells and Chinese hamster ovary (K627) cells, after these cells were fused with chick embryo erythrocytes and selected for resistance to hypoxanthine-aminopterin-thymidine (HAT) medium. All of the HAT-selected clones produced HPRT activity which was immunoprecipitable by an antiserum specific for chick HPRT, but not by an antiserum specific for mouse and hamster HPRT. Furthermore, the HPRT activity in these clones was electrophoretically indistinguishable from chick liver HPRT and clearly different from mouse liver HPRT. These data provide evidence that the HPRT activity expressed in cell hybrids produced by the fusion of HPRT-negative mammalian cells and chick erythrocytes containing genetically inactive nuclei is indeed coded by the chick HPRT gene and that an avian gene can be stably incorporated and correctly expressed in a mammalian cells.


Synthesis and aqueous aggregation properties of amphiphilic surface-block dendrimers.
[reaction: see text] A family of dendritic amphiphiles were synthesized from the natural metabolites of glycerol, succinic acid, and myristic acid. The surfaces of these dendrimers display different numbers of alkyl chains and carboxylic acids, varying the hydrophobic-to-hydrophilic ratio over a relatively broad range. In solution these dendritic amphiphiles form supramolecular structures, and these aggregates have been characterized by light microscopy, transmission electron microscopy, and tensiometry. These aggregates can entrap the hydrophobic species pyrene.


Fumigation characteristics of ozone in postharvest treatment of Kabkab dates (Phoenix dactylifera L.) against selected insect infestation.
Methyl bromide fumigation, the most accepted quarantine treatment for dates and many other dried commodities, will be phased out by 2015 worldwide. As a result, there is a critical need to develop durable alternatives for methyl bromide as postharvest treatments of agricultural commodities. This article presents a new method for postharvest treatment of Kabkab dates (Phoenix dactylifera L.) by application of gaseous ozone to reduce or eliminate all life stages (adults, larvae, and eggs) of Indian meal moth (Plodia interpunctella) and sawtooth grain beetle (Oryzaephilus surinamensis). The effect of the ozonation process on the sugar content of dates was also evaluated. Infested dates were exposed to ozone concentrations of 600, 1,200, 2,000, and 4,000 ppm for 1 and 2 h. As insect eggs are known to be most tolerant to many chemical or physical treatments, they were additionally exposed to an atmosphere of pure carbon dioxide prior to ozonation. Exposing samples to ozone concentrations of >2,000 ppm for 2 h resulted in complete mortality of larvae and adults. Exposure to 4,000 ppm of ozone for 2 h resulted in 80% mortality of eggs, and exposure to CO(2) prior to ozonation did not improve the effect of ozonation on eggs. Ozone did not have any influence on the sugar content of Kabkab dates.


Value-Based Insurance Design Pharmacy Benefits for Children and Youth With Special Health Care Needs: Principles and Opportunities.
Value-based insurance design (VBID) represents an innovative approach to health insurance coverage. In the context of pharmacy benefits, the goal of VBID is to minimize access barriers to the most effective and appropriate treatments for specific medical conditions. Both private and public insurance programs have explored VBID pharmacy projects primarily for medical conditions affecting adults. To date, evidence for VBID pharmacy programs for children and youth with special health care needs (CYSHCN) appears lacking. There appears to be potential for VBID concepts to be applied to pharmacy coverage benefiting CYSHCN. An overview of VBID pharmacy principles and guiding principles are presented. Opportunities for the creation of pharmacy programs with a value-based orientation and challenges to the redesign of pharmacy benefits are identified. VBID pharmacy coverage principles may be helpful to improve medication use and important clinical outcomes while lowering barriers to medication use for the population of CYSHCN. Pilot projects of VBID pharmacy benefits for children and youth should be explored. However, many questions remain.


A misleading implication of the metabolism scans of the brain.
Metabolism scans of the brain measure the quantity of energy consumed by parts of the brain while performing a cognitive task. This quantity of energy is wrongly considered to represent the amount of data processing by the related parts of the brain. Thus, a misleading conception of the relative parts of the cerebral hemispheres in performing cognitive tasks is created.


The Recovery Strengths Questionnaire for alcohol and drug use disorders.
The Recovery Strengths Questionnaire (RSQ) is a 15-item self-report questionnaire that assesses an addicted individual's recovery strengths. This study aimed to validate the RSQ as a measure of recovery capital. As part of a larger study, 151 participants in addiction recovery groups from across the UK completed the RSQ. Participants also completed the Assessment of Recovery Capital questionnaire and provided some demographic information. The RSQ was found to be psychometrically sound, with high internal consistency and concurrent validity with the Assessment of Recovery Capital. RSQ scores were positively correlated with length of time in recovery and length of membership in recovery groups, and the scores could be used to discriminate between those in early and late recovery. Principal components analysis revealed a two-factor structure of recovery capital. These two factors were named 'within-group recovery strengths' and 'externally generated recovery strengths', and it was found that only the within-group factor scale (i.e. resources developed within recovery groups) predicted length of time in recovery and recovery groups. These results highlight the important role that recovery groups can play in an individual's recovery, and they provide an alternative factor structure to the one-factor structure of the Assessment of Recovery Capital.


Bilateral Asymmetries Assessment in Elite and Sub-Elite Male Futsal Players.
This study aimed to investigate morphological, functional, and neuromuscular asymmetries on futsal players' lower limbs at different competitive levels. Sixteen male elite futsal players from the Spanish National Futsal League and thirteen male sub-elite futsal players from the third division participated in this study. Morphological asymmetry was assessed through bioelectrical impedance (fat-mass (g and %) and lean-mass (g)). Functional asymmetry was assessed by means of a 20-second static unipedal balance test. Finally, neuromuscular asymmetry was assessed using tensiomiography tests on both the rectus femoris (RF) and biceps femoris (BF) of each participant. The three tests conducted did not reveal significant bilateral asymmetries in elite players. On the other hand, sub-elite players showed significant bilateral asymmetry in fat-mass percentage between dominant and non-dominant limbs (+6%; CI95%: 1 to 11; ES: 0.88; p = 0.019). They also showed higher bilateral asymmetry in the delay time of the RF (+13%; CI95%: 7 to 21; ES: 1.3; p < 0.05). However, the static unipedal balance test (p > 0.05) did not evidence asymmetries regardless of the level of the participants. Elite futsal players do not develop bilateral asymmetries in lower limbs in the studied parameters. On the contrary, sub-elite players are likely to develop morphological and neuromuscular asymmetries between their dominant leg and non-dominant leg.


Simply Constructed and Highly Efficient Classified Cargo-Discharge DNA Robot: A DNA Walking Nanomachine Platform for Ultrasensitive Multiplexed Sensing.
In this work, a classified cargo-discharge DNA robot with only two DNA strands was designed and driven by an analogous proximity ligation assay (aPLA)-based enzyme cleaving for fast walk to construct a novel electrochemical biosensor for simultaneously ultrasensitive detection of microRNA-155 (miRNA-155) and miRNA-21. Compared with traditional DNA nanomachines, the multifunctional DNA robot possessed simple structure, high self-assembling efficiency and walking efficiency. Once it interacted with target miRNAs, this DNA robot could walk fast on the electrode surface and realize the classified cargoes discharging including beacons methylene blue (MB) and ferrocene (Fc), respectively labeled in the double-stranded DNA (A1-A2) for ultrasensitive detection of multiple miRNAs simultaneously. As a result, the wide linearity ranging from 100 aM to 100 pM and low detection limits of 42.7 and 51.1 aM were obtained for miRNA-155 and miRNA-21 detection, respectively. As a proof of concept, the present strategy initiates a novel and highly efficient walking platform to realize the ultrasensitive detection of biomarkers and possesses potential applications in the clinical diagnosis of disease.


Foot deformities in children with cerebral palsy.
The present article describes common foot deformities in children with cerebral palsy and discusses treatment options for each of those deformities. Bracing is a useful treatment to correct foot deformities during gait. Surgical correction of foot deformities is typically performed as a part of multilevel single-event gait improvement surgery that has increasingly become the standard of care for ambulatory children with cerebral palsy. Foot realignment may improve knee function during stance, probably because of change of lever arm. Foot deformities are common among children with cerebral palsy. The three most common among them are equinus, planovalgus and equinovarus/equinocavovarus. Treatment consists of orthotics, physical therapy, spasticity reduction treatment and surgical correction. Guidelines for treatment are individualized and multifactorial. Important considerations include the child's level of function, the severity and flexibility of the deformity, the presence or absence of pain and skin irritation, and the changes in alignment observed over time.


Disruption of the blood-brain barrier in Parkinson's disease: curse or route to a cure?
The vertebrate blood-brain barrier (BBB) is critical for ensuring the maintenance of brain homeostasis, whilst protecting the brain against toxic insults. Various pathological events disrupt BBB integrity, holding several important clinical implications. In instances where the normal mechanisms controlling passage of substances into the brain are compromised, these could sensitize or even worsen endogenous pathological conditions. Recognition has grown recently that patients diagnosed with Parkinson's disease (PD) present with concurrent medical problems, including cerebrovascular lesions. However, cerebrovascular disturbances may also result from PD-related disease processes; the pathological mechanisms which could entail interaction between environment-derived and genetic factors. The current review addresses the accumulation of studies aimed at better understanding the series of processes affecting the neurovascular unit in human Parkinsonism, due in part to the BBB presenting as a formidable opponent in the effective delivery of therapeutics that have shown promise as therapeutic strategies for treating aspects of PD when tested in vitro.


Changing pace: Using implementation intentions to enhance social distancing behavior during the COVID-19 pandemic.
Since the first case of COVID-19 in the U.S. on January 20, 2020, the disease caused by the new strain of coronavirus has spread exponentially across the country. While the spread of this disease can be significantly slowed if people practice "social distancing," it is difficult to break old habits and acquire new behaviors at the needed speed. The purpose of this study is to challenge how health risk messages are currently communicated (specifically by considering how the Center of Disease Control (CDC) communicates its recommendations for social distancing) and suggest an alternative way. We tested and applied the use of a robust behavioral intervention known as "if-then" plans (plans that spell out in advance how one wants to achieve a goal they have previously set) to encourage the acquisition of a new behavior (e.g., social distancing) during this time of crisis. Using a longitudinal mixed design (within-/between-subjects study) daily diary study, we hypothesized and observed (via multilevel modeling) that those randomized into the experimental group (those who created and practiced if-then plans) demonstrated increased social distancing over time, whereas engagement in social distancing did not change in the control condition (those who observed the CDC guidelines). These results were sustained in a 3-week follow-up examination for those who were strongly committed to the goal to social distance. Such evidence suggests that risk communication messaging that includes if-then plans is an effective way of acquiring new behaviors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Prevalence of positive skin test responses to 53 allergens in patients with rhinitis symptoms.
Prior studies looking at allergic sensitization have focused on narrow age ranges or small numbers of allergens. This study is the first to examine the prevalence of positive skin test responses in a symptomatic military population with a wide age range of patients and large number of allergens. This study was a retrospective analysis of our skin test database. We included 1137 patients aged 4-79 years old who underwent our standard skin-prick testing panel of 53 aeroallergens and 2 controls using the Quintest device (Hollister-Stier, Spokane, WA). Results indicated that 81.6% of patients had at least one positive skin test. Rates of atopy were similar between male and female patients; 9.2% of patients were monosensitized. The average number of positive skin tests peaked in the 10- to 19-year age group at 13.1 and declined in older age groups. The prevalence of atopy peaked in the 30- to 39-year age group at 85.5% and decreased in older age groups. The most common allergens were grasses, mountain cedar, and dust mites. Sensitization rates for many underreported allergens, including mouse and rat, are presented. This study shows that 81.6% of patients in a symptomatic military population were atopic. These rates are high, even when compared with other allergic populations. Atopy peaked in young adulthood and declined in older age groups. Grasses, mountain cedar, and dust mites were the most common allergens. Although performed in a military population, these results should be applicable to many allergy practices.


1-(2-Hydroxy-4,6-dimethylphenyl)ethanone.
In the crystal of the title compound, C(10)H(12)O(2), there are two symmetry-independent molecules, which are essentially superimposable. Each molecule exhibits an intramolecular O-H.O hydrogen bond, with O.O separations of 2.483 (4) and 2.468 (4) A.


Tobacco smoking and periodontal health in a Saudi Arabian population.
Tobacco smoking exerts a harmful effect on the periodontal tissues manifested by periodontal pockets, attachment loss and periodontal bone loss. Current evidences on the effects of tobacco on periodontal health mainly concern cigarette smoking. In view of the increasing popularity of water pipe smoking in Arabian countries and reports confirming that water pipe smoking has health effects similar to those of cigarette smoking, there is a need for a better understanding of the potential harm of this smoking habit. The present thesis was carried out in order to explore whether water pipe smoking is associated with periodontal health in a manner similar to cigarette smoking. Residents in Jeddah City, Saudi Arabia, were invited to participate in the study by means of announcements in two daily newspapers. 355 individuals, 100 women and 255 men (17-60 years) responded to a standardized questionnaire and digital panoramic dental radiographs were taken. The questionnaire included information about oral hygiene practices, dental care and smoking habits. Of these subjects, 262 (73%) also volunteered for clinical examination, including assessments of oral hygiene, gingival inflammation and probing depth. Subgingival microbial test was carried out in 198 individuals for the detection of 12 different bacterial species most commonly associated with periodontal disease using the checkerboard DNA-DNA hybridization technique. Participants were stratified into water pipe smokers 33%, cigarette smokers 20%, smokers of both water pipe and cigarettes (mixed smokers 19%) and non-smokers 28%. Tobacco smoking is associated with a suppression of the gingival bleeding response to plaque accumulation. A suppressive effect was observed in both cigarette and water pipe smokers compared to non-smokers (Study I). Both cigarette and water pipe smoking were associated with the presence of more than 10 pockets of > or = 5 mm probing depth. The relative risk for periodontal disease was 5.1-fold and 3.8-fold increased in water pipe and cigarette smokers, respectively, compared to non-smokers (p < 0.01). The relative risk associated with heavy smoking was about 8-fold elevated in water pipe smokers and 5-fold elevated in cigarette smokers, suggesting an exposure-response effect (Study II). Tobacco smoking was associated with a reduction of the periodontal bone height. The reduction was of similar magnitude in water pipe smokers and cigarette smokers. The relative risk of periodontal bone loss of more than 30% of the root length was 3.5-fold and 4.3-fold elevated in water pipe and cigarette smokers, respectively, compared to non-smokers (p < 0.01). The relative risk associated with heavy smoking was 7.5-fold elevated in water pipe smokers and 6.3-fold elevated cigarette smokers (Study III). Further more, cigarette smokers, water pipe smokers and non-smokers exhibited similar periodontal microflora (Study IV). Tobacco smoking is associated with inferior periodontal health. The impact of water pipe smoking is of largely the same magnitude as that of cigarette smoking. The association between tobacco smoking and an inferior periodontal health seems to be independent of the subgingival microflora. Water pipe smoking habit should be considered in periodontal health.


Clinical application of surface plasmon resonance-based biosensors for fetal fibronectin detection.
Preterm birth is the leading cause of perinatal morbidity and mortality. Fetal fibronectin (fFN), a glycoprotein in the extracellular matrix of the amniotic membranes, is the most powerful biomarker for predicting the risk of preterm birth. Biosensors using the surface plasmon resonance (SPR) response are potentially useful in quantitatively measuring molecules. We established a standard calibration curve of SPR intensity against fFN concentration and used the SPR-based biosensor to detect fFN concentrations in the cervicovaginal secretions of pregnant women between 22 and 34 weeks of gestation. The calibration curve extends from 0.5 ng/mL to 100 ng/mL with an excellent correlation (R(2) = 0.985) based on standard fFN samples. A cutoff value of 50 ng/mL fFN concentration in commercial ELISA kits corresponds to a relative intensity of 17 arbitrary units (a.u.) in SPR. Thirty-two pregnant women were analyzed in our study. In 11 women, the SPR relative intensity was greater than or equal to 17 a.u., and in 21 women, the SPR relative intensity was less than 17 a.u. There were significant differences between the two groups in regular uterine contractions (p = 0.040), hospitalization for tocolysis (p = 0.049), and delivery weeks (p = 0.043). Our prospective study concluded that SPR-based biosensors can quantitatively measure fFN concentrations. These results reveal the potential utility of SPR-based biosensors in predicting the risk of preterm birth.


Prevalence of dental caries in obese and normal-weight Brazilian adolescents attending state and private schools.
To measure the association between dental caries and obesity in adolescents aged 12 to 15 years attending state and private schools. Cross-sectional study. State and private schools in the state of Paraiba, Brazil. 1665 obese and 1665 normal-weight adolescents. These were chosen by means of an anthropometric study using height/age and weight/height indices, adopting as baseline the National Center for Health Statistics indices. The diagnostic criteria for caries were those of the World Health Organization (1997). The average DMFT for obese adolescents from state schools was 4.27 and for those of normal weight it was 4.25 (p = 0.7802). In private schools, the corresponding figures were 1.90 and 1.91, respectively (p = 0.1151). In state schools, the caries prevalence amongst the obese group was 50.9% and amongst those of normal weight, 52.4% (p = 0.5393). In private schools, it was 9.0% amongst the obese group and 9.6% amongst those of normal weight (p 0.6790). There was no statistically significant association between dental caries and obesity. Caries levels were higher amongst adolescents attending state schools.


Self-assembly of fullerene C60-based amphiphiles in solutions.
Fullerene C60 is an all-carbon cage molecule with rich physicochemical properties. It is highly symmetric and hydrophobic, which can be used as a building block for the preparation of amphiphiles that self-assemble into diverse supramolecular structures in aqueous solutions. Meanwhile, C60 is also lipophobic, which is different from the alkyl chains in traditional surfactants. By attaching alkyl chains to the C60 sphere, a new type of lipophobic-lipophilic amphiphiles can be constructed which undergo self-assembly in n-alkanes. When inorganic clusters such as polyoxometalate are linked to the C60 sphere, organic-inorganic hybrids will be obtained which can self-assemble in polar organic solvents. Pristine C60 has also been modified by polar groups such as hydroxy and carboxy, which are linked to hydrophobic moieties and form a new class of amphiphiles. In this review, the self-assembly of C60-based amphiphiles in aqueous and nonaqueous solutions will be summarized. The characteristics exhibited by C60-based amphiphiles during the self-assembly will be discussed with close comparison to traditional surfactants, and the influences of the aggregate formation on the physicochemical properties of the C60 sphere will be described. Finally, a brief summary will be given together with a promising perspective in near future.


Cultural implications for nursing care of the Amish.
The Amish are a conservative Protestant religious sect with a unique set of culture and traditions. In order to provide culturally appropriate and sensitive health care, it is imperative for nurses and other health care providers to have a basic understanding of variations of Amish lifestyle from other cultural groups. Application of Giger and Davidhizar's Transcultural Assessment Model provides information and nursing implications to assist nurses and other health care personnel when caring for Amish clients.


The Emergence of Phenolic Glycans as Virulence Factors in Mycobacterium tuberculosis.
Tuberculosis is the leading infectious cause of mortality worldwide. The global epidemic, caused by Mycobacterium tuberculosis, has prompted renewed interest in the development of novel vaccines for disease prevention and control. The cell envelope of M. tuberculosis is decorated with an assortment of glycan structures, including glycolipids, that are involved in disease pathogenesis. Phenolic glycolipids and the structurally related para-hydroxybenzoic acid derivatives display potent immunomodulatory activities and have particular relevance for both understanding the interaction of the bacterium with the host immune system and also in the design of new vaccine and therapeutic candidates. Interest in glycobiology has grown exponentially over the past decade, with advancements paving the way for effective carbohydrate based vaccines. This review highlights recent advances in our understanding of phenolic glycans, including their biosynthesis and role as virulence factors in M. tuberculosis. Recent chemical synthesis approaches and biochemical analysis of synthetic glycans and their conjugates have led to fundamental insights into their roles in host-pathogen interactions. The applications of these synthetic glycans as potential vaccine candidates are discussed.


Clinical aspects of multinodular pulmonary fibrosis in two warmblood horses.
Two warmblood horses with a history of chronic weight loss and inappetence were referred to the Faculty of Veterinary Medicine, Ludwig-Maximilians University of Munich, Germany, for further examination. The clinical signs in horse 1 were fever, tachycardia and tachypnoea, and chronic ulcerative keratopathy of both eyes. Horse 2 had severe oral ulcerations and was coughing during feeding. In both horses, increased bronchovesicular sounds were heard during auscultation of the lungs. Laboratory findings included mild anaemia, lymphopenia and hypoalbuminaemia. Radiographic examination of the thorax revealed a severe nodular interstitial pattern. Multiple nodular lesions on the surface of the lung were observed by ultrasonographic examination. Light microscopy of lung biopsy specimens obtained from horse 1 revealed a severe chronic fibrosing interstitial pneumonia. Both horses were eventually euthanased because of a poor prognosis. Postmortem examination confirmed severe multinodular fibrosing interstitial pneumonia in both horses, and lung tissue yielded positive results for equine herpesvirus type 5 DNA using PCR assay. On the basis of the clinical, radiographic and pathological findings, as well as the PCR results, the diagnosis of equine multinodular pulmonary fibrosis was established.


[Biologic dosage: its use in high irradiation].
It is impossible, in high-dose irradiation, using only one physical dosimeter, to get any valid information to quantify biological damage to subjects, even if it's possible to measure skin-dose with great accuracy. Radiosensibility changes from one subject to another, thus it's necessary to consider some specific biological parameters to evaluate physical conditions of treated patients. Hematological, genetic and chemical tests are valid means to determine the internally distributed dose and to choose the most appropriate therapeutic "protocol".


Grand Challenges and Future Opportunities for Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) allow compositional and structural diversity beyond conventional solid-state materials. Continued interest in the field is justified by potential applications of exceptional breadth, ranging from gas storage and separation, which takes advantage of the inherent pores and their volume, to electronic applications, which requires precise control of electronic structure. In this Outlook we present some of the pertinent challenges that MOFs face in their conventional implementations, as well as opportunities in less traditional areas. Here the aim is to discuss select design concepts and future research goals that emphasize nuances relevant to this class of materials as a whole. Particular emphasis is placed on synthetic aspects, as they influence the potential for MOFs in gas separation, electrical conductivity, and catalytic applications.


Multireference Electronic Structures of Fe-Pyridine(diimine) Complexes over Multiple Oxidation States.
Noninnocent (redox-active) ligands are increasingly exploited in the design of coordination compounds of earth-abundant transition metals having interesting reactive and catalytic activities. Particular examples of such ligands include those in the pyridine(diimine) (also referred to as bis(imino)pyridine) family. The electronic structures of these compounds are characterized by significant complexity, such that routine single-reference methodologies, for example, Kohn-Sham density functional theory, may be challenged to describe them physically, that is, with quantitatively accurate descriptions of geometries, charge distributions, and spin-state energy separations. We report here RASSCF/RASPT2 calculations on iron pyridine(diimine) complexes over three formal oxidation states that illustrate the highly multiconfigurational characters of these compounds in general and that also offer insights into their electronic ground states and charge distributions.


Analysis of cranial 133-Xenon clearance in the newborn infant by the two-compartment model.
Cranial and chest clearance curves after intravenous administration of 133-Xenon was obtained on 112 occasions in 62 newborn infants admitted to our neonatal intensive care unit. The mean postnatal age was 5.1 days. The cranial clearance curves were submitted to two-compartment analysis. The compartmental clearance rate constants were 1.49 +/- 0.61/min and 0.099 +/- 0.033/min respectively while the fractional flow to the fast compartment was 0.51 +/- 0.14. Possible artefacts, particularly relevant to newborns, were analysed by computer simulation. It is concluded that the cranial 133-Xenon clearance curves varied considerably within the group of ill newborns and that the mean two-compartment parameter values differed considerably from those of healthy premature infants or adults, with or without cerebral illness. But the computer simulations demonstrated that the two-compartment parameters had high coefficients of variation and were significantly biased by right-to-left shunting of blood through the foramen ovale, by heterogeneity of the flow to the fastest compartment and by contamination of the cranial clearance curves by 133-Xenon in the airways. The radiation dose was 1.3 mGy to the lungs and 0.2 mGy to other tissues.


Measuring rates of structural and functional change in glaucoma.
Glaucoma is a progressive optic neuropathy. Hence, most glaucomatous eyes demonstrate signs of deterioration over time despite what may appear to be adequate treatment. The main goal of glaucoma treatment is to slow the rate of disease so that patients can prolong their functional vision. Therefore, it is important for clinicians caring for patients with glaucoma to be able to estimate rates of change with structural and functional outcomes in their patients. Various trend analysis models have been previously used to estimate rates of decay in glaucoma. The authors discuss the relevant issues and the inherent caveats related to estimating structural and functional rates of change in glaucoma. Patterns of deterioration, testing frequency, and combing structural and functional rates of change are also addressed.


Gangliosides and hearing.
Severe auditory impairment observed in GM3 synthase-deficient mice and humans indicates that glycosphingolipids, especially sialic-acid containing gangliosides, are indispensable for hearing. Gangliosides associate with glycoproteins to form membrane microdomains, the composition of which plays a special role in maintaining the structural and functional integrity of hair cells. These microdomains, also called lipid rafts, connect with intracellular signaling and cytoskeletal systems to link cellular responses to environmental cues. During development, ganglioside species are expressed in distinctive spatial and temporal patterns throughout the cochlea. In both mice and humans, blocking particular steps of ganglioside metabolism produces distinctive neurological and auditory phenotypes. Thus each ganglioside species may have specific, non-overlapping functions within the cochlea, central auditory network, and brain.


Insights into arsenic multi-operons expression and resistance mechanisms in Rhodopseudomonas palustris CGA009.
Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III)) concentrations (up to 1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase (55 h). ars2 operon was actively expressed even at the low concentration of As(III) (0.01 μM), whereas the ars3 operon was expressed at 1.0 μM of As(III), indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase). Arsenic speciation analysis demonstrated that R. palustris could reduce As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic reduction and methylating arsenic mechanism, while the latter might occur with the presence of higher concentrations of arsenic.


Open clinical study of Clopixol-Acuphase (zuclopenthixol acetate) treatment followed by Clopixol Depot in acute psychoses with long-term course tendency.
The evolution of 28 patients displaying acute forms of psychoses (schizophrenia, mania, exacerbation of psychosis in chronic cases) was studied under the treatment with Acuphase Acetate continued with Clopixol Depot. In both therapies a tioxantenic neuroleptic is involved for the acute form of the illness (Acuphase) and for the maintenance treatment (Clopixol Depot). The assessment of the results was carried out on individual observation files using Global Rating Scale (G.R.S.), B.P.R.S. and paraclinical measurement to appreciate the biological tolerance. Favourable effects of treatment were evident in the first 4 days and in six cases even within the first 24 hours. The whole group of patients showed a significant decrease of morbidity evolving from a high severity to a medium and reduced one. The biological tolerance was very good, 6 to 12 months' care.


Patellar fractures--a review of classification, genesis and evaluation of treatment.
The patellar bone is involved in repetitive, load bearing motion sequences every day and functions as a vectorial force translator. A fracture rate of 1% of all skeletal fractures is reported and surgical treatment often required. beside a direct trauma mechanism, indirect mechanism but as well as fatigue fractures after reconstructive knee surgery are published. The fracture management is dependent on the soft tissue condition and a variety of surgical options are known. new generation of low profile plates show promising results but the conventional cerclage wiring technique with K-wires is widely preferred. best functional results with sustainable stability are biomechanically seen after a combined fixation technique using anterior cerclage wiring with cannulated screw fixation. A definite algorithm of treatment of patellar bone fractures is yet not defied but a review of classification and surgical techniques should give assistance in decision making.


Melatonin and nitric oxide: two required antagonists for mitochondrial homeostasis.
The presence of nitric oxide (NO* ) in the mitochondria led to analysis of its source and functions in mitochondrial homeostasis. Studies have revealed the existence of a mtNOS isoform with similar features to nNOS, with some post-traslational modifications, although without the typical signal peptide responsible for addressing proteins to mitochondrion. This isoform may account for the physiological production of NO* related to the respiratory control. During inflammatory conditions there is an excess of NO* in the mitochondria responsible for an increase in reactive oxygen and nitrogen species in sufficient amounts to compromise mitochondrial function. These conditions led to the discovery of the presence of an inducible mtNOS isoform with kinetic properties similar to iNOS. Experiments with knockout mice lacking either nNOS or iNOS further confirmed the existence of these two mtNOS isoforms in mitochondria. Although the increase in NO* in sepsis by inducible mtNOS may have important regulatory functions including the redistribution of oxygen into other pathways under hypoxia, it causes the production of excess NO* that is deleterious for the cell. Melatonin, an endogenous antioxidant, regulates mitochondrial respiration and bioenergetics and protects mitochondria from excess NO* by controlling the activity of mtNOS.