Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.
Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.


Squamous cell carcinoma of the scrotum.
A patient with psoriasis was found to have a large mass on his scrotum. He was at increased risk for the occurrence of skin cancer, both from the treatments he received for control of his psoriasis and from previous occupational exposure. We present his case and review the risk factors involved.


"A Song of Ice and Fire"-another verse from the world of ablation.
The debate between the use of radiofrequency (RF) or cryoenergy for ablation near the atrioventricular (AV) conducting system or small coronaries has been fueled by the relative efficacies and risks of the two technologies, particularly in smaller hearts. The manuscript by Schneider et al adds another chapter to that ongoing debate.


Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany.
Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.


Serological and biochemical characterization of surface antigen expressed on human myeloid cells and identification of six distinct antigen systems.
Six distinct surface antigens selectively expressed on human myeloid cells were defined with ten murine monoclonal antibodies. Four antigens (GAp95, GAp170, GAp160-220, GAp145-200) are expressed on protein molecules and one antigen (GANGL) is detected in neutral glycolipids. The biochemical nature of the remaining one (GA8.9) is unknown. GAp95 and GANGL are expressed on relatively mature myeloid cells, whereas GAp160-220 is expressed on immature myeloid cells. GAp170 and GAp145-200 are expressed on a wide range of myeloid cells. GA8.9 was found on NKM-1, a cell line of acute myelomonocytic leukemia, and also on some acute nonlymphocytic leukemia cells.


Novel oleyl amine-modified polymannuronic acid micelle loading tacrolimus for therapy of allergic conjunctivitis.
Marine polysaccharide-based nanomaterial attracted considerable attention due to its biocompatibility and biodegradability. Here, a novel polymannuronic acid derivative (PM-C18) was synthesized as nanocarrier modified with hydrophobic oleyl amine. Its structure was confirmed by Fourier-transformed infrared spectrometry and nuclear magnetic resonance. To investigate its function, we developed tacrolimus (FK506) loaded nanoparticle by self-assembling PM-C18 and studied its drug loading, cytotoxicity and mechanism of in vitro release. Furthermore, we established a mouse model of allergic conjunctivitis (AC) to evaluate the efficacy of FK506 loaded PM-C18. The results indicated that PM-C18 carrier can encapsule FK506 with high drug loading (18%) and average particle size of 110.34±1.6nm. The release mechanism was diffusion initially followed a lasting release induced by swelling and collapse of PM-C18. One-week treatment with FK506 loaded PM-C18 efficiently relieved the symptoms of AC, which indicated it could serve as a potential ophthalmic drug for patients with AC. Compared with FK506 ophthalmic suspension, FK506 loaded PM-C18 improved medication adherence. Most importantly, we developed a novel versatile nanomaterial of PM-C18 which could encapsule other active agents for more applications.


Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings.
The response to treatment and risk factors for early mortality following initiation of combination antiretrovirals(ARVs) in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating ARVs in 12 clinical centers in Mozambique, Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received ARVs for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load 400 copies/ml, and 38% had a CD4 cell count >200/microl. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of HAART 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low BMI, low hemoglobin levels, and CD4 values <200 cells/microl at baseline. Mortality rates following initiation of HAART are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation.HAART initiated at higher CD4 cell count levels, especially among malnourished and/or anemic patients, will carry significant public health impact.


[The effectiveness of non-invasive lung ventilation in lateral amyotrophic sclerosis].
Lateral amyotrophic sclerosis (LAS) is a very severe neurodegenerative disease with progressive course and terminal respiratory insufficiency. Non-invasive lung ventilation (NLV) is a main method of treatment. We studied the effectiveness of NLV in LAS and assessed patient's adaptation to NLV, life expectancy, compliance and an effect of NLV on spirometric parameters. NVL was administered to 28 patients, mean age 56.2 ± 9.4 years, including 10 patients with bulbar onset and 16 with spinal onset. The rapid progression of the disease was observed in 15 patients, slow progression in 13 patients. NLV used in regime S extended the life of patients, in particular, patients with spinal onset. The adjustment to the NLV device plays a crucial role. Two types of the adjustment were established: gradual (13 patients) and accelerated (4 patients). The causes of the latter were not found. It should be emphasized that several questions related to the details of NVL regime should be specified in further research in the field.


[Activate vitamin D3 or bisphosphonate in glucocorticoid-induced osteoporosis].
Glucocorticoid therapy is associated with bone loss starting soon after the therapy is initiated and an increased risk of fracture. Activated forms of vitamin D(3), which are frequently prescribed for postmenopausal osteoporosis in Japan, are one of a useful agent to prevent glucocorticoid-induced osteoporosis. In this review, the effect of activate form vitamin D(3) is compared with plain vitamin D or bisphosphonate.


The good practitioner: the story of Brent L. Benkelman.
Dr Brent Benkelman has practiced oral surgery in Manhattan, Kansas, since 1971. Having grown up in a tiny farming town in western Kansas, he opted for the lifestyle of a smaller community after graduating from the University of Missouri at Kansas City School of Dentistry in 1966 and completing his training in oral and maxillofacial surgery in 1969. His experiences since then have revolved around family, practice, and community. With his family as his first priority, he has participated in various community activities, including a church-operated food pantry, an emergency shelter for the homeless, and Habitat for Humanity. He was nominated as a moral exemplar in dentistry for his dedicated commitment to his patients and because he understands and cares about the complexities of his patients as human beings, placing his own financial gain secondary to the interests of his patients.


Cell type-specific quantitative predictions of radiation-induced chromosome aberrations: a computer model approach.
A quantitative computer model was applied to simulate the three-dimensional (3D) spatial organization of chromatin in human cell nuclei under defined conditions of virtual irradiation to explore the implications of spatial organization on chromosome aberrations. To calibrate the virtual irradiation algorithm, a dose-dependent spectrum of radiation-induced chromosome aberrations such as dicentrics, translocations and centric rings was calculated for low-LET radiation doses ranging from 0.5 to 5 Gy. This was compared with the results from experimental studies. While the dose-response curves calculated from model simulations agree well with experimental dose-response curves for dicentrics and translocations, centric rings are significantly more frequent in the model simulation than in experiments despite taking into account exclusive arm territories in the applied Spherical 1 Mbp Chromatin Domain (SCD) computer model explicitly. Taking into account the non-random positioning of chromosome territories observed in lymphocyte cell nuclei (a so-called gene density-correlated arrangement of chromosome territories), aberration frequencies were calculated with the calibrated irradiation algorithm to investigate the impact of chromosome territory neighborhood effects (proximity effects). The absolute frequencies of pairwise exchanges agree well with those found in an experimental study. In conclusion, the results obtained using the computer model approach presented here based on only a few adjustable parameters correlated well with those of experimental studies of chromosome aberration frequencies. Thus the model may be a useful tool in radiation-induced cancer risk estimates in combination with epidemiological studies.


Biaxial elastic properties of rat arteries in vivo: influence of vascular wall cells on anisotropy.
There is no consensus as to the degree of arterial anisotropy or to its relationship to vascular cell function. Given the relevance of the isotropic assumption in formulating elasticity models, reliable measures of biaxial displacements are needed. In this study, a video motion analyzer (VMA) was used to describe the biaxial in vivo dynamic elasticity of 22 carotid arteries and 5 abdominal aortas in 27 rats. The influence of vascular cell function was also examined by subjecting six rats to a photosensitive drug, chloroaluminum sulfonated phthalocyanine (CASPc), which is focally cytotoxic on activation by laser. Circumferential compliance (Ccirc) was greater than longitudinal compliance (Clong) for all vessels. Compliance pressure curves were nonlinear, and biaxial displacements were in phase. The circumferential elastic modulus was less than the longitudinal modulus at common stresses. CASPc + laser reduced Ccirc but not Clong, thus altering Poisson's ratio. In conclusion, rat arteries are biaxially, nonlinearly elastic and anisotropic in vivo. Vascular cells modulate Poisson's ratio by influencing Ccirc.


Multicentre evaluation of a rule-based data filter for home monitoring of implanted cardioverter defibrillators.
We developed a rule-based data filter for the automatic interpretation of data transmitted from implantable cardioverter defibrillators (ICDs). The feasibility and user acceptability of the data filter were tested in a multicentre study. Fifteen European centres analysed 10 cases each. The cases represented ICD follow-up findings, e.g. new tachycardia, battery depletion or sensing defects. The mean follow-up period was 68 days (SD 35). A questionnaire was used to collect information regarding the functionality and general concept of automatic data interpretation. A score of five or above (range 1-9) was classified as acceptable. According to the questionnaires, there was a high degree of satisfaction with the general concept of automatic data interpretation (mean 6.7, SD 1.2) and with user guidance (mean 7.1, SD 0.8). Safety (mean 7.0, SD 1.4) and accuracy (mean 6.7, SD 1.4) of the evaluation of device-related and clinical problems were regarded as high. Support in daily routine was considered to be high (mean 7.3, SD 1.1) as the system was easy to understand (mean 7.5, SD 0.9). The results indicated a high user acceptance with easy system handling.


Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population.
Hereditary hemochromatosis (HH) is one of the most common autosomal recessive genetic disorders of iron metabolism in white populations, which leads to inappropriately high iron absorption. C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE). In the present study, C282Y, H63D, and S65C mutations in 395 normal Chinese Han populations from Zhejiang province were investigated. No C282Y, S65C mutations, and H63D homozygote was observed, while the genotype frequency of H63D heterozygote was 4.6% and the allelic frequency 2.3% in this population. This was the first report to analyze the prevalence of C282Y, H63D, and S65C mutations in the HFE gene in a Chinese Han population. Low incidence of the HFE gene mutations could be a reason for the rarity of HH in the Chinese Han population studied.


Effect of Lactobacillus rhamnosus GG in persistent diarrhea in Indian children: a randomized controlled trial.
To evaluate the role of Lactobacillus rhamnosus GG (LGG) as probiotic in persistent diarrhea (PD) in children of North Bengal, India. Hospital-based study. Randomized, double-blind controlled trial. All patients of PD admitted over a period of 2 years were included in the study as per predefined inclusion criteria. They were randomized to receive oral rehydration solution (ORS) alone, or ORS plus LGG powder containing 60 million cells, twice daily for a minimum period of 7 days or till diarrhea has stopped along with correction of dehydration with ORS and/or intravenous fluids as per WHO protocol and antibiotics in culture positive patients. The duration and frequency of purge and vomiting were studied. Data were analyzed by SPSS-10 software. Statistical significance was calculated by Student t test and chi2 test. The study comprised of 235 patients randomized into 2 groups, cases (117) and controls (118). Both the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and distribution of infections. Stool culture was positive in 90 (38.3%) patients, Escherichia coli being the commonest organism followed by Shigella spp. and Clostridium difficile. The mean duration of diarrhea was significantly lower in the cases than in controls (5.3 vs. 9.2 d). The average duration of hospital stay was also significantly lesser in cases. No complication was observed from the dose of LGG used. LGG (dose of 60 million cells) could decrease the frequency and duration of diarrhea and vomiting and reduced hospital stay in patients of PD.


Disorders of water imbalance.
Disorders of water imbalance manifest as hyponatremia and hypernatremia. To diagnose these disorders, emergency physicians must maintain a high index of suspicion, especially in the high-risk patient, because clinical presentations may be nonspecific. With severe water imbalance, inappropriate fluid resuscitation in the emergency department may have devastating neurological consequences. The rate of serum sodium concentration correction should be monitored closely to avoid osmotic demyelination syndrome in hyponatremic patients and cerebral edema in hypernatremic patients.


Relationships of Schistosoma haematobium, hookworm and malarial infections and metrifonate treatment to growth of Kenyan school children.
Relationships of S. haematobium, hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth, S. haematobium and hookworm were common and malaria was endemic. All children with light-moderate S. haematobium infections (1-500 eggs/10 ml adj) in 4 schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 201) groups, treated, and examined again 6 months later (Exam 2). An additional 19 heavily infected children (HIT group greater than 500 eggs/10 ml adj) were treated immediately after Exam 1 and also followed. The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group. The MIT group gained significantly (P less than 0.001) more than the MIP group in weight (0.8 kg), percent weight for age (2.3 percentage points), weight for height squared (0.04 units), arm circumference (0.4 cm), percent arm circumference for age (1.7 percentage points) and in triceps and subscapular skinfold thicknesses. In addition, the placebo group showed statistically significant decreases between exams in percentage weight for age, percent arm circumference for age, both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Characteristic scales of optical field depolarization and decorrelation for multiple scattering media and tissues.
Decorrelation and depolarization properties of multiply scattering media and tissues in the case of propagation of coherent probe beams are analyzed in terms of photon path distribution. A specific correlation time determining the relationship between correlation and polarization states of scattered optical fields is introduced. Results of correlation and polarization experiments with phantom scatterers (such as water suspensions of polystyrene spheres) and tissues with controlled optical properties (such as the human sclera) are presented. © 1999 Society of Photo-Optical Instrumentation Engineers.


Preparation of monoclonal antibody against HPT and its application to detecting marker protein in genetically modified rice.
To produce the monoclonal antibodies (mAbs) against hygromycin B phosphotransferase (HPT) and to develop immunoassay based on mAbs for biosafety assessment of HPT in genetically modified rice (GM rice). BALB/c mice were immunized with purified recombinant 6His. HPT protein, and the conventional hybridoma technology was used to generate the monoclonal hybridoma cells. ELISA and Western blot were used to analyze the specificity of mAbs recognizing HPT and the cross reaction with other proteins. A double-Ab sandwich ELISA method was established to detect HPT expression level in the sck gene-modified rice plants. Four hybridomas, named F1, D4-2, D4-4, and D4-5, producing the mAbs against HPT were successfully obtained with the titer of ascetic mAbs ranging from 1x10(-4) to 1x10(-5). Identification of subclass showed that all the produced mAbs belonged to IgG1. Western blot showed specific binding reaction between the mAbs to the HPT proteins expressed in the GM rice. A double sandwich ELISA coated with anti-HPT polyclonal antibody was established with mAbs as sandwich antibody, which showed a sensitivity of 30ng/mL and did not crossreact with other proteins. The expression level of HPT in the leaves of sck-transformed lines was detected (80-150ng/mL). But HPT protein in the grain and seed of GM rice could not be detected using this ELISA assay. Anti-HPT mAbs prepared herein have a high specificity and can be used for rapid assay of HPT antigen. The expression level of HPT in the GM rice grain and seed is lower than our ELISA detection limit.


Multiple intragastric treatment versus continuous administration via the diet. Comparative pharmacokinetics of abecarnil in mouse.
1. Abecarnil was administered to female mice at doses of 5, 50 and 150 mg/kg per day for 4 weeks either intragastrically once a day or was offered continuously via the diet. 2. On days 1, 7, 14 and 28 plasma level profiles (0-24 h) were determined in identical groups of animals. Additionally, faecal excretion of abecarnil and distribution in brain, liver and kidney was measured. 3. Drug administration via the diet was characterized by: (a) a circadian rhythm of concentrations with highs at night and lows during the day; (b) a dose-proportional increase in AUC and mean plasma levels; (c) slight accumulation in the plasma after the two higher doses. 4. Intragastric treatment resulted in: (a) clearly distinguishable absorption and disposition phases in the plasma with prominent peaks; (b) slight accumulation at the two higher doses; (c) dose-proportionality for the 50 and 150 mg/kg doses. 5. Drug load after the two routes of administration was different resulting in four times higher peak plasma levels and in double AUC values after intragastric administration than after the diet.


Photophysics of dopamine-modified quantum dots and effects on biological systems.
Semiconductor quantum dots (QDs) have been widely used for fluorescent labelling. However, their ability to transfer electrons and holes to biomolecules leads to spectral changes and effects on living systems that have yet to be exploited. Here we report the first cell-based biosensor based on electron transfer between a small molecule (the neurotransmitter dopamine) and CdSe/ZnS QDs. QD-dopamine conjugates label living cells in a redox-sensitive pattern: under reducing conditions, fluorescence is only seen in the cell periphery and lysosomes. As the cell becomes more oxidizing, QD labelling appears in the perinuclear region, including in or on mitochondria. With the most-oxidizing cellular conditions, QD labelling throughout the cell is seen. Phototoxicity results from the creation of singlet oxygen, and can be reduced with antioxidants. This work suggests methods for the creation of phototoxic drugs and for redox-specific fluorescent labelling that are generalizable to any QD conjugated to an electron donor.


Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study.
High homocysteine level is a risk factor for atherosclerosis and has been associated with lacunar infarcts (LIs), white matter lesions (WML) and cognitive dysfunction. It is unclear whether homocysteine is associated with cerebral small vessel disease (cSVD) on top of pre-existent atherosclerosis. We evaluated the association between homocysteine and cSVD in a large cohort of patients with symptomatic atherosclerotic disease. Within the SMART-MR study, a prospective cohort study of patients with symptomatic atherosclerotic disease, we estimated cross-sectional associations of total plasma homocysteine (THCY) and hyperhomocysteinemia (HHCY) with WML volume and presence of LI, using automated brain segmentation in MRIs of 1232 patients and cognitive function in 763 patients. WML were expressed as a logarithmic transformed percentage of total brain volume. Linear regression analyses adjusted for age, sex, vascular risk factors and extent of atherosclerosis showed that THCY and HHCY were significantly associated with larger WML volumes (B=0.01%: 95% CI 0.002-0.02%, and B=0.21%: 95% CI 0.04-0.39%). Increasing THCY was significantly associated with an increased risk of LIs (OR 1.04, 95% CI 1.01-1.07, per 1 μmol). Moreover, HHCY was associated with worse cognitive function (B=-0.12: 95% CI -0.22 to -0.01). In patients with symptomatic atherosclerotic disease, higher homocysteine levels are associated with higher WML volume, presence of LI and slightly worse cognitive function.


Aminoglycoside nephrotoxicity: comparative assessment in critically ill patients.
In a prospective trial to determine the incidence of nephrotoxicity with each of three aminoglycoside antibiotics, adults in intensive care units with presumed or proven bacterial infections were treated with intravenous gentamicin, tobramycin, or amikacin. Treatment groups were similar with respect to age, other medical disorders, type of infection, duration of aminoglycoside therapy, additional antibiotics used, other drugs prescribed (notably diuretics and corticosteroids), and rate of superinfection. Nephrotoxicity occurred with gentamicin during 44/121 (36.3%) treatment courses, with tobramycin during 21/92 (22.8%) courses, and with amikacin during 4/16 (25.0%) courses. Although frequent, nephrotoxicity reversed after treatment stopped. Tobramycin nephrotoxicity occurred significantly less often than did gentamicin nephrotoxicity (p less than 0.05). The relative safety of tobramycin may result from lower tissue accumulation during therapy.


Pneumotonometer Accuracy Using Manometric Measurements after Radial Keratotomy, Clear Corneal Incisions and Lamellar Dissection in Porcine Eyes.
Purpose/Aim of the study: Measured intraocular pressure (IOP) after corneal incisions may not be reflective of the true IOP because of changes in corneal biomechanical properties. The purpose of this study is to investigate the effect of various corneal incisions on pneumotonometer accuracy in enucleated porcine eyes.Materials and Methods: A pneumotonometer was used to measure IOP (IOPp) at manometrically controlled pressure levels of 10, 20, 30 and 40 mmHg in enucleated porcine eyes. IOP measurements at each level were repeated after one of the following corneal incisions: radial keratotomy (8 eyes), lamellar dissection (10 eyes), clear cornea standard phacoemulsification incisions (10 eyes). The pneumotonometer error, defined as the difference between IOPp and manometric pressure (IOPm), was calculated for each pressure level. The error before the corneal incisions was compared to the error after the corneal incisions to assess the accuracy of the pneumotonometer.Results: The pneumotonometer underestimates true IOP at all pressure levels, both before and after the corneal procedures. There was a statistically significant greater underestimation of IOP after radial keratotomy incisions at pressure levels of 20, 30 and 40 mmHg (p = .013, 0.004, and 0.002, respectively). There was no statistically significant difference in the amount of pneumotonometer underestimation error after lamellar dissection or standard cataract incisions.Conclusion: The pneumotonometer underestimates true IOP in enucleated porcine eyes at all pressure levels between 10-40 mmHg. Radial keratotomy incisions caused a statistically significant greater underestimation error in pneumotonometry measurements at pressures of 20-40 mmHg. Lamellar dissection and clear corneal cataract incisions did not cause an additional error in pneumotonometry measurements in enucleated porcine eyes.


Involvement of neutrophils in thrombus formation in living mice.
Thrombosis is one of the major causes of human death worldwide. Identification of the cellular and molecular mechanisms leading to thrombus formation is thus crucial for the understanding of the thrombotic process. To examine thrombus formation in a living mouse, new technologies have been developed. Digital intravital microscopy allows to visualize the development of thrombosis and generation of fibrin in real-time within living animal in a physiological context. This specific system allowed the identification of new cellular partners involved in platelet adhesion and activation. Furthermore, it improved, especially, the knowledge of the early phase of thrombus formation and fibrin generation in vivo. Until now, platelets used to be considered the sole central player in thrombus generation. However, recently, it has been demonstrated that leukocytes, particularly neutrophils, play a crucial role in the activation of the blood coagulation cascade leading to thrombosis. In this review, we summarized the mechanisms leading to thrombus formation in the microcirculation according to the method of injury in mice with a special focus on the new identified roles of neutrophils in this process.


Corrected Article: Simulation and observation of line-slip structures in columnar structures of soft spheres [Phys. Rev. E 96, 012610 (2017)].
This corrects the article DOI: 10.1103/PhysRevE.96.012610.


[Surgical lung biopsy for interstital lung diseases: complications, diagnostic yield and mortality].
We retrospectively reviewed 110 consecutive patients with interstitial lung diseases (ILDs) who underwent surgical lung biopsy over 13 years from 1989-2002. Surgical procedures, medical records, surgical complications and outcome including post-operative exacerbation of ILDs were assessed in order to clarify the safety and efficacy of surgical lung biopsy. Forty-one patients underwent open lung biopsy (OLB), while 69 patients received videothoracoscopic lung biopsy (VTLB). There was no significant difference in patient characteristics, pulmonary function, arterial oxygen pressure and therapy prior to surgery between the two groups. The mean number of biopsy specimens was 2.5. Left side was selected as the site of biopsy in 70 cases. Duration of surgery was not significantly different between 2 groups. Bleeding during operation was less in the VTLB group than in the OLB group, although the mean bleeding amount was only 16.5mL. The duration of thoracic drainage and length of hospital stay were shorter in the VTLB group. The overall rate of surgical complications was 10.9%, with no difference between the two groups. The overall 30-day post-SLB mortality was 6.4% and majority of these had a very poor prognosis pathologically. The diagnostic yield of all 110 cases was 98.2%. SLB is a relatively safe and efficient diagnostic method in the diagnosis of ILDs.


Acetabular fracture in a 16-year-old secondary to an all-terrain vehicle accident.
All-terrain vehicles have been associated with a large number of injuries in the pediatric age group. Despite strict regulations governing the sale and manufacture of these vehicles, they continue to be in widespread use. We report a case of a 16-year-old boy with an acetabular fracture secondary to being thrown from an all-terrain vehicle. Acetabular fractures are rare in the pediatric population and are most commonly associated with motor vehicle accidents and other high-energy trauma. Although the diagnosis is straightforward, delayed presentation is not uncommon.


Association between angiotensin-1 converting enzyme gene polymorphism and the metabolic syndrome in a Mexican population.
Metabolic Syndrome (MS) is recognized as a cluster of cardiovascular risk factors. All components of MS have a genetic base. Genes of the renin angiotensin system are potential candidate genes for MS. We investigated whether angiotensin converting enzyme (ACE) gene polymorphism increases susceptibility to MS as an entity in a Mexican population. In a cross-sectional study, 514 individuals were studied including 245 patients with MS and 269 subjects without MS criteria. ACE gene polymorphism was detected using PCR. MS was defined according to The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria, except that the raised fasting plasma glucose <or=100 mg/dl criterion for identification of intolerance fasting glucose was modified in accordance with the suggestion of the American Diabetes Association. Patients with MS were significantly different from subjects without MS in relation to mean body mass index (BMI), waist circumference (WC), systolic blood pressure, diastolic blood pressure, glucose, total cholesterol (C), triglycerides, HDL-C, and LDL-C (P<0.0001). The differences in the mean BMI, WC, glucose, total cholesterol, triglycerides, LDL-C, and HDL-C were maintained in patients with the MS and DD genotypes (P<0.01). The DD genotype was strongly associated with MS (adjusted OR=5.48, 95% CI 3.20-9.38, P<0.0001). We concluded that the DD genotype increases susceptibility to MS in a Mexican population. These results indicate that pharmacological and non-pharmacological treatment and a reduction in body fat will have important therapeutic implications in this disease.


Plk1 controls the Nek2A-PP1γ antagonism in centrosome disjunction.
In human cells, separation of the centrosomes and formation of a bipolar spindle are essential for correct chromosome segregation [1]. During interphase, centrosomes are joined together by the linker proteins C-Nap1 and rootletin [2-4]. At the onset of mitosis, these linker proteins are phosphorylated and displaced from centrosomes by the Nek2A kinase, which is regulated by two Hippo pathway components, Mst2 kinase and the scaffold protein hSav1. The kinesin-5 motor protein Eg5 promotes centrosome separation in a parallel pathway to Nek2A [5]. Here, we report that Polo-like kinase 1 (Plk1) functions upstream of the Mst2-Nek2A kinase module in centrosome disjunction as well as being important for Eg5 localization at centrosomes. Plk1 regulates Mst2-Nek2A-induced centrosome disjunction by phosphorylating Mst2. The absence of Plk1 phosphorylation of Mst2 promotes assembly of Nek2A-PP1γ-Mst2 complexes, in which PP1γ counteracts Nek2A kinase activity. In contrast, Plk1 phosphorylation of Mst2 prevents PP1γ binding to Mst2-Nek2A, allowing Nek2A activity to promote centrosome disjunction. We propose that centrosome disjunction is regulated by Plk1, providing a well-balanced control between the counteracting Nek2A and PP1γ activities on the centrosome linker.


In vitro tetracycline labelling and bone cell survival in human trabecular bone explants.
Results are presented which document the feasibility and utility of human trabecular bone explants for in vitro bone research. This approach is advantageous because it allows bone cells to maintain their natural orientation on the endosteal surface, and keeps surrounding marrow intact--thus retaining the immediate local microenvironment. In addition, bone cells are not exposed to transient, but sometimes harsh, isolation procedures. Data are presented which show greater initial bone cell numbers from younger donors and the change in these numbers over culture periods up to 21 days. A technique is presented which achieves single and double tetracycline label incorporation into the mineralizing front of bone explants in vitro using a pulse-chase methodology.


A gene transcription signature of obesity in breast cancer.
Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of 103 tumors for which the patients' body mass index (BMI) was ascertained. Sample profiles were stratified according to patients' obesity phenotype defined as normal (BMI < 25), overweight (BMI 25-29.9), or obese (BMI ≥ 30). Widespread gene expression alterations were evident in breast tumors from obese patients as compared to other tumors, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. In multiple public expression data sets of breast cancers (representing > 1,500 patients), manifestation of the obesity signature patterns correlated with manifestation of a gene signature for IGF signaling and (to a lesser extent) with lower levels of estrogen receptor. In one patient cohort, manifestation of the obesity signature correlated with shorter time to metastases. A number of small molecules either induced or suppressed the obesity-associated transcriptional program in vitro; estrogens alpha-estradiol, levonorgestrel, and hexestrol induced the program, while several anti-parkinsonian agents targeting neurotransmitter receptor pathways repressed the program. Obesity in breast cancer patients appears to impact the gene expression patterns of the tumor (perhaps as a result of altered body chemistry). These results warrant further investigation of obesity-associated modifiers of breast cancer risk and disease outcome.


Craniosynostosis: an analysis of the timing, treatment, and complications in 164 consecutive patients.
Treatment options for the craniosynostoses vary from conservative observation until completion of growth to radical remodeling in infancy. To further define the timing and type of treatment necessary in these complex disorders, we have retrospectively analyzed all patients operated on for this deformity during the past 12 years. One-hundred and sixty-four patients with craniosynostosis were analyzed and subgrouped into asymmetrical (predominantly unilateral) and symmetrical (bilateral) deformities, in addition to segregation by age and type of procedure performed. This was done recognizing that no deformity, like no normal human face, is truly symmetrical. Results of treatment were categorized on the basis of the need for additional surgery and varied from no refinements necessary (category I) to major reduplication of the initial procedure (category IV). Analysis of the data led us to conclude that excellent results can be expected in the asymmetrical deformities group treated in infancy by a unilateral approach. Similarly, for the mild symmetrical deformities, treatment at this time by bilateral orbital advancement gives satisfactory results in the majority of patients. By contrast, the more severe symmetrical groups treated in childhood have a high incidence of requiring secondary major reconstructions, and consideration should be given to delaying craniofacial surgery until age 7 or older, although earlier cranial surgery may be advisable.


Characterization of the Individual Short-Term Frequency Stability of Cryogenic Sapphire Oscillators at the 10(-16) Level.
We present the characterization of three cryogenic sapphire oscillators (CSOs) using the three-cornered-hat method. Easily implemented with commercial components and instruments, this method reveals itself very useful to analyze the fractional frequency stability limitations of these state-of-the-art ultrastable oscillators. The best unit presents a fractional frequency stability better than 5 ×10(-16) at 1 s and below 2 ×10(-16) for [Formula: see text].


Studies on the pituitary "Fettstoffwechselhormon". VIII. Radioimmunoassay of the lipolytic factor P-LF II D.
A radioimmunoassay of the lipolytic peptide P-LF II D from porcine pituitaries is described. The assay is performed with 125-iodine labeled P-LF II D and with antisera either from guinea pigs or from rabbits. Bound antigen is separated from the free by double antibody technique. No cross reaction is observed with gamma lipotropin, peptide B, secretin, glucagon, isoproterenol. Due to contamination P-LF II C, beta lipotropin and human growth hormone displace the tracer when added at large doses. Complete cross reaction is observed between porcine 1-39 ACTH and P-LF II D. Specificity of this reaction is demonstrated by the increase of cross reaction, when ACTH fragments of increasing length of the polypeptide chain are used (1-23 ACTH, 1-24 ACTH and 1-28 ACTH).


Non-medical prescription opioid users exhibit dysfunctional physiological stress responses to social rejection.
Non-medical prescription opioid use (NMPOU) recently increased dramatically, especially in the U.S. Although chronic opioid use is commonly accompanied by deficits in social functioning and dysregulation of the hypothalamic-pituitary adrenergic (HPA) stress axis, little is known about the impact of NMPOU on psychosocial stress responses. Therefore, we measured physiological responses of the autonomic nervous system and the HPA axis to social rejection using the Cyberball paradigm. We compared 23 individuals with NMPOU, objectively confirmed by hair and urine analyses, with 29 opioid-naïve, healthy controls. As expected, heart rate variability (HRV), an index of parasympathetic activity, increased significantly during exclusion within controls, while in the NMPOU group only a trend in the same direction was found. However, increased HRV was robustly moderated by opioid craving indicating worse emotion regulation to social exclusion specifically in individuals with high opioid craving. Greater levels of the adrenocorticotropic hormone and cortisol responses to social rejection were found in the NMPOU group indicating hyperreactivity of the HPA axis to social exclusion. Self-ratings suggest that opioid users were aware of rejection, but less emotionally affected by exclusion. Furthermore, controls showed greater negative mood after the Cyberball confirming the task's validity. Moreover, NMPOU individuals reported a smaller social network size compared to controls. Present findings suggest that chronic NMPOU is associated with dysfunctional physiological responses to psychosocial stressors such as social rejection. In sum, NMPOU was associated with poorer regulation of the parasympathetic nervous system, especially under opioid craving highlighting its potential importance in relapse prevention.


A robotic system for quantitative assessment and poststroke training of forelimb retraction in mice.
Neurorehabilitation protocols based on the use of robotic devices have recently shown to provide promising clinical results. However, their efficacy is still limited because of the poor comprehension of the mechanisms at the basis of functional enhancements. To increase basic understanding of robot-mediated neurorehabilitation by performing experiments on a rodent model of stroke. Mice were trained to pull back a handle on a robotic platform and their performances in the task were evaluated before and after a focal cortical ischemic stroke. The platform was designed for the quantitative assessment of forelimb function via a series of parameters (time needed to complete the task, t-target; average force; number of sub-movements). The animals rapidly learned the retraction task and reached asymptotic performance by the fifth session of training. Within 2 to 6 days after a small, endothelin-1-induced lesion in the caudal forelimb area, mice showed an increase in t-target and number of sub-movements and a corresponding decrease in the average force exerted. These parameters returned to baseline, pre-lesion values with continued platform training (10-14 days after stroke). These results highlight the utility of the devised platform for characterizing post-infarct deficits and improvements of forelimb performance. Further research is warranted to widen the understanding of device-dependent rehabilitation effects.


An evaluation of adi agbon as a clearing agent in paraffin processing of embryonic tissues--preliminary report.
Adi agbon, an oily extract of the endosperm of the coconut fruit (Cocoa nucifera, L.) was investigated as a clearing agent for embryonic soft tissues. Paraffin sections stained with haematoxylin an eosin revealed normal tissue architecture and light microscopic details were easily identified. However, some tissue shrinkage was observed, particularly in the brain. As prepared for this study, this locally available compound is useful for routine work but appears unsuitable for quantitative histological studies.


In depth analysis of apoptosis induced by silica coated manganese oxide nanoparticles in vitro.
Manganese oxide nanoparticles (MnO NPs) have been regarded as a new class of T1-positive contrast agents. The cytotoxicity of silica coated MnO NPs (MnO@SiO2 NPs) was investigated in human cervical carcinoma cells (HeLa) and mouse fibroblast cells (L929). The changes of cell viability, cell morphology, cellular oxidative stress, mitochondrial membrane potential and cell cycle induced by MnO@SiO2 NPs were evaluated. Compared to HeLa cells, L929 cells showed lower cell viability, more strongly response to oxidative stress and higher percentage in the G2/M phase of cell cycle. The appearance of sub-G1 peak, double staining with Annexin V-FITC/PI and the increase of Caspase-3 activity further confirmed apoptosis should be the major form of cell death. Moreover, the apoptotic pathway was clarified as follows. Firstly, reactive oxygen species (ROS) is generated induced by MnO@SiO2 NPs, then p53 is activated followed by an increase in the bax and a decrease in the bcl-2, ultimately leading to G2/M phase arrest, increasing the activity of caspase-3 and inducing apoptosis.


Sonohysterography: a valuable tool in evaluating the female pelvis.
A number of medical conditions, including abnormal uterine bleeding, endometrial cancer, monitoring tamoxifen therapy, infertility, and recurrent abortion, warrant investigation of the female genital tract. Diagnostic studies including hysterosalpingogram, ultrasound, and sonohysterography have proved useful in the investigation of these gynecologic conditions. This article discusses each of these tests with particular emphasis on sonohysterography and their current and potential contributions in both diagnostic and therapeutic applications. The utility of each as well as their comparative value to each other and existing gold standards is reviewed. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to outline the current screening methods for uterine cavity and pelvic abnormalities, to list the advantages of sonohysterography, and to describe the clinical situations where sonohysterography can be used.


[Post-embolic chronic pulmonary heart disease: a case report].
Echocardiography and pulmonary scintigraphy demonstrated post-embolic chronic cor pulmonale in a six-year-old woman presenting with dyspnoea. The patient's symptoms deteriorated during subsequent thromboembolic episodes, despite treatment consisting of oral anticoagulants and diuretics. After discussing the pathophysiology and diagnostic methods, the authors emphasize the limits of medical treatment of post-embolic chronic cor pulmonale and the value of two surgical treatments: thromboendarterectomy and lung transplantation. They also recall the precise selection criteria for lung transplantation.


Relationship between severity of reflux esophagitis according to the Los Angeles classification and esophageal motility.
We investigated the relationship between the severity of reflux esophagitis (RE) according to the Los Angeles (LA) classification and esophageal motility. We examined 28 healthy subjects (HS) and 48 RE patients (grade A of the LA classification, 16 patients; grade B, 16 patients; grade C or D, 16 patients). Esophageal manometry was performed by the intraluminal microtransducer method. Resting lower esophageal sphincter (LES) pressure was assessed by the rapid pull-through method. Esophageal contraction after ten repeated 5-ml water swallowings separated by 30-s intervals was measured at 3, 8, 13, and 18 cm above the LES. The resting LES pressure and the amplitude of esophageal contraction 3 cm above the LES in the grades C + D group were significantly lower than those in the HS group. The amplitude of esophageal contraction 3 cm above the LES in the grade B group was significantly lower than those in the grade A group and the HS group. The frequency of failed peristalsis in the grades C + D group was significantly higher than that in the HS group and the grade A and grade B groups. The present findings suggested that the severity of RE according to the LA classification would be likely to mainly reflect esophageal volume clearance.


Alternative care. Patient choices for adjunct therapies within a cancer center.
Prompted by an increased interest in and awareness of alternative medicine, the Sutter Cancer Center in Sacramento, California, sponsored a telephone survey of its cancer patients. The primary purpose of this 1994 survey was: 1) to determine patient perceptions and attitudes regarding alternative care providers, and 2) to determine whether the Sutter Cancer Center should provide support for these types of therapies to its patients. The Center conducted a 95-item telephone survey of its patients with cancer, using an independent professional research firm. A random sample of 503 adult patients completed the 15-minute telephone survey between January 27 and March 8, 1994. The sample included more women than men (62%, 38%, respectively), and patients ranged in age from 18 to 88 years. All respondents had been treated for cancer at the Center within the past 2 years. Survey questions included areas such as cancer diagnosis, awareness of alternative therapies, attitude toward alternative therapies, and perception of oncologists' attitude toward alternative therapies. The analysis of the survey results contained two phases: descriptive analysis and comparative analysis. The descriptive aspect is included in this report. Of the 503 respondents, 82 (16%) had considered utilizing alternative therapy for cancer after a diagnosis was made. Most respondents were moderately familiar with alternative therapy, such as nutrition therapy (59%), herbal therapy (63%), and acupuncture (62%). Only 6% of respondents actually saw a provider of alternative therapies; providers were most frequently nutritionists, counselors, herbalists, and massage therapists. The user patient profile clearly indicates that usage is highest in patients with a diagnosis of at least 1 year. Seventy-five percent reported that they would prefer to receive a referral from their doctors, while 20% would prefer to use a telephone referral line. Two thirds of patients felt that alternative care providers should be encouraged by the medical profession, and 85% indicated that alternative care should be offered at the cancer center as part of oncology treatment. The results of this survey clearly reflect the patients' desires to integrate mainstream medicine with some forms of alternative/complementary medicine. Consequently, the Sutter Cancer Center has established a multidisciplinary group of healthcare professionals, including oncologists, nurses, social workers, and alternative practitioners, to evaluate the clinical, psychosocial, and financial impact of integrating wellness/complementary medicine into the existing treatment model at this facility. Providing alternative therapy within a cancer center ensures the availability of both the most advanced conventional treatment and care as well as accurate information and guidance with regard to alternative therapies. This service allows the patient and the cancer care team to focus not only on the patient's physical symptoms, but also on his or her overall quality of life.


Anti-tumour imidazotetrazines. Part XXI. Mitozolomide and temozolomide: probes for the major groove of DNA.
The structural and electronic properties of the major groove-binding anti-tumour imidazotetrazinones, mitozolomide and temozolomide were studied using molecular orbital techniques. Structure-activity relationships of mitozolomide derivatives emphasized the importance of a hydrogen bond donor on the C8-substituent and showed that good activity would be expected for derivatives carrying a small C8-substituent with restricted negative potential. The coplanarity of the carboxamide substituent in mitozolomide is unlikely to be disrupted by hydrogen bonding in the major groove. Semi-empirical M.O. calculations gave a very high partial positive charge on C4, indicating an enhanced susceptibility to nucleophilic attack leading to ring opening at this position and the formation of a triazene alkylating agent.


The timing of fusion surgery for clival chordoma with occipito-cervical joint instability: before or after tumor resection?
Clival chordoma with occipito-cervical (OC) joint invasion can result in preoperative and postoperative instability. The authors investigate the appropriate timing of OC fusion to prevent instability-, fusion-, and surgery time-related morbidity. Twenty-two consecutive patients underwent surgery for clival chordoma from December 2008 to September 2014. OC fusion was performed for patients with OC joint invasion and instability due to preoperative destruction of the occipital condyle or extensive postoperative condylectomy. The data in relation to OC joint instability, fusion, and surgery time were analyzed retrospectively and compared between OC fusion before and after tumor resection. Of the 22 patients, 8 with tumor invasion of the OC joint underwent OC fusion. OC fusion was performed after tumor resection in one-stage for four patients and before tumor resection in two-stage for four patients. There was OC joint instability from tumor destruction of the occipital condyle in seven patients (87.5%). Patients with OC fusion after tumor resection encountered complications such as surgery site wound dehiscence, encephalitis, and cardiac arrest with consequent mortality in one patient. These complications were avoided in subsequent patients where OC fusion was performed before tumor resection. There were no differences in the extent of tumor resection between OC fusion before and after tumor resection. Two-stage OC fusion before tumor resection can reduce instability-, fusion-, and surgery time-related morbidity and achieve feasible tumor resection when OC joint instability is expected. The extent of tumor invasion and brain stem compression should be considered when fusion precedes tumor resection.


Medication errors in home care: a qualitative focus group study.
To explore registered nurses' experiences of medication errors and patient safety in home care. The focus of care for older patients has shifted from institutional care towards a model of home care. Medication errors are common in this situation and can result in patient morbidity and mortality. An exploratory qualitative design with focus group interviews was used. Four focus group interviews were conducted with 20 registered nurses in home care. The data were analysed using content analysis. Five categories were identified as follows: lack of information, lack of competence, reporting medication errors, trade name products vs. generic name products, and improving routines. Medication errors occur frequently in home care and can threaten the safety of patients. Insufficient exchange of information and poor communication between the specialist and home-care health services, and between general practitioners and healthcare workers can lead to medication errors. A lack of competence in healthcare workers can also lead to medication errors. To prevent these, it is important that there should be up-to-date information and communication between healthcare workers during the transfer of patients from specialist to home care. Ensuring competence among healthcare workers with regard to medication is also important. In addition, there should be openness and accurate reporting of medication errors, as well as in setting routines for the preparation, alteration and administration of medicines. To prevent medication errors in home care, up-to-date information and communication between healthcare workers is important when patients are transferred from specialist to home care. It is also important to ensure adequate competence with regard to medication, and that there should be openness when medication errors occur, as well as in setting routines for the preparation, alteration and administration of medications.


Effects of a competency-based counseling training program for correctional officers.
The purposes of this study were (a) to determine whether a competency-based counseling training program can be effective in developing the counseling skills of correctional officers with diverse backgrounds and (b) to examine if participants would demonstrate positive changes in counseling skills regardless of their differences among a variety of demographic variables. One hundred and six correctional officers were selected to participate in this study. Both qualitative and quantitative research methods were applied for collecting and analyzing data. The results indicate that the participants' counseling skills were significantly improved. Because the participants demonstrated positive changes in their overall counseling skills, the present research further supports no significant difference among a variety of variables. The training program also brought out deeper reflection on the significant learning experiences, greater theoretical knowledge, as well as greater understanding of the counseling work for the participants.


Studies on the corpuscles of Stannius of Botia lohachata.
The corpuscles of Stannius of Botia lohachata are made up of numerous large lobules, each of which is bounded by a septum and contains two types of cells. The secretory granules are PAS- and AF-positive, indicating that 1,2 glycol groups and non-sulphated mucoid substances are present. Detached cells in the lobule lumen are suggestive of holocrine secretion. The possibility of the existence of more than one secretory product is discussed.


[Acute fatty liver of pregnancy--case report].
Severe liver function disorders in late pregnancy are relatively rare but extremely dangerous, as they may quickly develop into a fulminant disease and become a life-threatening disorder for the mother and the fetus. In the following study we have reported a case of a previously healthy woman with severe liver disorder in the third trimester of pregnancy. On the basis of anamnesis, differential diagnosis, typical course and complications of the disease, and proper response to intensive supportive medical therapy, we diagnosed an acute fatty liver of pregnancy. The diagnosis was based on clinical presentation and laboratory abnormalities. Owing to timely intervention and adequate supportive care management, this severe complication of a pregnancy has had a successful outcome for both the mother and the child.


Average but not continuous speed match between motoneurons and muscle units of rat tibialis anterior.
1. Properties of single motoneuron/muscle-unit combinations were determined for tibialis anterior (TA) in rats anesthetized with pentobarbital. The TA observations were systematically compared with those obtained earlier by the use of the same techniques from rat medial gastrocnemius (MG). 2. TA motoneurons were investigated with regard to afterhyperpolarization (AHP; total duration 32-74 ms, amplitude 0.39-4.96 mV) and axonal conduction velocity (41-79 m/s). TA muscle-unit measurements included the time course of the isometric twitch (time-to-peak force 10.8-18.0 ms; total duration 42-92 ms), the maximum tetanic force (22-217 mN), and a measure of fatigue sensitivity (fatigue index 5-100%). The range of twitch and AHP durations ("speed range") was markedly smaller in the present TA material than for MG. 3. The mean duration of the TA motoneuronal AHP (49 +/- 8 ms, mean +/- SD) was close to that of its muscle-unit twitch (56 +/- 12 ms). Thus an "average" speed match existed between TA motoneurons and their muscle fibers. 4. For TA there was no correlation between the time courses of AHP and twitch. Thus there was for TA no "continuous" speed match between the motoneurons and their muscle fibers. 5. For TA twitches or AHPs studied separately, there was a significant correlation between different time course measures. Furthermore, compared with TA units having relatively fast twitches, those with slower twitches tended to show 1) a smaller maximum tetanic force and 2) a greater AHP amplitude. Fatigue-resistant units tended to have slower twitches than fatigue-sensitive ones.(ABSTRACT TRUNCATED AT 250 WORDS)


Vesiculopustular eruption in a neonate with trisomy 21 syndrome as a clue of transient myeloproliferative disorders.
We report the case of a vesiculopustular eruption associated with a transient myeloproliferative disorder (TMD) in a neonate with trisomy 21 syndrome. Examination of a skin biopsy showed a dermal mixed inflammatory infiltrate including atypical megakaryoblasts. As the white blood cell count spontaneously normalized, the eruption disappeared. This case report and review of the literature demonstrates that a vesiculopustular eruption could be an important clue to identify TMD in a neonate.


Inhibitors and enablers of physical activity in multiethnic hypertensive patients: qualitative study.
Regular physical activity (PA) can reduce blood pressure, but hypertensive patients in ethnic minority populations are often inactive. The objective of this qualitative study was to explore inhibitors and enablers of PA from the perspective of hypertensive Ghanaian, African-Surinamese and White-Dutch patients in Amsterdam, The Netherlands. In-depth individual interviews with 46 patients were analysed for thematic content, using Maxqda software. All three groups mentioned their hypertension, the presence of other health conditions, lack of priority, lack of social support, limited financial resources or access to PA facilities as inhibitors for maintaining or increasing their level of PA. Common enablers included health-related incentives, support from physicians or family and having physically demanding work. Specific inhibitors only mentioned by Ghanaians and Surinamese included inexperience with recommended 'Western' activities (cycling), little access to their habitual forms of PA, cultural preferences for large body sizes, unfamiliarity with the host country and the pressure of social demands from the Dutch society and their own communities. Specific enablers for Ghanaians and Surinamese included access to community or church-based support groups. These patient-identified inhibitors and enablers can be a useful framework for promoting PA in hypertensive patients, particularly from immigrant groups. Physicians may build their advice on the identified enablers and tackle the inhibitors.


Laparoscopic transgastric pancreatic pseudocystogastrostomy--first experience with extraluminal approach.
Transgastric cystogastrostomy (Jurasz procedure) became a standard procedure in the treatment of mature pancreatic pseudocysts contacting the stomach. The first experience with laparoscopically performed transgastric cystogastrostomy under performing anterior gastrostomy is discussed. Five ports were used. The anterior stomach wall was opened 2 cm in length. The communication channel with the pseudocyst was created by means of precise coagulation of the posterior stomach as well as the pseudocyst wall. The pseudocyst was evacuated and the stoma was completed by stapling with the EndoGIA lineal stapler 3 cm in length. The anterior stomach wall was also closed with EndoGIA stapler. Excellent results could be achieved. The pseudocyst resoluted within 1 month after the operation, and the anastomosis healed completely. The patient was discharged on the 8th post-operative day. The follow-up for 1 year was free of complications. Laparoscopic pseudocystogastrostomy appears to be a reliable method for treatment of large size mature pancreas pseudocysts because it is a minimally invasive procedure with standardized stapler-performed anastomosis. However, this initial experience has to be confirmed with a large number of patients.


Primary health care in the tropics.
Primary health care (PHC) organization as part of the country's health care system or of a community development system is compared and causes of failure of PHC programmes analyzed. PHC approach has too often forgotten the need for a well-designed suprastructure and/or that the perception in the communities of diseases and health care is strongly dependent on several attitude towards Western medicine. To avoid these blinkers, a good collaboration between health professionals, social scientists and indigenous people is very important during the planning process of PHC programmes.


A case control study to explore the risk factors for acquisition of leptospirosis in Surat city, after flood.
Between August and November 2006, a population-based case control study was conducted to identify the probable risk factors for leptospirosis during flooding in Surat city. Sixty-two laboratory confirmed cases out of 129 suspected cases, and 253 age and sex matched fever and healthy controls were interviewed with the help of predesigned questionnaire. The association of risk factors with acquiring leptospirosis was assessed by adjusted OR with the help of logistic regression model to control confounders. By univariate analysis, factors identified were, walking barefoot (OR = 10.34, 95% CI 5.09-21.31, P <0.05). Prompt and vigilant fever surveillance activities in pre-monsoon preparedness plan, intensive IEC messages, rodent control programs and improvement of environmental sanitary conditions may help to greatly reduce the incidence of leptospirosis.


Ceramide attenuates high glucose-induced cardiac contractile abnormalities in cultured adult rat ventricular myocytes.
Ceramide, the metabolic product of signaling molecule sphingomyelin, has been implicated in cardiac Ca2+ regulation. To study the possible role of ceramide in the pathogenesis of diabetic cardiomyopathy, we examined the effects of ceramide on the cardiac contractility of cultured ventricular myocytes under control and simulated diabetic environments. Adult rat ventricular myocytes were maintained in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium for 24 hr in the absence or presence of the membrane-permeant ceramide analog C2-ceramide, ceramide glucosyltransferase inhibitor D,L-threo-1-pheny-2-decanoylamino-3-morpholino-1-propanol (PDMP), or the inactive ceramide analog C2-dihydroceramide. Contractile indices analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (+/- dL/dt), and intracellular Ca2+ fura-2 fluorescence intensity (FFI). Myocytes maintained in HG medium displayed reduced PS and +/- dL/dt associated with prolonged TR90 and normal TPS compared to NG myocytes. Interestingly, the HG-induced mechanical dysfunctions were significantly attenuated by C2-ceramide or PDMP. C2-ceramide did not affect the myocyte mechanics in NG myocytes although PDMP shortened TPS without affecting any other indices. The HG-induced contractile abnormalities were not altered by inactive ceramide analog C2-dihydroceramide (except +/- dL/dt). Fura-2 fluorescence recording revealed that HG reduced baseline as well as stimulated intracellular Ca2+ levels, which may be abolished by both C2-ceramide and PDMP. These data suggest that alteration of ceramide signaling may play a role in the pathogenesis of diabetic cardiomyopathy.


Hydraulic fractionation of conventional water quality constituents in municipal dry- and wet-weather flow samples.
The effective design of treatment processes for combined sewer overflows (CSOs) requires understanding of the CSO characteristics and treatability. Environment Canada partnered with four municipalities to evaluate water quality and treatability of wet- and dry-weather flows at local sewage or CSO treatment facilities. Chemical characterization of the samples indicates that the municipal sewage at all of the sites is of relatively weak strength, with several differences between the water quality data for dry-weather and wet-weather flows (assumed to represent CSOs). Hydraulic separation of constituents with an elutriation apparatus illustrated the removals that can be expected with conventional settling techniques and differences in settling of various constituents.


Ultraviolet-B irradiation of leukapheresis. Products: dose-response relationship with the mixed lymphocyte reaction.
Ultraviolet-B (UVB) irradiation of blood constituents intensifies their anti-rejection effect in pretransplant donor-specific transfusions. UVB-induced inhibition of the mixed lymphocyte reaction (MLR) between UVB-irradiated donor cells and prospective recipient cells is a predicator of this anti-rejection effect. In order to define the dose-response relationship between the incident UVB irradiation on leukocyte concentrates and subsequent inhibition of their MLR responses, we collected 4 +/- 2 x 10(9) leukocytes (93 +/- 7% lymphocytes) in 200 ml plasma from each of three volunteers by leukapheresis and exposed them to rapid, serial doses of UVB irradiation which was delivered by a blood product irradiator (4R4440 UVB Irradiator, Baxter, Inc) with aliquots removed between doses. Lymphocytes from each aliquot were placed in MLR with panel donors and studied in three groups: 1) the panel donor cells were gamma-irradiated (1,500 rads) (i.e., only the UVB-irradiated cells could proliferate), 2) the UVB-irradiated cells were gamma-irradiated (i.e., only the panel lymphocytes could proliferate), and 3) no gamma-irradiation (i.e., both cell populations could proliferate). Each group had a similar UVB dose-related diminution in the MLR (p = .79, ANOVA). A single dose of 6 J/cm2 extinguished the MLR to baseline in all groups. This dose should theoretically prevent transfused cells from producing either graft-versus-host disease or allosensitization, and might heighten their tolerogenic effect. This dose will be employed in our study of donor-specific leukocyte transfusion in clinical renal transplantation.


[2 cases of encephalitis in immunodepressed patients].
The authors report two new cases of encephalitis occurring in association with immunity deficiency. The first concerns a child suffering from Bruton type congenital hypogammaglobulinemia. Histological examination of the brain under light microscopy shows important lesions of panencephalitis with parenchymal atrophy : the latter was more marked in the cerebellar lamellae. Ultra-structural examination showed numerous nuclear bodies in the nuclei of the macroglial cells and tubular inclusions situated in the cytoplasm of the capillary endothelial cells. The second case is that of a man of 44 years of age who had undergone a kidney transplant for malignant arterial hypertension, who after 3 months immunodepressive treatment suffered from temporo-spatial confusion together with a pyramidal tract syndrome. He died after 3 weeks evolution of the disease. Microscopical examination of the encephalon showed the presence of microglial nodules with aspects of neurophagia, suggestive of a polioencephalitis. These lesions were situated in the temporal cortex and the brain stem. The lymphocytic reaction was very slight in the second case.


Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens: A Randomized Trial Comparing Two Fixatives.
It is widely reported that neoadjuvant chemoradiation reduces lymph node yield in rectal cancer specimens. Some have questioned the adequacy of finding ≥12 lymph nodes for accurate staging, and fewer nodes were correlated with good response. Others reported that low lymph node count raises the chance for understaging and correlates with worse survival. In addition, a few studies demonstrated that diligent specimen analysis increases lymph node count. The aim of this study was to compare Carnoy's solution and formalin concerning lymph node yield in specimens of patients with rectal cancer after neoadjuvant chemoradiation. This is a prospective randomized trial that was conducted from 2012 to 2015. This study was performed in a reference cancer center in Brazil. Patients who underwent low anterior resection with total mesorectal excision after neoadjuvant chemoradiation for rectal adenocarcinoma were included. Rectosigmoid specimens were randomized for fixation with Carnoy's solution or formalin. A total of 130 specimens were randomized. After dissection, the residual fat from the formalin group was immersed in Carnoy's solution in search for missed lymph nodes (Revision). The Carnoy's solution group had superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases (mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients. Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph node count. This was a unicentric study. Compared with formalin, the Carnoy's solution increases lymph node count and reduces the cases with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis and this is clinically relevant. Finding <12 lymph nodes is not a sign of good response to neoadjuvant chemoradiation (www.clinicaltrials.gov. Unique identifier: NCT02629315). See Video Abstract at http://links.lww.com/DCR/A694.


Summer torpor in African woodland dormice Graphiurus murinus (Myoxidae:Graphiurinae).
We determined the effect of food availability (presence/absence) and ambient temperature (25/10 degrees C) on daily energy expenditure and the use of activity and torpor in summer-acclimated captive Graphiurus murinus. Daily energy expenditure declined logarithmically with duration of food deprivation at a mean rate of 11 and 31% per day at 25 and 10 degrees C, respectively. The incidence of torpor in the presence of food at 25 degrees C was low (one in seven individuals) and increased on a single day's exposure to 10 degrees C and with duration of food deprivation. Use of torpor was highest during the day, varied between individuals, and torpor bouts of greater than 24 h duration were not noted. With food deprivation, individuals at 25 degrees C initially responded by reducing activity but remained euthermic while the same individuals at 10 degrees C responded by increasing their use of torpor during the light period: this difference in response probably reflects a difference in the relative energetic benefits of torpor at different temperatures.


Effect of multiple sclerosis alpha 2-macroglobulin on mitogen induction of lymphocyte proliferation.
Electrophoretic studies on microheterogeneity of alpha 2-macroglobulin (alpha 2M) have revealed the presence of an abnormal acidic form of alpha 2M in multiple sclerosis (MS). In the present study we have characterized alpha 2M chemically and compared the inhibitory effect of MS and normal alpha 2M on the mitogen induction of lymphocyte proliferation. The antitrypsin activity and total reducing sugar content of MS alpha 2M were comparable with those of normal alpha 2M. However, the sialic acid content of MS alpha 2M was found to be significantly higher than that of normal alpha 2M. In agreement with previous studies, normal alpha 2M was found to inhibit the mitogen induction of lymphocyte proliferation in more than 90% cell cultures. However, MS alpha 2M was found to inhibit the mitogen-induced lymphocyte proliferation in less than 35 percent cell cultures. The effects of MS or normal alpha 2M on the lymphocyte cultures of either groups were found to be apparently the same. The possible explanations for the loss of the above-mentioned inhibitory effect of MS alpha 2M have been discussed.


Pharmacological and Genetic Manipulation of p53 in Brown Fat at Adult But Not Embryonic Stages Regulates Thermogenesis and Body Weight in Male Mice.
p53 is a well-known tumor suppressor that plays multiple biological roles, including the capacity to modulate metabolism at different levels. However, its metabolic role in brown adipose tissue (BAT) remains largely unknown. Herein we sought to investigate the physiological role of endogenous p53 in BAT and its implication on BAT thermogenic activity and energy balance. To this end, we generated and characterized global p53-null mice and mice lacking p53 specifically in BAT. Additionally we performed gain-and-loss-of-function experiments in the BAT of adult mice using virogenetic and pharmacological approaches. BAT was collected and analyzed by immunohistochemistry, thermography, real-time PCR, and Western blot. p53-deficient mice were resistant to diet-induced obesity due to increased energy expenditure and BAT activity. However, the deletion of p53 in BAT using a Myf5-Cre driven p53 knockout did not show any changes in body weight or the expression of thermogenic markers. The acute inhibition of p53 in the BAT of adult mice slightly increased body weight and inhibited BAT thermogenesis, whereas its overexpression in the BAT of diet-induced obese mice reduced body weight and increased thermogenesis. On the other hand, pharmacological activation of p53 improves body weight gain due to increased BAT thermogenesis by sympathetic nervous system in obese adult wild-type mice but not in p53(-/-) animals. These results reveal that p53 regulates BAT metabolism by coordinating body weight and thermogenesis, but these metabolic actions are tissue specific and also dependent on the developmental stage.


A functional magnetic resonance imaging study of the neuronal specificity of an acupoint: acupuncture at Rangu (KI 2) and its sham point.
The neuronal specificity of acupoints has not been entirely supported by the results of previous functional magnetic resource imaging studies. This study tested the specificity of an acupoint using right Rangu (KI 2) and its sham acupoint. The results showed specific cerebral response patterns and thus provided the evidence of the existence of acupoint neuronal specificity.


[Fusion of protoplasts of inactive variants of 2 producers of actinomycin C and the biosynthesis of an antibiotic of non- actinomycin nature].
Fusion of protoplasts of double auxotrophic mutants of spontaneous inactive variants of two cultures producing actinomycin C, i.e. Streptomyces chrysomalus 305 and Streptomyces sp. 26-115 induced by PEG-600 yielded a number of stable recombinants. One of the recombinants requiring proline for its growth was designated as recPro. Unlike its parent strains, it synthesized an antibiotic substance active against gram-positive bacteria and Saccharomyces cerevisiae. The nature of the substance is under investigation.


Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis.
Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.


Changing land use and its impact on the habitat suitability for wintering Anseriformes in China's Poyang Lake region.
As an internationally important wetland for migratory waterbirds, China's Poyang Lake region has experienced substantial changes in land use during the past two decades owing to climate change and anthropogenic disturbances. Recent dam constructions on the Yangtze River and its tributaries for agriculture and hydroelectric power exert strong effects on the hydrological regimes of this lake. However, few studies have investigated how the land-use changes through time affect the habitat suitability for wintering Anseriformes-the largest community in this region. Thus, it is necessary to timely monitor changes in the habitat quality and understand the potential factors that alter it. In this study, three periods (1995, 2005 and 2014) of typical environmental indicators that have direct impacts on foraging and resting for the Anserformes, including proximity to water (density of lakes, rivers and ponds), human disturbances (density of residences and various road networks), preferred land cover types and food availability (NDVI), are integrated to develop a habitat suitability index model for habitat mapping. The results indicate that long-term lake shrinkage in low-water periods led to greatly expanded wetlands in these years, which provided more suitable habitat for migratory waterfowl. The amount of highly suitable habitat in 2014 was nearly twice as much as in 1995. Recent survey data from 1997 to 2013 also revealed an increase in the population size, and confirmed the improvement of habitat suitability in the Poyang Lake region. Spatial analysis revealed that land use changes contributed most to the improved habitat coverage between 1995 and 2014. However, the relative significances of these transformations for highly suitable and moderately suitable habitats are strikingly different. Increases in wetland and paddy field area are the main reasons for explaining these improvements, respectively. The framework model proposed in this study will help governments to evaluate habitat conservation and restoration for protecting waterbirds in a spatially explicit way.


A new method for PET image reconstruction using Fourier-Wavelet moment.
In this paper, a new non-regularization method for positron emission tomography (PET) reconstruction is proposed. The proposed method is a feature-based method using Fourier-Wavelet basis. In order to obtain the reconstructions, we have to calculate the Fourier-Wavelet moment (FWM) from the measurements. To achieve this, iterative method is employed. The rotation invariance property of the proposed basis permits us to reduce computational cost. A row-action (RA) like fast convergent algorithm is used to further accelerate the convergence rate. In experiment, we compare the proposed method with some existing algorithms. The results show that our method offers good reconstruction quality compared to conventional MAP method.


Maternal lead exposure and the secondary sex ratio.
A reduction in the secondary sex ratio may be associated with exposure to environmental toxicants. Little data exists relating this outcome to lead exposure, a well-known reproductive toxicant. We studied 1980 women having singleton births from 1994 to 1995 and from 1997 to 2001 who participated in a cohort study of lead exposure and infant outcomes in Mexico City. Levels of lead were measured in maternal and cord blood using graphite furnace atomic absorption spectroscopy, and levels of lead in maternal patella and tibia bone (a reflection of cumulative exposure) were measured using noninvasive K-X-ray fluorescence measurements. Using logistic regression models, we evaluated the relations of these measures to secondary sex ratio in the offspring, adjusting for maternal age, parity and year of infants' birth. We found no consistent association between any of the lead measures and secondary sex ratio. Results were unchanged when we adjusted for infants' year of birth, maternal age and parity. Despite a large sample size and the use of sensitive biomarkers, we did not find evidence that maternal and fetal lead exposure is associated with a lower secondary sex ratio among newborns.


Performance characteristics of a novel reusable intermediate-volume low-pressure cuffed endotracheal tube.
To evaluate the performance of the reusable intermediate-volume low-pressure cuffed "Super Safety Yellow" (Willy Rüsch AG, P.O. Box 1620, D-71332 Waiblingen, Germany) endotracheal tube with regard to cuff seal, tube tip position, and incidence of postoperative throat complaints. The "Super Safety Yellow" was compared with the "Super Safety Clear" (W. Rüsch AG), the "lo-pro (Mallinckrodt Laboratories, Cornamady, Athlone County, Ireland), and the "red rubber" (W. Rüsch AG) tubes. Two hundred adult patients scheduled for minor surgery under standardized general anaesthesia were allocated to one of these tubes. Past-cuff leakage (indicator; orally instilled 0.2% indigocarmine) as well as intratracheal tube tip position (degree of being centred) were assessed by fibre-optic tracheoscopy. The semi-standardized interviews for the recording of postoperative sore throat were performed in double-blind fashion once a day, starting on the day of operation till p.o. day 3. chi 2-test; significance: P < 0.05. A past-cuff leakage was found in three "red rubber" tubes. There were significant differences in tube tip position with the "Super Safety Clear" being best, and the "Super Safety Yellow" being worst centred (P = 0.010). The incidence of postoperative throat complaints showed a nonsignificant tendency in favour of the PVC-tubes. A significant number of such complaints were observed in women (P = 0.0004) and in obese patients (P = 0.011). By contrast, this incidence did not significantly differ with age, tracheal cross-sectional shape, tube tip position, use of atropine, and duration of intubation. Although resembling the "red rubber" tube in the incidence of postoperative throat complaints, the "Super Safety Yellow" may be an alternative to the currently used disposable tubes in anaesthesia. Its performance is comparable with regard to cuff seal and intra-cuff pressure. Additionally, it helps in reducing PVC waste and may lessen costs.


Realistic spin glasses below eight dimensions: A highly disordered view.
By connecting realistic spin glass models at low temperature to the highly disordered model at zero temperature, we argue that ordinary Edwards-Anderson spin glasses below eight dimensions have at most a single pair of physically relevant pure states at nonzero low temperature. Less likely scenarios that evade this conclusion are also discussed.


Duplicate sfrp1 genes in zebrafish: sfrp1a is dynamically expressed in the developing central nervous system, gut and lateral line.
The secreted frizzled-related proteins (Sfrp) are a family of soluble proteins with diverse biological functions having the capacity to bind Wnt ligands, to modulate Wnt signalling, and to signal directly via the Wnt receptor, Frizzled. In an enhancer trap screen for embryonic expression in zebrafish we identified an sfrp1 gene. Previous studies suggest an important role for sfrp1 in eye development, however, no data have been reported using the zebrafish model. In this paper, we describe duplicate sfrp1 genes in zebrafish and present a detailed analysis of the expression profile of both genes. Whole mount in situ hybridisation analyses of sfrp1a during embryonic and larval development revealed a dynamic expression profile, including: the central nervous system, where sfrp1a was regionally expressed throughout the brain and developing eye; the posterior gut, from the time of endodermal cell condensation; the lateral line, where sfrp1a was expressed in the migrating primordia and interneuromast cells that give rise to the sensory organs. Other sites included the blastoderm, segmenting mesoderm, olfactory placode, developing ear, pronephros and fin-bud. We have also analysed sfrp1b expression during embryonic development. Surprisingly this gene exhibited a divergent expression profile being limited to the yolk syncytium under the elongating tail-bud, which later covered the distal yolk extension, and transiently in the tail-bud mesenchyme. Overall, our studies provide a basis for future analyses of these developmentally important factors using the zebrafish model.


High-intensity interval training increases intrinsic rates of mitochondrial fatty acid oxidation in rat red and white skeletal muscle.
High-intensity interval training (HIIT) can increase mitochondrial volume in skeletal muscle. However, it is unclear whether HIIT alters the intrinsic capacity of mitochondrial fatty acid oxidation, or whether such changes are associated with changes in mitochondrial FAT/CD36, a regulator of fatty acid oxidation, or with reciprocal changes in the nuclear receptor coactivator (peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α)) and the corepressor (receptor-interacting protein 140 (RIP140)). We examined whether HIIT alters fatty acid oxidation rates in the isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria of red and white skeletal muscle and (or) induces changes in muscle PGC-1α and RIP140 proteins and mitochondrial FAT/CD36 protein content. Rats were divided into untrained or HIIT-trained groups. HIIT animals performed 10 bouts of 1-min high-intensity treadmill running (30-55 m·min(-1)), separated by 2 min of rest, for 5 days a week for 4 weeks. As expected, after the training period, HIIT increased mitochondrial enzymes (citrate synthase, COXIV, and β-hydroxyacyl CoA dehydrogenase) in red and white muscle, indicating that muscle mitochondrial volume had increased. HIIT also increased the rates of palmitate oxidation in mitochondria of red (37% for SS and 19% for IMF) and white (36% for SS and 12% for IMF) muscle. No changes occurred in SS and IMF mitochondrial FAT/CD36 proteins, despite increasing FAT/CD36 at the whole-muscle level (27% for red and 22% for white). Concurrently, muscle PGC-1α protein was increased in red (22%) and white (16%) muscle, but RIP140 was not altered. These results indicate that increases in SS and IMF mitochondrial fatty acid oxidation induced by HIIT are accompanied by an increase in PGC-1α, but not RIP140 or FAT/CD36.


Modeling the protonation states of β-secretase binding pocket by molecular dynamics simulations and docking studies.
β-secretase (BACE1) is an aspartyl protease that processes the β-amyloid peptide in the human brain in patients with Alzheimer's disease. There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Although it is believed that the net charge of the Asp dyad is -1, the exact protonation state still remains a matter of debate. We carried out molecular dynamic (MD) simulations for the four protonation states of BACE1 proteins. We applied Glide docking studies to 21 BACE1 inhibitors against the MD extracted conformations. The dynamic results infer that the protein/ligand complex remains stable during the entire simulation course for HD32D228 model. The results show that the hydrogen bonds between the inhibitor and the Asp dyad are maintained in the 10,000th ps snapshot of HD32D228 model. Our results also reveal the significant loop residues in maintaining the active binding conformation in the HD32D228 model. Molecular docking results show that the HD32D228 model provided the best enrichment factor score, suggesting that this model was able to recognize the most active compounds. Our observations provide an evidence for the preference of the anionic state (HD32D228) in BACE1 binding site and are in accord with reported computational data. The protonation state study would provide significant information to assign the correct protonation state for structure-based drug design and docking studies targeting the BACE1 proteins as a tactic to develop potential AD inhibitors.


Contact angles of diiodomethane on silicon-doped diamond-like carbon coatings in electrolyte solutions.
The influence of surrounding electrolyte type and concentration on the contact angle of hydrophobic diiodomethane on silicon-doped diamond-like carbon (DLC) coatings was examined to provide insight into how the presence of electrolytes in the solution influences adhesion of hydrophobic material to doped DLC surfaces. There was a small but statistically significant increase of contact angle with increasing electrolyte concentration over the range from 0 to approximately 0.01 M, after which the contact angle was virtually unaffected by further increase in the concentration of electrolyte. It was shown that CaCl(2) has a stronger influence on the change of the contact angle than NaCl, and that an increase in Si content in the DLC coatings increased the change in the contact angle of diiodomethane for all types of electrolyte. These observations suggest that the adhesion to the Si-doped DLC surfaces is reduced by addition of the electrolytes to the surrounding solvent. This could be explained by increased ion adsorption on the DLC surface with increase in silicon doping, causing the surfaces to be more hydrophilic.


Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion.
Members of the NDRG (N-Myc downstream-regulated) gene family have been shown to play a variety of roles in human malignancies. Recently, it was shown decreased expression in clear cell renal cell carcinoma (CCRCC) and inhibited cell proliferation, but the role of the NDRG2 in CCRCC invasion has not been described. We examined the expression of NDRG2 protein in CCRCC samples and the association between NDRG2 expression and CCRCC patients survival. Real-time RT-PCR and immunohistochemical analysis were used to measure NDRG2 expression in 60 paired CCRCC and adjacent normal tissues. Changes in cell invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. We found that NDRG2 expression is significantly down-regulated in CCRCC at mRNA and protein levels in a manner negatively associated with aggressive tumor behaviors, such as TNM stage (P = 0.003), Fuhrman's grade (P = 0.024), tumor invasion (P = 0.001) and tumor recurrence (P = 0.004), as well as shorter patient survival rates (P = 0.0041). Furthermore, NDRG2 could suppress CCRCC cell invasion through regulating MMP-9 expression and activity. So, these results suggest that NDRG2 can inhibit extracellular matrix-based tumor cell invasion and thereby play important roles in suppressing tumor metastasis in CCRCC. NDRG2 expression may also be a significant prognostic indicator for CCRCC.


United States life tables, 2010.
Objectives-This report presents complete period life tables for the United States by race, Hispanic origin, and sex, based on agespecific death rates in 2010. Methods-Data used to prepare the 2010 life tables are 2010 final mortality statistics; April 1, 2010 population estimates based on the 2010 decennial census; and 2010 Medicare data for persons aged 66-99. The methodology used to estimate the 2010 life tables was first implemented with data year 2008. The methodology used to estimate the life tables for the Hispanic population remains unchanged from that developed for the publication of life tables by Hispanic origin for data year 2006. Results-In 2010, the overall expectation of life at birth was 78.7 years. Between 2009 and 2010, life expectancy at birth increased for all groups considered. Life expectancy increased for both males (from 76.0 to 76.2) and females (80.9 to 81.0) and for the white population (78.8 to 78.9), the black population (74.7 to 75.1), the Hispanic population (81.1 to 81.4), the non-Hispanic white population (78.7 to 78.8), and the non-Hispanic black population (74.4 to 74.7).