Development and validation of an HPLC-method for the determination of alkaloids in the stem bark extract of Nauclea pobeguinii.
A new method was developed and validated for the quantification of strictosamide in the extract of the stem bark of Nauclea pobeguinii. This plant belongs to the Rubiaceae family and is widely used in the African traditional medicine against malaria and malaria-like symptoms. Alkaloids are suspected to be responsible for the antimalarial activity. One of these alkaloids is strictosamide, already reported to be the major constituent in the root bark of this plant. Because strictosamide was not commercially available another alkaloid, ajmalicine HCl, with comparable properties was used as a secondary standard. The samples of the dried 80% ethanol extract from the stem bark of N. pobeguinii were purified on C(18) solid phase extraction cartridges and analysed using HPLC-UV. The strictosamide used for the validation of the correction factor for response was isolated and purified by means of preparative HPLC and TLC. Although the relative standard deviation (R.S.D.) of 2.6% was still acceptable, the response factor was determined for every analysis based on the ratio of the peak area of strictosamide compared to the peak area of ajmalicine HCl in a concentration of 0.01 mg/ml. The precision of the method according to the time and the concentration, had a R.S.D. value of 2.2% and 2.6%, respectively. The recovery of the method was 92.2% (R.S.D. of 9.4%) which was acceptable. The method has been proven to be suitable for the determination of alkaloids in the extract of the stem bark of N. pobeguinii, according to the ICH guidelines on the validation of analytical methods.


[Ectopic production of amylase by a non-producing type of multiple myeloma].
The patient was a 64-year-old woman who was admitted to our hospital because of lumbago. A diagnosis of multiple myeloma (non-producing type) was made, based on (1) the presence of multiple osteolytic lesions, (2) hypercellular marrow with 64.2% plasmacytoid malignant cells, (3) no monoclonal gamma-globulin was detected in the serum and urine, and (4) abnormal monoclonal gamma-globulin was also not detected in the cytoplasm and membranes of these malignant cells. After several courses of chemotherapy, a pleural effusion infiltrated by myeloma cells developed and the patient's serum contained a markedly increased amylase activity of salivary-type. Amylase activity was also detected in vitro in the supernatant of cultured myeloma cells established from the patient's pleural effusion. The presence of alpha-amylase in the myeloma cells, which were derived from pleural effusion, was demonstrated immuno-histochemically. These observations indicates that amylase was ectopically produced by these myeloma cells. Interestingly, 14 out of 20 metaphases in the cells derived from pleural effusion showed translocation of 1p22 near the region of 1p21, where the amylase gene was assigned.


Recovery after shift work: Relation to coronary risk factors in women.
Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low-density lipoprotein (LDL)-cholesterol were lower after the working period than after the week-off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high-density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week-off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift-working women. It was also shown that susceptible shift workers had worse lipid profiles.


[Pleotropic Effects of Atorvastatin in Patients With Chronic Ischemic Heart Disease].
Examined 52 patients with a diagnosis Ischemic heart disease: stable angina II-III FC CHF I-IIA stage, in combination with hypercholesterolemia aged 53-65 years (58,2+/-6,5), receiving together with traditional antianginal therapy generic atorvastatin Torvakard in the dose of 10 mg/day (20 people) with the level of total cholesterol from 5.0 to 6.50 mmol/l, patients with cholesterol levels from is 6.51 to 8.0 mmol/l was taking Torvakard 20 mg/day (32 person). As a result of 3 months therapy with low doses of Torvakarda decreased level of CRP, endothelin-1, IMT, improving the parameters of endothelium-dependent vasodilation, which shows the positive impact of the drug on morphological and functional parameters of the vascular wall.


A Required Rotation in Clinical Laboratory Management for Pathology Residents: Five-Year Experience at Hofstra Northwell School of Medicine.
Leadership and management training during pathology residency have been identified repeatedly by employers as insufficient. A 1-month rotation in clinical laboratory management (CLM) was created for third-year pathology residents. We report on our experience and assess the value of this rotation. The rotation was one-half observational and one-half active. The observational component involved being a member of department and laboratory service line leadership, both at the departmental and institutional level. Observational participation enabled learning of both the content and principles of leadership and management activities. The active half of the rotation was performance of a project intended to advance the strategic trajectory of the department and laboratory service line. In our program that matriculates 4 residents per year, 20 residents participated from April 2010 through December 2015. Their projects either activated a new priority area or helped propel an existing strategic priority forward. Of the 16 resident graduates who had obtained their first employment or a fellowship position, 9 responded to an assessment survey. The majority of respondents (5/9) felt that the rotation significantly contributed to their ability to compete for a fellowship or their first employment position. The top reported benefits of the rotation included people management; communication with staff, departmental, and institutional leadership; and involvement in department and institutional meetings and task groups. Our 5-year experience demonstrates both the successful principles by which the CLM rotation can be established and the high value of this rotation to residency graduates.


[Segmental arteriographic anomalies in migranous cerebral infarct].
A migranous cerebral infarct (ICM) has the appearance of an ischaemic cerebral lesion which occurs during a migraine crisis and is shown by neuroimaging techniques to be in the corresponding vascular area. Four young patients are described. They fulfilled the clinical and neuroimaging criteria for compatibility with ICM and the protocol for the aetiological study of stroke was normal. Angiography ruled out other causes of ischaemia (dissection, fibromuscular dysplasia, etc.) and showed segmental images of 'vasculitis appearance' similar to these described in Call's syndrome, in 'benign intracranial angiopathy' and in other intracranial vasculopathies or criteria of 'reversible segmental cerebral vasoconstriction'. The pathogenic significance, as with migraine, is still unknown.


Wing 1 of protein HOP2 is as important as helix 3 in DNA binding by MD simulation.
The repair of programmed DNA double-strand breaks through recombination is required for proper association and disjunction of the meiotic homologous chromosomes. Meiosis-specific protein HOP2 plays essential roles in recombination by promoting recombinase activities. The N-terminal domain of HOP2 interacts with DNA through helix 3 (H3) and wing 1 (W1). Mutations in wing 1 (Y65A/K67A/Q68A) slightly weakened the binding but mutations in helices 2 and 3 (Q30A/K44A/K49A) nearly abolished the binding. To better understand such differential effects at atomic level, molecular dynamics simulations were employed. Despite losing some hydrogen bonds, the W1-mutant DNA complex was rescued by stronger hydrophobic interactions. For the wild type and W1-mutant, the protein was found to slide along the DNA grooves as the DNA rolls along its double-helix axis. This motion could be functionally important to facilitate the precise positioning of the single-stranded DNA with the homologous double-stranded DNA. The sliding motion was reduced in the W1-mutant. The H-mutant nearly lost all intermolecular interactions. Moreover, an additional mutation in wing 1 (Y65A/K67A/Q68A/K69A) also caused complete complex dissociation. Therefore, both wing 1 and helix 3 make important contribution to the DNA binding, which could be important to the strand invasion function of HOP2 homodimer and HOP2-MND1 heterodimer. Similar to cocking a medieval crossbow with the archer's foot placed in the stirrup, wing 1 may push the minor groove to cause distortion while helix 3 grabs the major groove.


Terminal differentiation of keratinocytes was damaged in type 2 diabetic mice.
Although skin manifestations are common in diabetic patients, its characteristics are poorly identified. This study explored the differentiation process of keratinocytes in type 2 diabetes mellitus (T2DM) in vivo. Back skin of T2DM model KKAy/TaJcl mice (KKAy) and C57BL/6JJcl mice (control) aged 8 and 12 weeks was used. The mRNA expression of differentiation markers of keratinocytes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of each marker in situ was examined immunohistochemically. KKAy mice showed hyperglycemia versus control mice. The histological findings showed increased thickness and structural impairment of epidermal tissue in KKAy mice. The qRT-PCR revealed that the expression of integrin beta 1 and keratin 14 in KKAy and control mice was identical. However, the expression of involucrin at 8 weeks, keratin 10 at 12 weeks, and filaggrin and loricrin at 8 and 12 weeks was decreased in KKAy mice. Immunohistochemical findings showed that filaggrin was markedly decreased in KKAy mice, though Ki-67 remained unchanged. The terminal differentiation process was impaired in the diabetic skin, while keratinocyte proliferation was preserved. Damaged terminal differentiation of keratinocytes may contribute to impairment of the skin barrier function in diabetic dermatoses.


White matter microstructure predicts cognitive training-induced improvements in attention and executive functioning in schizophrenia.
We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70h (~16weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70h of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.


Use of repaglinide on a pregnant woman during embryogenesis.
In the past few years, oral antihyperglycaemic agents have been considered as an alternative to insulin therapy in the treatment of gestational diabetes. There is still little information available on the safety of these drugs during pregnancy, but there have been several studies published regarding their use. Here we report on the case of a woman who took repaglinide up to the seventh week of pregnancy. Delivery occured with no complications and the newborn showed no malformations. Further studies are required to confirm the safety of repaglinide during pregnancy.


Resonance Raman spectroscopy reveals pH-dependent active site structural changes of lactoperoxidase compound 0 and its ferryl heme O-O bond cleavage products.
The first step in the enzymatic cycle of mammalian peroxidases, including lactoperoxidase (LPO), is binding of hydrogen peroxide to the ferric resting state to form a ferric-hydroperoxo intermediate designated as Compound 0, the residual proton temporarily associating with the distal pocket His109 residue. Upon delivery of this "stored" proton to the hydroperoxo fragment, it rapidly undergoes O-O bond cleavage, thereby thwarting efforts to trap it using rapid mixing methods. Fortunately, as shown herein, both the peroxo and the hydroperoxo (Compound 0) forms of LPO can be trapped by cryoradiolysis, with acquisition of their resonance Raman (rR) spectra now permitting structural characterization of their key Fe-O-O fragments. Studies were conducted under both acidic and alkaline conditions, revealing pH-dependent differences in relative populations of these intermediates. Furthermore, upon annealing, the low pH samples convert to two forms of a ferryl heme O-O bond-cleavage product, whose ν(Fe═O) frequencies reflect substantially different Fe═O bond strengths. In the process of conducting these studies, rR structural characterization of the dioxygen adduct of LPO, commonly called Compound III, has also been completed, demonstrating a substantial difference in the strengths of the Fe-O linkage of the Fe-O-O fragment under acidic and alkaline conditions, an effect most reasonably attributed to a corresponding weakening of the trans-axial histidyl imidazole linkage at lower pH. Collectively, these new results provide important insight into the impact of pH on the disposition of the key Fe-O-O and Fe═O fragments of intermediates that arise in the enzymatic cycles of LPO, other mammalian peroxidases, and related proteins.


Psychiatric Nurses' Views on Caring: Patients and Canine Companions.
Psychiatric nurses are expert care providers for individuals with mental health needs. The art of caring spans across multiple species, is important to understand, and is universal whether intentions are toward individuals or animals. Pets are often cared for and viewed as family members. The current research examined psychiatric nurses' views on the similarities and differences of caring for patients and their pet dogs. Twenty-five nurses were interviewed. Similarities of caring for patients and canines included trusting relationships, companionship, daily basic needs, and improved communication through monitored body language. Differences in caring included personal expectations, unconditional love, and professional boundaries. Understanding the concepts of caring for patients and pet dogs will provide the opportunity for insight into familial versus professional relationships, improve communication with others, and strengthen the human-animal bond. [Journal of Psychosocial Nursing and Mental Health Services, 55(3), 46-52.].


Seoul virus in the Brown Rat ( Rattus norvegicus ) from Ürümqi, Xinjiang, Northwest of China.
Hantavirus infections among human populations are linked to the geographic distribution of the host rodents that carry the viruses. To determine the presence and distribution of hantaviruses in the northern region of Xinjiang Uygur Autonomous Region (XUAR), northwestern China, 844 rodents were captured from five locations in four dissimilar habitats during 2010-14 and examined for Hantavirus infection. Hantavirus nucleic acids were firstly detected in the brown rat ( Rattus norvegicus ) from Ürümqi, China, indicating that the Hantavirus was transmitted into Ürümqi in XUAR and circulated by the brown rat. Our results suggest that the brown rat may act as a natural reservoir for the virus in XUAR.


Rapid Identification of Unknown Organic Iodine in Small-Volume Complex Biological Samples Based on Nanospray Mass Spectrometry Coupled with in-Tube Solid Phase Microextraction.
A new method for rapid screening of unknown organic iodine (OI) in small-volume complex biological samples was developed using in-tube solid phase microextraction (SPME) nanospray mass spectrometry (MS). The method proposed a new identification scheme for OI based on nanospray high-resolution mass spectrometry (HR-MS). The mass ranges of OI ions were confirmed using the t-MS2 scan mode first; then, the possible precursor ions of OI were selected and identified orderly in full MS/ddMS2 and t-MS2 scan modes. Besides, in-tube SPME was used for the pretreatment of small-volume biological samples, and it was the first time in-tube SPME combined with nanospray MS for OI identification. The whole analysis procedure took only 8 min and consumed 50 μL per sample. Using the new method, six kinds of OI added to urine and an unknown OI C12H23O11I in human milk were successfully identified. Moreover, the proposed identification scheme is also suitable for other ambient mass spectrometry (AMS) to determine unknown compounds with characteristic fragment ions.


Shell-mediated phagocytosis to reshape viral-vectored vaccine-induced immunity.
Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.


[Effect of Buzhong Yiqi decoction on PI3K and AKT in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor].
To explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor. Totally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung. Buzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P < 0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P < 0.05), but without statistical difference compared with the blank control group. Among nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.


Cholecystosonography in pregnancy.
Ultrasound is currently the modality of choice for examination of the fetus in pregnancy. Pregnancy is felt to be a possible risk factor for the development of gallstones. The purpose of this study was to determine whether obstetric patients sent for ultrasonic evaluation should have a simultaneous ultrasonic examination of the gallbladder to detect asymptomatic gallstones. In this study, 11.3 per cent of 142 patients were found to have gallstones. The authors conclude that cholecystosonography should be performed on pregnant patients sent for ultrasonic examination.


Protein S-Nitrosylation of Human Cytomegalovirus pp71 Inhibits Its Ability To Limit STING Antiviral Responses.
Human Cytomegalovirus (HCMV) is a ubiquitous pathogen that has coevolved with its host and, in doing so, is highly efficient in undermining antiviral responses that limit successful infections. As a result, HCMV infections are highly problematic in individuals with weakened or underdeveloped immune systems, including transplant recipients and newborns. Understanding how HCMV controls the microenvironment of an infected cell so as to favor productive replication is of critical importance. To this end, we took an unbiased proteomics approach to identify the highly reversible, stress-induced, posttranslational modification (PTM) protein S-nitrosylation on viral proteins to determine the biological impact on viral replication. We identified protein S-nitrosylation of 13 viral proteins during infection of highly permissive fibroblasts. One of these proteins, pp71, is critical for efficient viral replication, as it undermines host antiviral responses, including stimulator of interferon genes (STING) activation. By exploiting site-directed mutagenesis of the specific amino acids we identified in pp71 as protein S-nitrosylated, we found this pp71 PTM diminishes its ability to undermine antiviral responses induced by the STING pathway. Our results suggest a model in which protein S-nitrosylation may function as a host response to viral infection that limits viral spread.IMPORTANCE In order for a pathogen to establish a successful infection, it must undermine the host cell responses inhibitory to the pathogen. As such, herpesviruses encode multiple viral proteins that antagonize each host antiviral response, thereby allowing for efficient viral replication. Human Cytomegalovirus encodes several factors that limit host countermeasures to infection, including pp71. Herein, we identified a previously unreported posttranslational modification of pp71, protein S-nitrosylation. Using site-directed mutagenesis, we mutated the specific sites of this modification thereby blocking this pp71 posttranslational modification. In contexts where pp71 is not protein S-nitrosylated, host antiviral response was inhibited. The net result of this posttranslational modification is to render a viral protein with diminished abilities to block host responses to infection. This novel work supports a model in which protein S-nitrosylation may be an additional mechanism in which a cell inhibits a pathogen during the course of infection.


phenoVein-A Tool for Leaf Vein Segmentation and Analysis.
Precise measurements of leaf vein traits are an important aspect of plant phenotyping for ecological and genetic research. Here, we present a powerful and user-friendly image analysis tool named phenoVein. It is dedicated to automated segmenting and analyzing of leaf veins in images acquired with different imaging modalities (microscope, macrophotography, etc.), including options for comfortable manual correction. Advanced image filtering emphasizes veins from the background and compensates for local brightness inhomogeneities. The most important traits being calculated are total vein length, vein density, piecewise vein lengths and widths, areole area, and skeleton graph statistics, like the number of branching or ending points. For the determination of vein widths, a model-based vein edge estimation approach has been implemented. Validation was performed for the measurement of vein length, vein width, and vein density of Arabidopsis (Arabidopsis thaliana), proving the reliability of phenoVein. We demonstrate the power of phenoVein on a set of previously described vein structure mutants of Arabidopsis (hemivenata, ondulata3, and asymmetric leaves2-101) compared with wild-type accessions Columbia-0 and Landsberg erecta-0. phenoVein is freely available as open-source software.


[Relationship between arterial pressure evolution and free hemoglobin distribution into vascular wall in guinea pigs].
Free hemoglobin (Hb) present at high concentration in plasma--in case of hemolysis, hemoglobin based oxygen carrier (HBOC) administration or in case of subarachnoid hemorrhage--induce hypertension as result of vasoconstriction. In this context, we studied on an exchange transfusion (ET) model at 50% of hematocrit with a HBOC, the distribution of this Hb inside abdominal aortic wall in guinea pigs in relation with mean arterial pressure (MAP) evolution. MAP was monitored during 180 min after ET and rings of abdominal aorta were taken at different times, when modifications of MAP were important, and analyzed by immunohistochemistry and confocal microscopy. Gelofusine 4%, used as control, did not modify MAP while free Hb increased MAP that reached its maximum (53% of hypertension) at t=17 min after the end of ET. MAP started to decrease (45% of hypertension) at t =60 min after ET, and recovered its baseline value at t=180 min. Confocal analysis of the vessel showed that: at 17 min (when hypertension was maximal), free Hb was present in endothelial cells (EC) and in vasa vasorum; at t=60 min (when hypertension decreased) and at t =10 min (when hypertension disappeared), free Hb was detected still in EC, but inside all abdominal aorta wall too. These results suggest in the first time that free Hb could induce a hypertension by direct interaction with EC but would also be unable to maintain this hypertension in spite of its massive tissue distribution.


Diagnostic value of combining CA 19-9 and K-ras gene mutation in pancreatic carcinoma: a meta-analysis.
To assess diagnostic value of Carbohydrate Antigen 19-9 (CA 19-9), combined CA 19-9 and K-ras mutation in plasma DNA in diagnosing patients with pancreatic carcinoma. MEDLINE, EMBASE, the Cochrane Library, Sinomed, CNKI and other databases, from established to November, 2013, were searched for initial studies. All the studies published in English or Chinese relating to the diagnostic value of CA 19-9 and K-ras gene mutation for patients with pancreatic cancer were collected. Methodological quality was assessed. The statistic software called "Meta-disc" (version 1.4) was used for data analysis. 10 studies were included in this meta-analysis. The pooled sensitivity estimate for CA 19-9 (78%) was significantly higher than K-ras mutation (65%). While, for the specificity estimate, K-ras mutation (93%) was significantly higher than CA 19-9 (77%). The pooled DOR estimate for K-ras mutation (21.82) was significantly higher than CA 19-9 (18.36). SROC curves for K-ras mutation showed better diagnostic accuracy than CA 19-9. For CA 19-9 measurement, its diagnostic value decreased in differentiating pancreatic cancer for patients with pancreatitis, especially chronic process. CA 19-9 was a high sensitive and K-ras was a high specific method in diagnosing patients with pancreatic cancer. These two modalities probably act different roles during different conditions in diagnosing pancreatic carcinoma.


Effects of Leptin and Body Weight on Inflammation and Knee Osteoarthritis Phenotypes in Female Rats.
Leptin is a proinflammatory adipokine that contributes to obesity-associated osteoarthritis (OA), especially in women. However, the extent to which leptin causes knee OA separate from the effect of increased body weight is not clear. We hypothesized that leptin is necessary to induce knee OA in obese female rats but not sufficient to induce knee OA in lean rats lacking systemic metabolic inflammation. The effect of obesity without leptin signaling was modeled by comparing female lean Zucker rats to pair fed obese Zucker rats, which possess mutant fa alleles of the leptin receptor gene. The effect of leptin without obesity was modeled in female F344BN F1 hybrid rats by systemically administering recombinant rat leptin versus saline for 23 weeks via osmotic pumps. Primary OA outcomes included cartilage histopathology and subchondral bone micro-computed tomography. Secondary outcomes included targeted cartilage proteomics, serum inflammation, and synovial fluid inflammation following an acute intra-articular challenge with interleukin-1β (IL-1β). Compared to lean Zucker rats, obese Zucker rats developed more severe tibial osteophytes and focal cartilage lesions in the medial tibial plateau, with modest changes in proximal tibial epiphysis trabecular bone structure. In contrast, exogenous leptin treatment, which increased plasma leptin sixfold without altering body weight, caused mild generalized cartilage fibrillation and reduced Safranin O staining compared to vehicle-treated animals. Leptin also significantly increased subchondral and trabecular bone volume and bone mineral density in the proximal tibia. Cartilage metabolic and antioxidant enzyme protein levels were substantially elevated with leptin deficiency and minimally suppressed with leptin treatment. In contrast, leptin treatment induced greater changes in systemic and local inflammatory mediators compared to leptin receptor deficiency, including reduced serum IL-6 and increased synovial fluid IL-1β. In conclusion, rat models that separately elevate leptin or body weight develop distinct OA-associated phenotypes, revealing how obesity increases OA pathology through both leptin-dependent and independent pathways. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Role of MicroRNA-223 and MicroRNA-182 as Novel Biomarkers in Early Detection of Colorectal Cancer.
Colorectal cancer is a common and lethal disease. It is estimated that approximately 145,600 new cases of large bowel cancer are diagnosed annually in the USA. MiRNA-223 and miRNA-182 have been reported in various cancers, such as lung, gastric, breast and colorectal cancer and proposed to be valid and reliable for diagnosis as well as prognosis. This study aimed to determine the role of miR-223 and miR-182 as novel biomarkers for early detection and prognosis of CRC. This case-control study was conducted at the department of Internal Medicine, Aswan University Hospital, in the period from the 1st of February 2020 to the 20th of April 2021. Thirty-five cases and thirty age- and sex-matched controls were included in the study. All patients were subject to complete clinical evaluation, routine investigations, occult blood in stool, serum levels of CEA and CA 19-9, serum levels of miR-223 and miR-182 by quantitative PCR. Significant difference between the two studied groups regarding biomarker changes was found. ROC curve analysis showed that the new markers had excellent diagnostic as well as prognostic criteria. Micro-RNA-223 diagnostic accuracy, sensitivity, specificity, PPV, NPV, FDR and FOR were 97%, 97.1%, 96.7%, 97%, 97%, 3.3% and 2.9%, respectively. Also, micro-RNA-182 diagnostic accuracy, sensitivity, specificity, PPV, NPV, FDR and FOR were 97%, 98%, 96%, 96%, 98%, 3.9% and 2%, respectively. MiR-223 and miR-182 have been discovered to be relevant and reliable biomarkers for the early identification and prognosis of CRC. Increased levels of miR-223 and miR-182 were associated with increased risk of disease progression, and the more accurate the value of miR-223 and miR-182, the earlier the diagnosis of colorectal cancer.


Addition of oleic acid to delipidated bovine serum albumin aggravates renal damage in experimental protein-overload nephrosis.
Non-esterified fatty acids (NEFA) carried on albumin may have a causal role in the development of chronic proteinuria-induced nephropathy. To investigate whether NEFA aggravate renal structural damage, we studied the effects of NEFA addition to delipidated bovine serum albumin (BSA) in protein-overload nephropathy. Three groups of Wistar rats received daily intraperitoneal injections (3 weeks) of either 1 g NEFA-free BSA (BSA-0), or NEFA-free BSA with three (BSA-3) or six (BSA-6) molecules oleic acid added per BSA molecule. An additional group received saline injections only (SAL). Renal damage was evaluated by immunohistochemistry and RT-PCR. Interstitial and glomerular alpha-smooth muscle actin (alpha-SMA, marker of myofibroblast transformation) expression were higher in BSA-3/6 than in saline-injected controls (P < 0.001). Glomerular macrophage influx and desmin (marker of glomerular epithelial cell damage) expression were higher in all BSA-injected rats than SAL (P < 0.001). Interstitial macrophage influx was elevated in BSA-0/3 (P < 0.05) and BSA-6 (P < 0.001) compared to SAL. Addition of six molecules of oleic acid to BSA revealed higher interstitial and glomerular alpha-SMA expression (P < 0.001), increased interstitial macrophage numbers (P < 0.001) and enhanced glomerular desmin expression (P < 0.05) compared to BSA-0. RT-PCR revealed higher glomerular alpha-SMA mRNA expression in BSA-3/6 than SAL (P < 0.001 and 0.05, respectively), interstitial alpha-SMA mRNA was elevated in BSA-6 (P < 0.05). Interstitial TGF-beta1 mRNA expression was significantly higher in BSA-3 than SAL (P < 0.05). These data show that addition of oleic acid to NEFA-free BSA aggravates renal damage, suggesting a role for NEFA in the pathogenesis of proteinuric nephropathies.


Effects of Intra- and Intermolecular Hydrogen Bonding on O-H Bond Photodissociation Pathways of a Catechol Derivative.
The catechol functional motif is thought to play both a structural and photochemical role in the ubiquitous natural pigment, eumelanin. Intramolecular and intermolecular hydrogen bonding interactions lead to a variety of geometries involving the two O-H groups in catechol, but its photophysical behavior in these situations has not been comprehensively characterized. Toward this end, we monitor the UV-induced O-H bond photodissociation reaction in an exemplar catechol derivative, 4- tert-butylcatechol, possessing different intramolecular and intermolecular hydrogen bonding geometries using femtosecond transient absorption spectroscopy measurements in the UV-visible and mid-infrared regions following 265 nm photoexcitation. Three different hydrogen bonding arrangements are obtained by tuning solution complexation equilibria of the catechol with the hydrogen bond acceptor, diethyl ether (Et2O), and are verified computationally. We find that intermolecular hydrogen bonding to the free O-H group in catechol increases its first excited singlet state (S1) lifetime by 2 orders of magnitude (i.e., ∼ 16 to 1410 ps), and that O-H bond dissociation is prevented because Et2O is a poor hydrogen atom acceptor. Complexation of both O-H groups with multiple Et2O molecules further elongates the S1 lifetime to 1670 ps due to shifting of the solution equilibria that describe complex formation. Weakening of the characteristic, intramolecular hydrogen bond of the catechol derivative by intermolecular hydrogen bonding to one or more Et2O molecules does not enhance the rate of O-H bond dissociation.


Incidence and Risk Factors for Leukopenia in Kidney Transplant Recipients Receiving Valganciclovir for Cytomegalovirus Prophylaxis.
Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models. A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia. These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.


Dioxygen oxidation Cu(II) → Cu(III) in the copper complex of cyclo(Lys-dHis-βAla-His): a case study by EXAFS and XANES approach.
A former spectroscopic study of Cu(II) coordination by the 13-membered ring cyclic tetrapeptide c(Lys-dHis-βAla-His) (DK13), revealed the presence, at alkaline pH, of a stable peptide/Cu(III) complex formed in solution by atmospheric dioxygen oxidation. To understand the nature of this coordination compound and to investigate the role of the His residues in the Cu(III) species formation, Cu K-edge XANES, and EXAFS spectra have been collected for DK13 and two other 13-membered cyclo-peptides: the diastereoisomer c(Lys-His-βAla-His) (LK13), and c(Gly-βAla-Gly-Lys) (GK13), devoid of His residues. Comparison of pre-edge peak features with those of Cu model compounds, allowed us to get information on copper oxidation state in two of the three peptides, DK13 and GK13: DK13 contains only Cu(III) ions in the experimental conditions, while GK13 binds only with Cu(II). For LK13/Cu complex, EXAFS spectrum suggested and UV-vis analysis confirmed the presence of a mixture of Cu(II) and Cu(III) coordinated species. Theoretical XANES spectra have been calculated by means of the MXAN code. The good agreement between theoretical and experimental XANES data collected for DK13, suggests that the refined structure, at least in the first coordination shell around Cu, is a good approximation of the DK13/Cu(III) coordination species present at strongly alkaline pH. All the data are consistent with a slightly distorted pyramidal CuN(4) unit, coming from the peptide bonds. Surprisingly, the His side-chains seemed not involved in the final, stable, Cu(III) scaffold.


Acute Renal Failure Associated with Lenalidomide Treatment in Multiple Myeloma: A Rare Occurrence?
Renal failure is a frequent complication of multiple myeloma (MM). Recently, the combination of lenalidomide-dexamethasone has become one of the cornerstone regimens for the treatment of MM. Impairment of renal function exacerbation is a rare, but potential, complication of lenalidomide therapy in plasma cell dyscrasias. We present two patients who developed exacerbation of renal function during their first cycle of therapy with lenalidomide. In the first case, we present a 76-year-old-male with MM and impaired renal function, who declined two weeks after initiation of second-line therapy with lenalidomide. His renal functions improved after discontinuation of lenalidomide and with supportive care. In the second case, we describe a 61-year-old woman who was started on lenalidomide for relapsed MM and admitted to intensive care unit three weeks later due to severe renal failure. Despite intensive supportive care, her renal function deteriorated even more and she died. We conclude that renal failure is an uncommon, but serious, potential complication of lenalidomide therapy in plasma cell dyscrasias, particularly MM. Close monitoring of renal function is clearly recommended during this treatment.


Postnatal demoralisation among women admitted to a hospital mother-baby unit: validation of a psychometric measure.
Demoralisation is a psychological state characterised by experiences of distress and sadness, helplessness, subjective incompetence and hopelessness, in the context of a stressful situation. Experiences of demoralisation may be particularly relevant to women who have recently given birth, who can feel incompetent, isolated and helpless. The psychometric properties of the Demoralisation Scale among women in the postnatal period participating in a clinical program were examined. Women admitted with their infants to a hospital mother-baby unit in Australia for five nights were recruited consecutively (N = 209) and assessed at admission and discharge. The Demoralisation Scale was perceived as relevant and exhibited high reliability, acceptable construct validity and good sensitivity to change. The mean demoralisation score was high (M = 30.9, SD = 15.5) and associated with negative experiences of motherhood and functional impairment, independent of depression and anxiety symptoms. Mean demoralisation decreased significantly after program completion (M = 18.4, SD = 12.4). More participants showed a significant improvement in demoralisation (57.5 %) than in depression (34.8 %) and anxiety (9.8 %) symptoms. Demoralisation can provide a useful framework for understanding and measuring the experiences of women participating in postnatal clinical programs and in directing treatment towards helping women to acquire the necessary caregiving skills and increasing parental efficacy. The Demoralisation Scale is a useful clinical tool for assessing intervention effects.


Does minimally invasive surgery have a different impact on recurrence and overall survival in patients with pancreatic head versus body/tail cancer?
This study sought to investigate the impact of minimally invasive surgery (MIS) on recurrence and overall survival between patients with pancreatic head versus body/tail cancers. The risk factors associated with recurrence and long-term outcomes were analyzed according to tumor location and operative modality. A total of 288 and 87 patients underwent surgical resection for pancreatic head cancer and body/tail cancer, respectively. The perioperative outcomes and histopathologic results were comparable in open and MIS approach in both head and body/tail groups. There was no difference in local or systemic recurrence patterns and disease-free and overall survival rates according to primary tumor location and surgical modality. During subgroup analysis by stage; however, patients with stage III pancreatic head cancer in the MIS group had a decreased disease-free survival compared with those in the open surgery group (p = 0.020). On multivariate analysis, MIS was not a risk factor of total or local recurrences. Recurrence patterns and overall survival rates of patients did not differ according to tumor location and surgical approach. However, patients with stage III pancreatic head cancer in the MIS group showed inferior disease-free survival relative to patients who underwent open surgery.


A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease.
Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA-100 induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4-12%), during aspirin treatment (3-46%) and for day-to-day variability (3-37%) differed markedly between tests and were lowest for VerifyNow. The prevalence of aspirin low-responsiveness also differed between tests (0-9%) and the agreement was low: kappa<or=0.21 for all tests compared with AA-induced LTA (reference test), which correlated best with VerifyNow (r=0.43, p<0.001). Urinary thromboxane metabolites did not correlate with any platelet function test, whereas serum thromboxane correlated with VerifyNow Aspirin (r=0.41, p=0.001). Overall, repeatability was moderate and the correlation between tests was low. VerifyNow Aspirin proved most reproducible, and this was the only assay showing a significant positive correlation with serum thromboxane. This study demonstrated that conclusions based on platelet function testing strongly depend on the assay used.


Longitudinal effects of systemic inflammation markers on periodontitis.
Systemic low-grade inflammation represents a central hallmark of chronic diseases and has been proposed as the underlying mechanism linking factors like obesity or diabetes with periodontitis. However, the impact of inflammatory markers on periodontitis has not yet been investigated. The study population comprised 1784 subjects from the Study of Health in Pomerania with complete 11-year follow-up. Fibrinogen and white blood cell (WBC) counts were measured as markers of inflammation. Periodontitis was assessed by probing depth (PD), clinical attachment loss (CAL) and the CDC/AAP case definition. Multilevel regression analyses revealed significant coefficients for the impact of both inflammation markers on the percentage of sites with PD/CAL ≥ 3 mm. Increases in fibrinogen about 1 g/l were associated with 3.0% and 2.7% more sites with PD/CAL ≥ 3 mm respectively. Consistent associations were found using mean values of PD/CAL but not using missing teeth or caries. Regarding the CDC/AAP case definition, 11-year changes in fibrinogen and WBC counts were significantly associated with ≥1 category progression (OR: 1.36 and 1.11). Fibrinogen levels and WBC counts showed consistent long-term associations with PD, CAL and the CDC/AAP case definition. Results indicate that systemic low-grade inflammation might indeed represent one possible pathway for effects of obesity, diabetes or other chronic inflammatory conditions on periodontitis.


[Acute antihypertensive effect of captopril in hypertensive patients: with special reference to kallikrein-kinin system].
In order to clarify the role of the kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibition, captopril was administered in a single oral dose of 50 mg to 17 hypertensive patients, of whom 14 had essential hypertension, one had chronic renal failure, one had primary aldosteronism, and one had glucocorticoid responsive hyperaldosteronism. Captopril lowered blood pressure remarkably in either low-renin or normal-, and high-renin hypertensives, however, there was no significant relationship between the fall in blood pressure and pretreatment levels of plasma renin activity (PRA) in any of the patients any time after the administration. PRA was significantly increased in normal- and high-renin hypertensives but not in low-renin patients. Plasma aldosterone concentration (PAC) was decreased significantly in normal- and high-renin patients, while no significant change in PAC was observed in patients with low-renin activity. Captopril elevated plasma bradykinin concentration (PBK) from a control value of 12.5 +/- 4.1 (mean +/- s.d.) to 20.3 +/- 7.7 pg/ml (p less than 0.001) at 30 min, and there was a significant correlation between changes in PBK and changes in mean blood pressure 120 min after the administration in all the patients (r = 0.741, p less than 0.01, n = 17). In one patient with primary aldosteronism, PBK increased from a baseline of 10.0 to a maximum value of 19.0 pg/ml, corresponding to the rapid fall in blood pressure. Also, in one patient with glucocorticoid responsive hyperaldosteronism, captopril increased PBK from a control of 14.1 to 27.9 pg/ml at 30 min, corresponding to the marked fall in blood pressure from 170/106 to 136/90 mmHg. From these findings, it is suggested that the accumulation of kinins following captopril administration plays a major role in the short-term reduction of blood pressure in hypertensive patients, especially in those with low renin-angiotensin activity.


Subcellular distribution of a fluorescence-labeled combi-molecule designed to block epidermal growth factor receptor tyrosine kinase and damage DNA with a green fluorescent species.
To monitor the subcellular distribution of mixed epidermal growth factor (EGF) receptor (EGFR)-DNA targeting drugs termed combi-molecules, we designed AL237, a fluorescent prototype, to degrade into a green fluorescent DNA damaging species and FD105, a blue fluorescent EGFR inhibitor. Here we showed that AL237 damaged DNA in the 12.5 to 50 mumol/L range. Despite its size, it blocked EGFR phosphorylation in an enzyme assay (IC(50) = 0.27 mumol/L) and in MDA-MB468 breast cancer cells in the same concentration range as for DNA damage. This translated into inhibition of extracellular signal-regulated kinase 1/2 or BAD phosphorylation and downregulation of DNA repair proteins (XRCC1, ERCC1). Having shown that AL237 was a balanced EGFR-DNA targeting molecule, it was used as an imaging probe to show that (a) green and blue colors were primarily colocalized in the perinuclear and partially in the nucleus in EGFR- or ErbB2-expressing cells, (b) the blue fluorescence associated with FD105, but not the green, was colocalized with anti-EGFR red-labeled antibody, (c) the green fluorescence of nuclei was significantly more intense in NIH 3T3 cells expressing EGFR or ErbB2 than in their wild-type counterparts (P < 0.05). Similarly, the growth inhibitory potency of AL237 was selectively stronger in the transfectants. In summary, the results suggest that AL237 diffuses into the cells and localizes abundantly in the perinuclear region and partially in the nucleus where it degrades into EGFR and DNA targeting species. This bystander-like effect translates into high levels of DNA damage in the nucleus. Sufficient quinazoline levels are released in the cells to block EGF-induced activation of downstream signaling. Mol Cancer Ther; 9(4); 869-82. (c)2010 AACR.


[Physiopathology, diagnosis and treatment of breast cancer].
The organised screening of breast cancer, the identification of the type of lesion and the staging determine the treatment plan for this disease. The most common cancer to affect women in France and in Europe, it represents 1/3 of cancers in women and 1/4 of all cancers.


[Schwannoma of the parapharyngeal space].
Schwannoma is a benign neoplasm that develops from the Schwann cells of the nerve sheath. The share of neurogenic tumors of the parapharyngeal space accounts for 0.5% of all neoplasms of this localization. The article demonstrates a case from practice, presents the clinical features, diagnostics and methods of treatment for patients with pharyngeal neuromas. The peculiarity of the presented clinical observation is due to the rare occurrence of this pathology and the large size of the schwannoma in the long-term asymptomatic course of the disease.


Seed-caching responses to substrate and rock cover by two Peromyscus species: implications for pinyon pine establishment.
We examined whether pinyon mice ( Peromyscus truei) and brush mice ( P. boylii) could act as directed dispersal agents of pinyon pine ( Pinus edulis) through differential responses to soil particle size and rock cover. In field experiments, we allowed mice to either cache pinyon seeds or recover artificially cached seeds (pilfer) from quadrats containing large- or small-particle soils. Both species placed most (70%) seed caches in small-particle soil. Pilfering was the same from both particle sizes in the first year, while more seeds were pilfered from large-particle soils in the second year. In separate experiments, rock cover interacted with soil particle size, with both species placing over 50% of their caches in small-particle soil with rock cover. Overall, we found greater seed-caching in small-particle soils near rocks, with equal or lower pilfering from small-particle soils, suggesting more seeds would survive in small-particle soils near rock cover. Three lines of evidence supported the hypothesis that mice could act as directed dispersers by moving pinyon seeds to beneficial microsites for germination and establishment. First, in greenhouse experiments, pinyon seed germination was 4 times greater in small-particle soil cores than in large-particle soil cores. Second, soils near rocks had significantly higher water content than areas of open soil at the driest time of the year, a critical factor for seedling survival in the arid southwestern USA. Third, 75% of juvenile pinyon trees were growing in small-particle soils, and 45% were growing near rock nurses.


Family cluster of three recovered cases of pneumonia due to severe acute respiratory syndrome coronavirus 2 infection.
The coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in late 2019 and has affected more than 1 270 000 people worldwide. The numbers of reported cases continue to rise and threaten global health. Transmissions among family members are frequently observed, although the route of transmission is partially known. Here we report three cases of SARS-CoV-2 infection within one family. Sequencing of the S gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. Following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. Our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/moderate pneumonia in COVID-19 cases.


Comparison of δ81Br and δ37Cl composition of volatiles, salt precipitates, and associated water in terrestrial evaporative saline lake systems.
This study provides the first characterization of the variability of bromine and chlorine stable isotopic composition in evaporites, associated residual brines, and shoreline gases in terrestrial evaporative saline lakes. The lakes investigated here are groundwater discharge locations, and include both potash-rich alkaline lakes and sodic-dominated neutral pH lakes at a variety of salinities and evaporative stages. The chlorine and bromine isotope systems behave consistently different during evaporative salt precipitation, with 37Cl more enriched in the salt than in the fluid, but 81Br more enriched in the fluid compared with the precipitated salt. The 81Br concentration of shore off-gassing was even smaller than mineral precipitate compositions. The trends observed for bromine isotopes are surprising compared with published laboratory studies, indicating that a process besides inorganic mineral precipitation is affecting δ81Br. Additional processes explored include diffusion, salt deflation, microbial and photolytic conversion to the gas phase, and oxidative bromination of organic matter. Dedicated to Professor Peter Fritz on the occasion of his 80th birthday.


Preventing youth use of tobacco products: the role of nursing.
In the 1997 Youth Risk Behavior Survey (Centers for Disease Control and Prevention [CDC], 1998a), 70.2% of high school students reported cigarette use, 36.4% were current cigarette smokers, and 16.7% reported frequent cigarette use (as measured by more than 20 in the last 30 days). Current tobacco use by all racial and ethnic groups is 42.7% (48.2% male, 36.0% female). Preventing youth tobacco use requires nurses to be active in many different domains. Public health experts agree that tobacco control efforts must target youth, with the goal of preventing tobacco product use and dependence. Nurses need to be actively involved in directing resources and talents toward public awareness and tobacco prevention programs, formulating public policy initiatives to control youth access to tobacco, and initiating cessation programs for youth. Efforts can be targeted at the schools, community, and health care system, as well as the public policy arena and media campaigns.


Drug-induced peripheral neuropathy in a patient with psoriatic arthritis.
A patient with psoriatic arthritis developed a peripheral neuropathy while taking hydroxychloroquine and naproxen. Although it was initially suspected that hydroxychloroquine was responsible for the neuropathy, subsequent rechallenge with naproxen demonstrated that clinical and electrophysiologic findings were related to routine pharmacologic doses of naproxen.


A linear mixed-effects statistical model for in-vivo evaluation of recombinant human growth hormone implants in hypophysectomized rats.
We have used a linear mixed-effects statistical model to evaluate previously published results of body weight evolution in hypophysectomized (Hpx) rats after administration of two different controlled-release formulations of recombinant human growth hormone (rhGH). Using the linear mixed-effects model, it was possible to distinguish between maximal pharmacological response with time in different subjects and relate it to the structure of the different formulations, the release of the hormone from them and the time necessary to obtain a quantitative result as a consequence of the hormone activity, contrary to the multivariate variance analysis model (MANOVA) used in our earlier work. These results confirmed that the maximum body weight gain obtained with the controlled-release implants is similar to that with subcutaneous rhGH, but with the advantage that laminar biodegradable implants need to be administered only once every 2 weeks.


[Nurse's opinion on the applicability of the nursing process at the intensive care unit].
This paper aimed to identify the nurses opinion about the nursing process in the Intensive Care Unit (ICU), and the knowledge they had about this such assistance methodology. The method of investigation used had an qualitative approach, of the descriptive and exploratory kind, applying semi structured interviews to five nurses of ICU at a General Hospital of the south area of Rio Grande do Sul. It was verified that: the nurses interviewed had little knowledge about the subject, some referred using daily evolution and nursing prescription. Mostly, all recognize the importance of this assistance methodology, but consider essential that all the nursing staff should be trained and prepared to elaborate and execute it.


[Lipopolysaccharide-specific antibodies in intestinal lavage fluid, bile and serum of mice after oral application of inactivated Escherichia coli].
The formation of antibodies against lipopolysaccharide in the mouse after daily administration of 10(10) killed Escherichia coli M17 (serotype 02:K1) was studied. An IgA response in gut is already established at the first day after an immunization period of 5 days. The kinetics of antibody formation in gut lavage fluid and bile are similar. In comparison lipopolysaccharide-specific IgG antibodies against lipopolysaccharide in serum are raised later.


Treatise on Analytic Nonlinear Optimal Guidance and Control Amplification of Strictly Analytic (Non-Numerical) Methods.
Optimal control is seen by researchers from a different perspective than that from which the industry practitioners see it. Either type of user can easily become confounded when deciding which manner of optimal control should be used for guidance and control of mechanics. Such optimization methods are useful for autonomous navigation, guidance, and control, but their performance is hampered by noisy multi-sensor technologies and poorly modeled system equations, and real-time on-board utilization is generally computationally burdensome. Some methods proposed here use noisy sensor data to learn the optimal guidance and control solutions in real-time (online), where non-iterative instantiations are preferred to reduce computational burdens. This study aimed to highlight the efficacy and limitations of several common methods for optimizing guidance and control while proposing a few more, where all methods are applied to the full, nonlinear, coupled equations of motion including cross-products of motion from the transport theorem. While the reviewed literature introduces quantitative studies that include parametric uncertainty in nonlinear terms, this article proposes accommodating such uncertainty with time-varying solutions to Hamiltonian systems of equations solved in real-time. Five disparate types of optimum guidance and control algorithms are presented and compared to a classical benchmark. Comparative analysis is based on tracking errors (both states and rates), fuel usage, and computational burden. Real-time optimization with singular switching plus nonlinear transport theorem decoupling is newly introduced and proves superior by matching open-loop solutions to the constrained optimization problem (in terms of state and rate errors and fuel usage), while robustness is validated in the utilization of mixed, noisy state and rate sensors and uniformly varying mass and mass moments of inertia. Compared to benchmark, state-of-the-art methods state tracking errors are reduced one-hundred ten percent. Rate tracking errors are reduced one-hundred thirteen percent. Control utilization (fuel) is reduced eighty-four percent, while computational burden is reduced ten percent, simultaneously, where the proposed methods have no control gains and no linearization.


Infrared radiometry experiment on mariner 9.
The brightness temperatures at 10 and 20 micrometers measured by the Mariner 9 infrared radiometer differ substantially from those predicted by the radiometer results of Mariners 6 and 7. The results indicate a significant latitude-dependent contribution of the atmospheric dust to the observed thermal emission.


Total Synthesis of Leupyrrin B1: A Potent Inhibitor of Human Leukocyte Elastase.
The total synthesis of leupyrrin B1 was accomplished by an expedient strategy that involves an optimized HATU-mediated amide coupling protocol of elaborate substrates. The generally useful procedure was also successfully applied in an improved total synthesis of leupyrrin A1. Finally, leupyrrins A1 and B1 were evaluated toward a panel of proteases, and human leukocyte elastase was discovered as a molecular target of the leupyrrins.


An audit of the assessment and management of patients admitted to Christchurch Hospital with chronic obstructive pulmonary disease.
To audit the assessment and management of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) during three months of the winter of 1992. Consensus management guidelines were developed as the basis for the audit. Consecutive cases were audited by review of the case notes. Half were admitted initially under a respiratory physician and half under a general physician. Ninety-five cases were audited. The overall standard of medical assessment was adequate but a number of deficiencies were identified. The mean duration of stay in hospital was nine days. In the emergency department the use of pulse oximetry in preference to arterial blood gas analysis led to failure to diagnose significant ventilatory failure in five cases. Initial assessment by junior medical staff failed to include comment about level of consciousness in 50% of cases and chest hyperinflation in 40%. Oxygen therapy was given in 87% of cases, but was not prescribed in one third and was often not adequately monitored. Peak flow monitoring was performed on admission in 74% of cases and arterial blood gas measurement in 81%. Over 90% of patients were given nebulised bronchodilator therapy with both nebulised ipratropium bromide and salbutamol. Antibiotics were given in 77% of cases. Corticosteroids were given in 95% of cases, usually orally. Sedatives were prescribed inappropriately in six cases where there was acute ventilatory failure. Four patients died in hospital, none unexpectedly. Three patients were mechanically ventilated and all survived to leave hospital. There was no discharge summary in the case records in 29% of cases. Standards of assessment and treatment were adequate. Several areas were identified where improvements are required, particularly in the prescribing and monitoring of oxygen therapy. Hospital-wide guidelines for the management of COPD are to be developed.


Parental age and childhood cancer risk: A Danish population-based registry study.
Though the association between parental age at child's birth and the risk of childhood cancer has been previously investigated, the evidence to date is inconclusive and scarce for rarer cancer types. Cancer cases (N=5,856) were selected from all children born from 1968 to 2014 and diagnosed from 1968 to 2015 in Denmark at less than 16 years of age listed in the nationwide Danish Cancer Registry. Cases were individually matched to controls (1:100) on sex and year of birth with a total of 585,594 controls randomly sampled from all live births in Denmark from the Danish Central Population Registry. Parental age at child's birth was extracted from the Central Population Registry. Conditional logistic regression models were used to estimate odds ratios for the association between parental age at child's birth and childhood cancer risk. Parental age was modeled as both categorical (referent group, parents aged 25-29) and continuous per 5-year increase in age. Offspring of older mothers were at an increased risk of acute lymphoblastic leukemia [OR=1.10, 95% CI: (1.02, 1.19) per 5-year increase in age]. Older maternal age (40+) increased the risk of non-Hodgkin lymphoma [OR=1.96, 95%CI: (1.12, 3.43)]. The risk of Wilms' tumor also appeared elevated with older paternal age [OR=1.11, 95% CI: (0.97, 1.28) per 5-year increment in age]. Older parental age was a risk factor for various childhood cancers in Danish children. Further investigation of the biological and social factors that may be contributing to these associations is warranted.


Mental rotational ability is correlated with spatial but not verbal working memory performance and P300 amplitude in males.
This study investigated how both sex and individual differences in a mental rotation test (MRT) influence performance on working memory (WM). To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory.


Effects of Using Different Indirect Techniques on the Calculation of Reference Intervals: Observational Study.
Reference intervals (RIs) play an important role in clinical decision-making. However, due to the time, labor, and financial costs involved in establishing RIs using direct means, the use of indirect methods, based on big data previously obtained from clinical laboratories, is getting increasing attention. Different indirect techniques combined with different data transformation methods and outlier removal might cause differences in the calculation of RIs. However, there are few systematic evaluations of this. This study used data derived from direct methods as reference standards and evaluated the accuracy of combinations of different data transformation, outlier removal, and indirect techniques in establishing complete blood count (CBC) RIs for large-scale data. The CBC data of populations aged ≥18 years undergoing physical examination from January 2010 to December 2011 were retrieved from the First Affiliated Hospital of China Medical University in northern China. After exclusion of repeated individuals, we performed parametric, nonparametric, Hoffmann, Bhattacharya, and truncation points and Kolmogorov-Smirnov distance (kosmic) indirect methods, combined with log or BoxCox transformation, and Reed-Dixon, Tukey, and iterative mean (3SD) outlier removal methods in order to derive the RIs of 8 CBC parameters and compared the results with those directly and previously established. Furthermore, bias ratios (BRs) were calculated to assess which combination of indirect technique, data transformation pattern, and outlier removal method is preferrable. Raw data showed that the degrees of skewness of the white blood cell (WBC) count, platelet (PLT) count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) were much more obvious than those of other CBC parameters. After log or BoxCox transformation combined with Tukey or iterative mean (3SD) processing, the distribution types of these data were close to Gaussian distribution. Tukey-based outlier removal yielded the maximum number of outliers. The lower-limit bias of WBC (male), PLT (male), hemoglobin (HGB; male), MCH (male/female), and MCV (female) was greater than that of the corresponding upper limit for more than half of 30 indirect methods. Computational indirect choices of CBC parameters for males and females were inconsistent. The RIs of MCHC established by the direct method for females were narrow. For this, the kosmic method was markedly superior, which contrasted with the RI calculation of CBC parameters with high |BR| qualification rates for males. Among the top 10 methodologies for the WBC count, PLT count, HGB, MCV, and MCHC with a high-BR qualification rate among males, the Bhattacharya, Hoffmann, and parametric methods were superior to the other 2 indirect methods. Compared to results derived by the direct method, outlier removal methods and indirect techniques markedly influence the final RIs, whereas data transformation has negligible effects, except for obviously skewed data. Specifically, the outlier removal efficiency of Tukey and iterative mean (3SD) methods is almost equivalent. Furthermore, the choice of indirect techniques depends more on the characteristics of the studied analyte itself. This study provides scientific evidence for clinical laboratories to use their previous data sets to establish RIs.


Infection recurrence following minimally invasive treatment in patients with infectious pancreatic necrosis.
In recent decades, an increasing number of patients have received minimally invasive intervention for infected pancreatic necrosis (IPN) because of the benefits in reducing postoperative multiple organ failure and mortality. However, there are limited published data regarding infection recurrence after treatment of this patient population. To investigate the incidence and prediction of infection recurrence following successful minimally invasive treatment in IPN patients. Medical records for 193 IPN patients, who underwent minimally invasive treatment between February 2014 and October 2018, were retrospectively reviewed. Patients, who survived after the treatment, were divided into two groups: one group with infection after drainage catheter removal and another group without infection. The morphological and clinical data were compared between the two groups. Significantly different variables were introduced into the correlation and multivariate logistic analysis to identify independent predictors for infection recurrence. Sensitivity and specificity for diagnostic performance were determined. Of the 193 IPN patients, 178 were recruited into the study. Of them, 9 (5.06%) patients died and 169 patients survived but infection recurred in 13 of 178 patients (7.30%) at 7 (4-10) d after drainage catheters were removed. White blood cell (WBC) count, serum C-reactive protein (CRP), interleukin-6, and procalcitonin levels measured at the time of catheter removal were significantly higher in patients with infection than in those without (all P < 0.05). In addition, drainage duration and length of the catheter measured by computerized tomography scan were significantly longer in patients with infection (P = 0.025 and P < 0.0001, respectively). Although these parameters all correlated positively with the incidence of infection (all P < 0.05), only WBC, CRP, procalcitonin levels, and catheter length were identified as independent predictors for infection recurrence. The sensitivity and specificity for infection prediction were high in WBC count (≥ 9.95 × 109/L) and serum procalcitonin level (≥ 0.05 ng/mL) but moderate in serum CRP level (cut-off point ≥ 7.37 mg/L). The catheter length (cut-off value ≥ 8.05 cm) had a high sensitivity but low specificity to predict the infection recurrence. WBC count, serum procalcitonin, and CRP levels may be valuable for predicting infection recurrence following minimally invasive intervention in IPN patients. These biomarkers should be considered before removing the drainage catheters.


Growth of semiconducting GaN hollow spheres and nanotubes with very thin shells via a controllable liquid gallium-gas interface chemical reaction.
An in situ liquid gallium-gas interface chemical reaction route has been developed to synthesize semiconducting hollow GaN nanospheres with very small shell size by carefully controlling the synthesis temperature and the ammonia reaction gas partial pressure. In this process the gallium droplet does not act as a catalyst but rather as a reactant and a template for the formation of hollow GaN structures. The diameter of the synthesized hollow GaN spheres is typically 20-25 nm and the shell thickness is 3.5-4.5 nm. The GaN nanotubes obtained at higher synthesis temperatures have a length of several hundreds of nanometers and a wall thickness of 3.5-5.0 nm. Both the hollow GaN spheres and nanotubes are polycrystalline and are composed of very fine GaN nanocrystalline particles with a diameter of 3.0-3.5 nm. The room-temperature photoluminescence (PL) spectra for the synthesized hollow GaN spheres and nanotubes, which have a narrow size distribution, display a sharp, blue-shifted band-edge emission peak at 3.52 eV (352 nm) due to quantum size effects.


Epidemiology of Helicobacter pylori infection in dyspeptic Ghanaian patients.
Helicobacter pylori is a gram-negative urease-producing bacterium causally linked with gastritis, peptic ulcer disease and gastric adenocarcinoma. Infection is more frequent and acquired at an earlier age in developing countries compared to European populations. The incidence of Helicobacter pylori infection in dyspeptic Ghanaian patients was 75.4%. However, epidemiological factors associated with infection vary across populations. This study used a cross-sectional design to consecutively sample dyspeptic patients at the Endoscopy Unit of the Korle-Bu Teaching Hospital, Accra between 2010 and 2012. The study questionnaire elicited their epidemiological clinical characteristics. Helicobacter pylori infection was confirmed by rapid-urease examination of antral biopsies at upper Gastro-intestinal endoscopy. The sample population of dyspeptic patients attending the Endoscopy Unit for upper GI endoscopy yielded 242 patients of which 47.5% were females. The age distribution of H. pylori-infection was even across most age - groups, ranging from 69.2% (61 - 70) years to 80% (21 - 30) years. Helicobacter pylori prevalence decreased across areas mapping to the three residential classes in accordance with increasing affluence with rural areas having the highest prevalence. The unemployed and patients in farming had relatively high Helicobacter pylori infection rates of 92.3% and 91.7% respectively. Helicobacter pylori is endemic in Ghana but the persistently high prevalence across age groups despite significant community anti-microbial use suggests likely recrudescence or re-infection from multiple sources in a developing country. Socio-cultural factors such as residential class and farming may be facilitating factors for its continued prevalence.


Clinical immunotoxicity of therapeutic proteins.
Therapeutic proteins are proteins engineered in the laboratory for pharmaceutical use. Although they tend to offer a better safety margin than most synthetic small molecules because they are processed by the same pathways as natural proteins in the human body, or mimic or replace natural proteins that are missing or defective, they can induce a variety of adverse effects in human patients among which immunotoxic effects deserve particular attention. Infectious complications and virus-induced neoplasias are the main consequences of intended or unexpected immunosuppression. They have been primarily described with anti-TNF-alpha drugs and anticancer monoclonal antibodies (mAbs) whose immunosuppressive effects can be largely anticipated from their mechanism of action. Cytokine release-associated adverse reactions ranging from mild-to-moderate flu-like reactions to severe cytokine release syndromes, or exceptionally cytokine storm, are now an issue of chief concern. They have been observed with most of the therapeutic proteins in current use. Acute infusion reactions whose clinical features are somewhat similar have been variably described with many mAbs. Immunostimulatory properties are suspected to account for the occurrence of more frequent autoimmune diseases as seen in patients treated with recombinant cytokines such as the IFNs-alpha and rIL-2. The risk of more frequent hypersensitivity reactions to unrelated allergens is also suspected to be a potential consequence of immunostimulation but compelling evidence is limited to radiocontrast media-induced hypersensitivity reactions in IL-2 treated cancer patients. In addition, recombinant cytokines can inhibit cytochrome P450 dependent biotransformation pathways with resulting alterations in the pharmacokinetics of the combined drugs at therapeutic dose. Because of their structure and origin, therapeutic proteins are intrinsically immunogenic. Despite extensive laboratory and clinical studies that were instrumental in delineating general concepts about key factors involved in immunogenicity, it is impossible nowadays to anticipate to what extent a novel therapeutic protein will be immunogenic in human patients. Specific antibodies are frequently detected in the sera of treated patients. They are often inconsequential but can also be neutralizing and result in decreased efficacy. Anaphylactic reactions induced by human therapeutic proteins have been rarely reported and true serum sickness extremely rarely. Because the immunotoxic effects of therapeutic proteins are frequent, sometimes severe and even potentially life-threatening, there is an urgent need to improve our capacity to anticipate the immunotoxic risks of novel therapeutic proteins and this could be achieved by the development of clinical immunotoxicology.


Galanin of the homologous species inhibits insulin secretion in the rat and in the pig.
It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species-specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg-1) abolished the glucose- (0.56 mmol kg-1) induced increase in plasma insulin levels. In vitro, rat galanin (10(-9) to 10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min-1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.


LRRK2 gene in Parkinson disease: mutation analysis and case control association study.
In addition to the four well-confirmed genes linked to early-onset Parkinson disease (PD) (SNCA, PARKIN, DJ-1, and PINK1), mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have recently been identified in families with autosomal dominant late-onset PD. To perform mutation analysis of LRRK2 in probands of families showing dominant inheritance of PD and to conduct a case control association study to test the hypothesis that common coding variations might be associated with increased susceptibility to PD. All 51 LRRK2 coding exons were sequenced in 23 probands and the mutation frequencies were evaluated in 180 neurologically normal control subjects. For the association study the authors genotyped four coding LRRK2 polymorphisms in 250 normal control subjects and 121 patients with PD (predominantly white patients of Canadian origin), 84% of whom had age at onset before 50 years and 42% had a positive family history. The authors identified three probands with heterozygous LRRK2 mutations: two of them have the known G2019S substitution and one proband has a novel I1371V substitution. Mutation analysis of a large family demonstrated complete segregation of the G2019S with PD. However, there was no association between PD and any of the four polymorphisms at the allelic or genotypic levels (p > 0.17). Furthermore, the authors did not detect a modifying effect for any genotype or of APOE genotypes upon the age at onset in the PD group (p > 0.20). The results support the prior suggestion that LRRK2 mutations cause PD. The disease in the families reported here presents a phenotype indistinguishable from typical PD. All three families demonstrate a very variable age at onset that is not explained by APOE genotypes. The common coding variations in the LRRK2 gene neither constitute strong PD risk factors nor modify the age at onset; however, the possibility of a modest risk effect remains to be assessed in large datasets.


Small solid renal masses: characterization by diffusion-weighted MRI at 3 T.
To describe the appearance of small solid renal lesions (≤3 cm) on diffusion-weighted magnetic resonance imaging (MRI) and to determine whether ADC measurements may help to differentiate benign from malignant small solid renal masses. Thirty-five patients with 47 small renal masses (23 malignant, 24 benign) who underwent 3 T MRI of the kidney using diffusion-weighted sequences (b values of 0 and 1000 s/mm(2)) were retrospectively evaluated. Qualitative and quantitative analysis of diffusion-weighted images was performed. Most lesions were hyperintense to kidney on high b-value diffusion-weighted images and hypointense on apparent diffusion coefficient (ADC) map. The mean ADC of the lesions was significantly lower than that of kidney (1.22 ± 0.3 versus 1.85 ± 0.12 mm(2)/s; p < 0.005). The mean ADC was significantly different between renal cell carcinomas (1.2 ± 0.01 mm(2)/s), metastases (1.25 ± 0.04 mm(2)/s), angiomyolipoma (1.07 ± 0.3 mm(2)/s) and oncocytomas (1.56 ± 0.08 mm(2)/s; p < 0.05). The mean ADC of clear cell renal cell carcinomas was significantly different from that of non-clear cell renal cell carcinomas (1.38 ± 0.34 versus 0.83 ± 0.34 mm(2)/s; p < 0.005). No significant difference was found between mean ADC of fat containing and minimal fat angiomyolipomas (1.06 ± 0.48 versus 1.11 ± 0.33 mm(2)/s). Small solid renal masses are hyperintense on high b value and have different ADC values.


Area-Law Entangled Eigenstates from Nullspaces of Local Hamiltonians.
Eigenstate thermalization in quantum many-body systems implies that eigenstates at high energy are similar to random vectors. Identifying systems where at least some eigenstates are nonthermal is an outstanding question. In this Letter we show that interacting quantum models that have a nullspace-a degenerate subspace of eigenstates at zero energy (zero modes), which corresponds to infinite temperature, provide a route to nonthermal eigenstates. We analytically show the existence of a zero mode which can be represented as a matrix product state for a certain class of local Hamiltonians. In the more general case we use a subspace disentangling algorithm to generate an orthogonal basis of zero modes characterized by increasing entanglement entropy. We show evidence for an area-law entanglement scaling of the least-entangled zero mode in the broad parameter regime, leading to a conjecture that all local Hamiltonians with the nullspace feature zero modes with area-law entanglement scaling and, as such, break the strong thermalization hypothesis. Finally, we find zero modes in constrained models and propose a setup for observing their experimental signatures.


Current concepts in lip reconstruction.
Approximately 25% of all oral cavity carcinomas involve the lips, and the primary management of these lesions is complete surgical resection. The management of the resulting lip defect remains a significant reconstructive challenge, requiring meticulous preoperative planning and surgical technique to optimize the functional and cosmetic outcome. Reviewed here are the accepted techniques of lip reconstruction, as well newer techniques that have been reported. There have been no major advances in lip reconstruction; rather, continued improvement on accepted techniques. The main goals of reconstruction remain the restoration of oral competence, maintenance of oral opening, and the restoration of normal anatomic relations such that both the active (smile) and passive (form) cosmetic outcome is acceptable. The reconstruction should be tailored to the individual needs of the patient and should take into account the patient's condition, local tissue characteristics, previous treatment(s), and functional needs (eg, denture use), in addition to the size and location of the defect. The lips play a key role in facial expression, speech, and eating. This requires meticulous attention to preoperative planning and surgical technique to maximize the functional and cosmetic outcome. It is important to assess local tissue characteristics (skin laxity) and previous treatment (surgery and/or irradiation) before the surgical plan is made final. Local tissue should be used whenever possible to provide the least donor site morbidity and the best overall tissue color and texture match. Whenever possible, dynamic reconstruction should be attempted. Careful preoperative assessment and planning will allow the surgeon to reach an acceptable balance between form and function with the reconstruction.


Development of a reverse transcription (RT) polymerase chain reaction (PCR) method for the detection of human norovirus in bivalve molluscs.
Noroviruses are significant seafood-borne pathogens, commonly associated with the consumption of filter feeding bivalve molluscs. Here, we report the development of a reverse transcription polymerase chain reaction (RT-PCR) method using primers based on the RNA-dependent RNA polymerase gene of norovirus genogroup II (NoV GII). Samples of bivalves were processed for the concentration of virus and extraction of RNA, followed by reverse transcription PCR. A total of 50 molluscan shellfish samples were analyzed, of which 16 samples yielded positive amplifications of norovirus nucleic acid. The PCR method described here, involving a single set of primers, is useful for rapid screening of shellfish for NoV GII.


Mixed dyslipidemia among patients using lipid-lowering therapy in French general practice: an observational study.
Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) are associated with an increased incidence of coronary heart disease (CHD). However, limited data are available about the prevalence of dyslipidemias related to LDL-C, HDL-C, and TGs among French patients treated with lipid-lowering agents. This paper describes the prevalence of various types of dyslipidemias among patients treated with lipid-lowering agents in French general practice. This was a cross-sectional, observational study conducted using retrospective data collection at the time of enrollment. Eligible patients were those treated pharmacologically for dyslipidemia in the Cegedim Strategic Data general practice network. Fasting lipid values and cardiovascular (CV) risk factors were gathered by investigators using an ad hoc questionnaire. European guidelines were used to define various types of dyslipidemias. Polytomous logistic regression was used to assess the associations between different dyslipidemias and diabetes mellitus, a history of CHD, and the number of CV risk factors. A total of 946 patients had a complete lipid profile and valid data for determining CV risk status. The mean (SD) age of these patients was 64.0 (9.9) years, and 55.7% of the patients were men. At least 1 abnormality in LDL-C, HDL-C, or TGs was present in 791 (83.6 %) of the 946 patients. The rates of elevated LDL-C, low HDL-C, and elevated TGs were 73.2%, 16.9%, and 30.3%, respectively (these groups are not mutually exclusive). Among those who did not reach the LDL-C goal, 38.7% had dyslipidemias with low HDL-C, elevated TGs, or both. Compared with having a normal lipid profile, each additional CV risk factor increased the likelihood of the following types of dyslipidemias: low HDL-C and/or elevated TGs, but normal LDL-C (odds ratio [OR], 1.36; 95% CI, 1.03-1.79); elevated LDL-C and TGs, but normal HDL-C (OR, 1.58; 95% CI, 1.24-2.02); and all 3 lipid abnormalities (OR, 1.54; 95% CI, 1.10-2.14). Patients with diabetes had a similarly increased risk of mixed dyslipidemias, whereas patients with a history of CHD did not. Among these patients treated with lipid-lowering agents, 38.7% had mixed dyslipidemias, including low HDL-C, elevated TGs, both low HDL-C and elevated TGs, or all 3 lipid abnormalities. Patients with a greater number of nonlipid CV risk factors or with diabetes had a significantly increased risk of mixed dyslipidemias involving elevated TGs and/or low HDL-C in addition to elevated LDL-C.


Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly(lactide-co-glycolide) microspheres.
We have assessed the biocompatibility of a new composite bone graft consisting of calcium phosphate cement (CPC) and poly(lactide-co-glycolide) (PLGA) microspheres (approximate diameter of 0.18-0.36 mm) using cell culture techniques. CPC powder is mixed with PLGA microspheres and water to yield a workable paste that could be sculpted to fit the contours of a wound. The cement then hardens into a matrix of hydroxyapatite microcrystals containing PLGA microspheres. The rationale for this design is that the microspheres will initially stabilize the graft but can then degrade to leave behind macropores for colonization by osteoblasts. The CPC matrix could then be resorbed and replaced with new bone. In the present study, osteoblast-like cells (MC3T3-E1 cells) were seeded onto graft specimens and evaluated with fluorescence microscopy, environmental scanning electron microscopy and the Wst-1 assay (an enzymatic assay for mitochondrial dehydrogenase activity). Cells were able to adhere, attain a normal morphology, proliferate and remain viable when cultured on the new composite graft (CPC-PLGA) or on a control graft (CPC alone). These results suggest that our new cement consisting of CPC and PLGA microspheres is biocompatible. This is the first time that a 'polymer-in-mineral' (PLGA microspheres dispersed in a CPC matrix) cement has been formulated that is moldable, resorbable and that can form macropores after the cement has set.


[Heritability of body weight and fork length for Oncorhynchus masou masou].
Body weight and body length have been considered as the most important production traits for the fish genetic improvement. For cold-water fish, body length was usually substituted by fork length. In order to estimate the heritability of body weight and fork length of the sixth generation Oncorhynchus masou masou, which was introduced into China, the method of unbalanced nest design and an artificial insemination technigue were used. Twenty-nine full-sib families and fourteen half-sib families were obtained. Body weight and fork length of O. masou masou were measured in 12 and 24 months after fertilization. Based on full-sib and half-sib families data, the causal components of phenotypic variance were calculated. The results showed that, (1) during the whole growth phase of O. masou masou, the coefficient variation (CV) of fork length was higher than body weight, and CV of 12-month old was higher than that of 24-month old; (2) body weight and fork length of O. masou masou among sires and dams among sires were significant difference (P<0.01) both at 12 months and at 24 months; (3) the maternal component estimates were significantly larger than those of paternal ones for body weight and fork length traits both at 12 months and at 24 months; (4) for 12 months of O. masou masou the heritabilities of body weight and fork length were 0.41~0.51 and 0.46~0.54, respectively. For 24 months the values were 0.55~0.60 and 0.53~0.59, respectively; and (5) it was concluded that the heritability of growth traits in O. masou masou was relatively high and this highlights the potential to improve its growth through selective breeding. This study shows important data supporting for further genetic improvement of O. masou masou.


COG complexes form spatial landmarks for distinct SNARE complexes.
Vesicular tethers and SNAREs (soluble N-ethylmalemide-sensitive fusion attachment protein receptors) are two key protein components of the intracellular membrane-trafficking machinery. The conserved oligomeric Golgi (COG) complex has been implicated in the tethering of retrograde intra-Golgi vesicles. Here, using yeast two-hybrid and co-immunoprecipitation approaches, we show that three COG subunits, namely COG4, 6 and 8, are capable of interacting with defined Golgi SNAREs, namely STX5, STX6, STX16, GS27 and SNAP29. Comparative analysis of COG8-STX16 and COG4-STX5 interactions by a COG-based mitochondrial relocalization assay reveals that the COG8 and COG4 proteins initiate the formation of two different tethering platforms that can facilitate the redirection of two populations of Golgi transport intermediates to the mitochondrial vicinity. Our results uncover a role for COG sub-complexes in defining the specificity of vesicular sorting within the Golgi.