Appointing silver and bronze standards for noncovalent interactions: a comparison of spin-component-scaled (SCS), explicitly correlated (F12), and specialized wavefunction approaches.
A systematic examination of noncovalent interactions as modeled by wavefunction theory is presented in comparison to gold-standard quality benchmarks available for 345 interaction energies of 49 bimolecular complexes. Quantum chemical techniques examined include spin-component-scaling (SCS) variations on second-order perturbation theory (MP2) [SCS, SCS(N), SCS(MI)] and coupled cluster singles and doubles (CCSD) [SCS, SCS(MI)]; also, method combinations designed to improve dispersion contacts [DW-MP2, MP2C, MP2.5, DW-CCSD(T)-F12]; where available, explicitly correlated (F12) counterparts are also considered. Dunning basis sets augmented by diffuse functions are employed for all accessible ζ-levels; truncations of the diffuse space are also considered. After examination of both accuracy and performance for 394 model chemistries, SCS(MI)-MP2/cc-pVQZ can be recommended for general use, having good accuracy at low cost and no ill-effects such as imbalance between hydrogen-bonding and dispersion-dominated systems or non-parallelity across dissociation curves. Moreover, when benchmarking accuracy is desirable but gold-standard computations are unaffordable, this work recommends silver-standard [DW-CCSD(T**)-F12/aug-cc-pVDZ] and bronze-standard [MP2C-F12/aug-cc-pVDZ] model chemistries, which support accuracies of 0.05 and 0.16 kcal/mol and efficiencies of 97.3 and 5.5 h for adenine·thymine, respectively. Choice comparisons of wavefunction results with the best symmetry-adapted perturbation theory [T. M. Parker, L. A. Burns, R. M. Parrish, A. G. Ryno, and C. D. Sherrill, J. Chem. Phys. 140, 094106 (2014)] and density functional theory [L. A. Burns, Á. Vázquez-Mayagoitia, B. G. Sumpter, and C. D. Sherrill, J. Chem. Phys. 134, 084107 (2011)] methods previously studied for these databases are provided for readers' guidance.


A Small Push-Pull Fluorophore for Turn-on Fluorescence.
A new class of push-pull dyes is reported based on the structures of benzoxa- and benzothiadiazole heterocycles. This new class of dyes displays red-shifted wavelengths of emission and greater sensitivity to polarity and hydrogen bonding solvents relative to previously known derivatives.


Pharmacokinetics of mirtazapine and its main metabolites after single intravenous and oral administrations in rats at two dose rates.
Mirtazapine (MRZ) is a human antidepressant drug metabolized to 8-OH mirtazapine (8-OH) and dimethylmirtazapine (DMR) metabolites. Recently, this drug has been proposed as a potential analgesic for use in a multidrug analgesic regime in the context of veterinary medicine. The aim of this study was to assess the pharmacokinetics of MRZ and its metabolites DMR and 8-OH in rats. Eighteen fasted, healthy male rats were randomly divided into 3 groups (n = 6). Animals in these groups were respectively administered MRZ at 2 and 10 mg/kg orally and 2 mg/kg intravenously. Plasma MRZ and metabolite concentrations were evaluated by HPLC-FL detection method. After intravenous administration, MRZ was detected in all subjects, while DMR was only detected in three. 8-OH was not detected. After oral administration, MRZ was detected in 3 out of 6 rats treated with 2 mg/kg, it was detected in 6 out of 6 animals in the 10 mg/kg group. DMR was only detectable in the latter group, while 8-OH was not detected in either group. The oral bioavailability was about 7% in both groups. The plasma concentration of the MRZ metabolite 8-OH was undetectable, and the oral bioavailability of the parental drug was very low.


Acyclovir therapy in herpes zoster infection. A practical guide.
The effect of acyclovir on the skin rash and herpes zoster keratouveitis has been studied. It has been shown to have a significant effect on both disease processes, and to be superior to topical steroids in the treatment of herpes zoster keratouveitis. Steroids have been found to have an adverse effect with prolonged treatment and frequent recurrences.


How and why genetic linkage has not solved the problem of psychosis: review and hypothesis.
The author examined the chromosomal linkage method as an approach to the genetic basis of schizophrenia and bipolar disorder. Comparisons were conducted of recent meta-analyses of genome scans of schizophrenia and bipolar disorder and of the three largest (N>300) sibling pair studies of schizophrenia and schizoaffective disorder and a comparable study of bipolar illness. Recent meta-analyses have not identified consistent sites of linkage. The three largest studies of schizophrenia fail to agree on a single locus, no commonality with bipolar illness has been demonstrated, and there is no replicable support for any of the current candidate genes. An alternative to the concept that DNA sequence variation lies in "multiple genes of small effect" is the hypothesis that the variation is epigenetic but related to the genetic transition ("the speciation event") that separated Homo sapiens from a prior hominid species. This hypothesis draws attention to the chromosomal rearrangement (the Xq21.3/Yp translocation) that occurred some 6 million years ago in the hominid lineage and subsequent rearrangements, including a paracentric inversion, that have taken place within the translocated segment. Here it is argued that the most recent of these events is relevant to specifically human characteristics, including language. The gene pair protocadherin X and Y within this region is under new selective pressure and is in a novel (epigenetic) situation with respect to X inactivation. Epigenetic variation associated with chromosomal rearrangements that occurred in the hominid lineage and that relates to the evolution of language could account for predisposition to schizophrenia and schizoaffective and bipolar disorder and failure to detect such variation by standard linkage approaches.


Biopsy eosinophilia as a predictor of renal graft dysfunction.
The aim of this research was to assess the impact of eosinophilia in renal biopsy specimens obtained during an acute rejection (AR) episode on the severity and reversibility of rejection and on long-term graft function. Among 165 renal graft recipients who underwent transplantation (Tx) in 2001 and 2002 whose biopsy specimens revealed AR, 49 with tissue eosinophilia were compared with control group of 48 without this feature. The average biopsy time was 60.6 and 95.8 days, respectively. Biopsies during delayed graft function were performed in 46.9% of patients with eosinophilia and 29% in the control group. The immunosuppressive regimen was based on tacrolimus or cyclosporine. Tissue eosinophilia was observed in 49 of 165 patients (29.6%): 5 patients had eosinophilia <10/mm(2), 31 patients 10-100/mm(2), 13 patients >100mm(2) (3 patients >300/mm(2)). Severity of AR according to Banff score was statistically lower in the control group (P <.002). Patients with tissue eosinophilia who initially received steroid-free treatment presented with significantly higher (P =.02) biopsy/patients index (2.3 vs 1.81) than the total eosinophilic group. Serum creatinine values at 6 and 12 months after transplantation (Tx) were higher among eosinophilic when compared with the control group (2.41 vs 1.82 mg/dL, P <.002; 2.10 vs 1.98 mg/dL, P =.006, respectively). Chronic rejection within the first year occurred in 25% of patients with tissue eosinophilia, and 8.3% of patients in the control group. One-year graft survival rate among patients with tissue eosinophilia was lower compared with the control group (89.8% and 93.7%, respectively). Biopsy eosinophilia is a negative predictor that indicates a more severe course of AR and a worse response to treatment with the threat of chronic graft dysfunction.


[NF-kappaB expression in lung tissue of acute lung injury rat model and the influence by antioxidant N-acetylcysteine].
To observe the NF-kappaB expression in the lung tissue of LPS-induced acute lung injury(ALI) rat model and the influence of N-acetylcysteine (NAC) on NF-kappaB expression. The expression of NF-kappaB in lung tissue in ALI rat model and the influence of NAC on NF-kappaB expression were detected by immunohistochemical (ABC) staining and Western blot. There were a small amount of sporadic NF-kappaB cells in airway epithelium and interstitium in normal control group. In contrast, nuclear NF-kappaB expression-positive cells increased obviously in airway mucosa, lung interestium, alveolar cavity and vascular wall of ALI rats. NF-kappaB(+) cells were mainly airway mucosa epithelial cells, infiltrating inflammatory cells, alveolar epithelial cells, and vascular endothelial cells. The NF-kappaB expression-positive cells in NAC therapy group notably decreased compared with ALI group and control group(P<0.01). Western blot analysis showed that the expression of NF-kappaB was different at various time points, reaching the peak at 3 h and then decreased (P<0.01) after LPS induced lung injury. In LPS induced acute lung injury rat model, the NF-kappaB nuclear expression increased obviously in airway mucosa, lung interestium and alveolar cavity. Most cells in lung tissue participated in the activation of NF-kappaB. NAC could alleviate inflammation by inhibiting activation of NF-kappaB.


Effect of the long-term administration of Cyclosporine A on bone healing around osseointegrated titanium implants: A histomorphometric study in the rabbit tibia.
The aim of this study was to investigate the effect of cyclosporine A (CsA) therapy on bone healing around osseointegrated implants in the rabbit by means of descriptive histologic and histomorphometric analyses. Eighteen rabbits received one implant each in the right tibia proximal metaphysis. After the bone-healing period of 3 months, 6 randomly selected animals were sacrificed (Group CTL-12) before the immunosuppression therapy initiation to obtain a standard of implant integration. Another six randomly selected animals were submitted to a daily subcutaneous (sc) injection of 10 mg/kg CsA (Group CsA) whereas the six remaining animals received daily sc injections of saline solution (Group CTL-24). Groups CTL-24 and CsA were sacrificed after another 12 weeks. Bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) within the implant threads were measured. Bone density (BD) and descriptive histological analyses were also accomplished. Rabbits under CsA therapy presented statistically lower percentage of BIC (33.28 ± 6.19) compared to the animals of CLT-24 (55.6 ± 17.73). No differences were found between CsA and CTL-12 (38.7 ± 7.87). Significant decreased percentage of BAFO between the implant threads in the CsA (48.43 ± 9.48) group compared to the CTL-24 (72.26 ± 11.72) was observed. No differences were found between CsA and CTL-12 (61.99 ± 13.94) groups. BD analysis showed significant lower BD in the CsA (48.56 ± 9.32) group compared to the CTL-12 (68.74 ± 10.89) and CTL-24 (77.96 ± 4.96) groups. Collectively, our findings demonstrated that CsA therapy negatively affect the bone healing around osseointegrated implants due to the significant lower values for BIC, BAFO, and BD.


Deriving individualised /r/ targets from the acoustics of children's non-rhotic vowels.
In visual-acoustic biofeedback for rhotic errors, learners are guided to match the third formant (F3) location to a visual target on a real-time acoustic spectrum. As the acoustic properties of correct English /r/differ across speakers, this study aimed to improve target selection by investigating the validity of individualised targets derived from children's non-rhotic vowels. A previously proposed prediction formula was adjusted using data from a child normative sample and tested in two groups of children. Study 1 found that predicted values were unexpectedly higher than actual F3 values in children whose /r/ errors had been remediated. To understand this discrepancy, Study 2 applied the formula to typically developing children and found that predicted values were also higher than actual F3 values, suggesting that different normative data might better represent the current samples. An updated formula is proposed, which can be used to generate individualised targets within acoustic biofeedback applications.


Therapeutic efficacy of low-dose steroid combined with hyaluronidase in ultrasonography-guided intra-articular injections into the shoulder for adhesive capsulitis.
The purpose of this study was to compare the efficacy of low-dose steroid, highdose steroid, and low-dose steroid combined with hyaluronidase with respect to intra-articular injection therapy for adhesive capsulitis (AC) of the shoulder. Thirty patients with primary AC in the initial stage were randomly assigned into three groups to receive ultrasound-guided intra-articular injections with 20 mg of triamcinolone acetonide (group A, n=10), 40 mg of triamcinolone acetonide (group B, n=10) and 20 mg of triamcinolone acetonide combined with hyaluronidase (group C, n=10). The outcome measures included a visual analogue scale (VAS), the Shoulder Disability Questionnaire (SDQ), abduction and external rotation range of motion, and intra-sheath fluid (ISF) before treatment and at 2, 4, 8, and 16 weeks after treatment. Among the 30 patients, one participant in group B dropped out; therefore, a total of 29 patients completed this study and were successfully injected. After the injection, the VAS, SDQ, range of flexion and external rotation, and ISF improved in all groups compared with the preinjection status, regardless of treatment or time point. In the comparison between groups, the SDQ and ISF showed significantly greater improvements in groups B and C than in group A. The therapeutic efficacy of combined low-dose corticosteroid and hyaluronidase is superior to that of low-dose corticosteroid and equivalent to that of high-dose corticosteroid in early AC.


Localization of high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae by immunoelectron microscopy.
A family of high-molecular-weight (HMW) surface-exposed proteins important in the attachment of nontypeable Haemophilus influenzae (NTHi) to human epithelial cells was previously identified (J. W. St. Geme III, S. Falkow, and S. J. Barenkamp, Proc. Natl. Acad. Sci. USA 90:2875-2879, 1993). In the present investigation, indirect immunogold labeling and electron microscopy were used to localize these proteins on three clinical isolates of NTHi, mutants deficient in expression of one or both HMW proteins, and embedded sections of human oropharyngeal cells after incubation with NTHi strain 12. The filamentous material comprising the proteins was labeled with monoclonal antibodies directed against two prototype HMW proteins (HMW1 and HMW2) of prototype NTHi strain 12. Gold labeling was observed as a cap or discrete aggregate off one pole or centrally along one long axis of the bacterial cell. Heavily labeled, non-bacterial-cell-associated, disk-like aggregates of the HMW proteins were frequently noted in both bacterial preparations as well as in association with the oropharyngeal cell surface and intracellularly. Mutants demonstrated diminished labeling or an absence thereof, respectively, which correlated well with their previously demonstrated reduced ability or inability to adhere to Chang conjunctival epithelial cells in vitro. The Haemophilus HMW proteins share antigenic determinants with and demonstrate amino acid sequence similarity to the filamentous hemagglutinin protein of Bordetella pertussis, a critical adhesin of that organism. The studies presented here demonstrate that the Haemophilus proteins and B. pertussis filamentous hemagglutinin show impressive morphologic and perhaps additional functional similarity.


Comprehensive screening of low nitrogen tolerant maize based on multiple traits at the seedling stage.
Plants tolerant to low nitrogen are a quantitative trait affected by many factors, and the different parameters were used for stress-tolerant plant screening in different investigations. But there is no agreement on the use of these indicators. Therefore, a method that can integrate different parameters to evaluate stress tolerance is urgently needed. Six maize genotypes were subject to low nitrogen stress for twenty days. Then seventeen traits of the six maize genotypes related to nitrogen were investigated. Nitrogen tolerance coefficient (NTC) was calculated as low nitrogen traits to high nitrogen traits. Then principal component analysis was conducted based on the NTC. Based on fuzzy mathematics theory, a D value (decimal comprehensive evaluation value) was introduced to evaluate maize tolerant to low nitrogen. Three maize (SY998, GEMS42-I and GEMS42-II) with the higher D value have better growth and higher nitrogen accumulation under low nitrogen conditions. In contrast, Ji846 with the lowest D value has the lowest nitrogen accumulation and biomass in response to nitrogen limitation. These results indicated that the D value could help to screen low nitrogen tolerant maize, given that the D value was positively correlated with low nitrogen tolerance in maize seedlings. The present study introduced the D value to evaluate stress tolerance. The higher the D value, the greater tolerance of maize to low nitrogen stress. This method may reduce the complexity of the investigated traits and enhance the accuracy of stress-tolerant evaluation. In addition, this method not only can screen potentially tolerant germplasm for low-nitrogen tolerance quickly, but also can comprise the correlated traits as many as possible to avoid the one-sidedness of a single parameter.


Unreported vertebral body compression fractures at abdominal multidetector CT.
To retrospectively assess the prevalence and clinical outcomes of unreported vertebral compression fractures at abdominal computed tomography (CT). This HIPAA-compliant study had institutional review board approval; the need for informed consent was waived for this retrospective analysis. A total of 2041 consecutive adult patients (1640 women, 401 men; age range, 19-94 years) underwent both abdominal multidetector CT and dual-energy x-ray absorptiometry (DXA) within 6 months of each other between 2000 and 2007, before sagittal CT reconstructions were obtained routinely. Transverse (axial) and retrospective sagittal multidetector CT reconstructions were reviewed for the presence of moderate or severe vertebral body compression fractures of the lower thoracic and lumbar spine by using the Genant visual semiquantitative method. Twenty-six patients were excluded for evidence of pathologic fracture or for technical factors limiting compression fracture detection. Electronic medical records were reviewed for patients with moderate or severe compression fractures to determine whether the fracture was reported at prospective CT interpretation, was known previously, or was diagnosed subsequently. Correlation was made with central DXA T scores. Statistical analysis was performed with the Student t test and Fisher exact test. At least one moderate or severe vertebral body compression fracture was identified retrospectively at CT in 97 patients (mean age, 70.8 years). Fractures involved one level in 67 and multiple levels in 30 patients, for a total of 141 fractures. In 81 (84%) patients, prospective CT diagnosis was not made. Patients in whom fractures were reported prospectively were significantly older and were more likely to have a severe compression fracture (P < .05). In 52 (64%) patients with an unreported fracture, the vertebral compression fracture was not known clinically. In 18 patients, subsequent diagnosis of a compression fracture was determined by means of another imaging study (median interval, 7 months). At DXA, 39 (48%) of 81 patients with unreported vertebral body compression fractures had a nonosteoporotic T score (greater than -2.5). Most clinically important vertebral body compression fractures in nontrauma patients at risk for low bone mineral density may go unreported at abdominal multidetector CT if sagittal reconstructions are not routinely evaluated.


[Eating before of an unselected student population of the 7th to 10th grade in a Berlin school].
In 1990 a study of 32 girls and 44 boys in Grades 7 to 10 in a former "East Berlin" school in the borough of Prenzlauer Berg was carried out in continuation of an "East-West Berlin Study on Eating Disorders in Adolescents" which we had initiated in the mid-eighties. The Eating Attitudes Test (EAT), Eating Disorder Inventory (EDI), State of Comfort Scale (SCS) were used in a one-step study design together with complementary clinical and sociodemographic data, including body weight, height and BMI. On the whole, all students were well aware of their own body measurements and had definite ideas about their ideal body weight. Boys were less sure about their real weight, while girls showed some insecurity in defining their ideal weight. Regardless of weight parameters, girls were more strongly preoccupied with issues specific to eating disorders, such as dissatisfaction with their own body, the quest for a slim figure and diet. They were more severely affected by perceptions of insufficiency. 44% of all girls and 4% of the boys said they had problems with their body weight. These students' intensive preoccupation with issues specific to eating disorders was dependent on their actual body weight. They exhibited more clearly pronounced psychological characteristics of eating disorders. Eating-related and psychological characteristics of eating disorders were significantly more pronounced in girls with irregular menstruation. The correlation between irregular menstruation and individually perceived weight problems was significant. These results are discussed in greater detail with due consideration of the need for understanding the specific dynamics of eating attitudes in the general population.


[Incidence and significance of pathogen detection in Douglas fluid in non-inflammatory genital diseases].
Between 1976 and 1986 the secretions from the pouch of Douglas of 1,219 patients with non-inflammatory genital diseases were microbiologically studied. Microorganisms were detected in 3.4%. In the majority of cases they were physiological skin organisms, with a count of less than 10 per ml of Douglas fluid. These findings support the view, that secondary contamination of the specimens occurred during removal, transportation, or laboratory processing.


Anaplastic astroblastoma: a rare glial tumour.
Astroblastoma is a rarely diagnosed primary brain neoplasm whose histogenesis has been clarified recently. It occurs in children and young adults and presents as a well-circumscribed, contrast enhancing lesion in the cerebral hemisphere. Here the authors present a case of 25-year-old woman with an astroblastoma in the left frontal convexity that was excised. The characteristic radiological and histopathological features of this case are described. An astroblastoma should be included in the differential of a localised brain tumour, especially in a young patient.


Utility of basal and peak TSH values in TRH stimulation testing for predicting the long-term therapeutic prognosis of primary congenital hypothyroidism.
In Japan, most neonates undergo screening for congenital hypothyroidism (CH). A TRH stimulation test (TRH-T) may be performed after initial treatment as a useful method for reevaluating the patient's thyroid status. However, no studies have compared basal and peak TSH values in TRH-T in patients with long-term follow-up. This was a retrospective and observational study. The inclusion criteria were as follows: (1) CH diagnosis based on positive newborn screening, (2) follow-up > 15 yr, and (3) TRH-T after LT4 discontinuation. The participants were divided into a no-treatment group (No-T group) and a treatment group (T group). The No-T and T groups included 14 and nine patients, respectively. The age at TRH-T was 5.38 yr for the No-T group and 4.25 yr for the T group, with no significant difference. The basal and peak TSH levels were significantly lower in the No-T group. The areas under the Receiver operating characteristic curve for basal and peak TSH values were 0.984 and 0.905, respectively. When the basal TSH level was under 4.594 IU/mL, the No-T group had a sensitivity of 1.00 and a specificity of 0.93. Basal TSH levels alone may be sufficient for predicting the long-term therapeutic prognosis of patients with CH.


Alpha- and beta-band oscillations subserve different processes in reactive control of limb movements.
The capacity to rapidly suppress a behavioral act in response to sudden instruction to stop is a key cognitive function. This function, called reactive control, is tested in experimental settings using the stop signal task, which requires subjects to generate a movement in response to a go signal or suppress it when a stop signal appears. The ability to inhibit this movement fluctuates over time: sometimes, subjects can stop their response, and at other times, they can not. To determine the neural basis of this fluctuation, we recorded local field potentials (LFPs) in the alpha (6-12 Hz) and beta (13-35 Hz) bands from the dorsal premotor cortex of two nonhuman primates that were performing the task. The ability to countermand a movement after a stop signal was predicted by the activity of both bands, each purportedly representing a distinct neural process. The beta band represents the level of movement preparation; higher beta power corresponds to a lower level of movement preparation, whereas the alpha band supports a proper phasic, reactive inhibitory response: movements are inhibited when alpha band power increases immediately after a stop signal. Our findings support the function of LFP bands in generating the signatures of various neural computations that are multiplexed in the brain.


A mobile element on a virus particle surface identified by nuclear magnetic resonance spectroscopy.
The presence of a mobile element in the coat protein of pepper ringspot tobravirus (PRV) has been established by 1H n.m.r. spectroscopy; two-dimensional correlation spectroscopy (COSY) measurements show that this element consists of alanine, asparagine, glycine, proline, serine and threonine only. By reference to the amino acid sequence of the coat protein, it is concluded that the mobile element is associated with the C-terminal region and consists of between 11 and 38 residues.


[LIVER ORTHOTOPIC TRANSPLANTATION IN EXPERIMENTAL ANIMALS WITH VENO-VENOUS BYPASS PUMP HOSPITAL NACIONAL EDGARDO REBAGLIATI MARTINS-HNERM- 09/1996 TO 07/1998]
This study was carried at at the Hospital Nacional Edgardo Rebagliati Martins, from September 1996 to July 1998. 61 surgical procedures were performed in experimental animals, 39 in dogs and 22 in pigs. During the anhepatic phase, we used veno-venous bypass with centrifugal pumps and without systemic anticoagulation drugs in 6 animals, and passive venovenous bypass with systemic anticoagulation drugs in 8 animals. Experimental animals were sacrified two hours after the procedures were concluded in order to assess the status of vascular anastomosis and thrombus formation.


Relative contributions of perceived mattering to parents and friends in predicting adolescents' psychological well-being.
Perceived mattering is the psychological tendency to perceive the self as significant to specific other people. The central goal of this study was to examine whether adolescents' perceived mattering across social spheres (parents and friends) is addtive or compensatory in predicting adolescents' psychological well-being. Tests of the relative importance of adolescents' perceived mattering to parents and friends for psychological well-being were conducted using data from two convenience samples. Study 1 participants were, on the average, 17.5 yr. old and living in rural northwestern United States (N=128, 50% male, n=64; 50% female, n=64). Study 2 participants, on the average, were 16.9 yr. old, from a suburban western Canadian region (N=532, 51.4% male, n=273; 48.6% female, n=259). Hierarchical regression analysed with indicators of self-concept and behavioral misconduct as dependent variables used perceived mattering to parents and perceived mattering to friends and the interaction between these two variables as independent variables. Perceived mattering in both social spheres seemed the optimal condition for adolescents. Perceived mattering to friends "added" to perceived mattering to parents in explaining variance in assessments of psychological well-being in both studies.


Role of the Extremolytes Ectoine and Hydroxyectoine as Stress Protectants and Nutrients: Genetics, Phylogenomics, Biochemistry, and Structural Analysis.
Fluctuations in environmental osmolarity are ubiquitous stress factors in many natural habitats of microorganisms, as they inevitably trigger osmotically instigated fluxes of water across the semi-permeable cytoplasmic membrane. Under hyperosmotic conditions, many microorganisms fend off the detrimental effects of water efflux and the ensuing dehydration of the cytoplasm and drop in turgor through the accumulation of a restricted class of organic osmolytes, the compatible solutes. Ectoine and its derivative 5-hydroxyectoine are prominent members of these compounds and are synthesized widely by members of the Bacteria and a few Archaea and Eukarya in response to high salinity/osmolarity and/or growth temperature extremes. Ectoines have excellent function-preserving properties, attributes that have led to their description as chemical chaperones and fostered the development of an industrial-scale biotechnological production process for their exploitation in biotechnology, skin care, and medicine. We review, here, the current knowledge on the biochemistry of the ectoine/hydroxyectoine biosynthetic enzymes and the available crystal structures of some of them, explore the genetics of the underlying biosynthetic genes and their transcriptional regulation, and present an extensive phylogenomic analysis of the ectoine/hydroxyectoine biosynthetic genes. In addition, we address the biochemistry, phylogenomics, and genetic regulation for the alternative use of ectoines as nutrients.


LH and FSH response to synthetic LH-RH in children and adolescents with Turner's and Klinefelter's syndrome.
Stimulation with LH-RH (luteinizing hormone-releasing hormone) was performed in 29 children and adolescents with Turner's syndrome (15 less than 13 years old), and in 11 patients with Klinefelter's syndrome (7 before puberty). Synthetic LH-RH was injected intravenously in a dose of 25 mug/m2; plasma LH and FSH were determined radioimmunologically. The results show that patients with Turner's syndrome had pathologically elevated LH and FSH values at all ages. Normal LH and FSH results before and after LH-RH were found in 3 patients with X0/XX karyotype who had spontaneous menstruation. The 2 adult patients with Klinefelter's syndrome showed an exaggerated LH response and excessively high FSH levels before and after LH-RH, consistent with hypergonadotropic hypogonadism. Six out of 7 prepubertal boys with Klinefelter's syndrome, had a normal LH and FSH response to LH-RH. Only 1 prepubertal boy with cryptorchidism and genital maliformation in addition to the Klinefelter's syndrome had pathological values. The normal gonadotropin results in prepubertal patients with Klinefelter's syndrome show that their testes apparently loose the negative feedback activity on gonadotropin secretion only during puberty, at a time when tubular hyalinization appears. This is in contrast to Turner patients with gonadal dysgenesis who have hypergondadotropic hypogonadism already early in childhood.


Technical Feasibility and Safety of a Snare-Less, EVAR-First Technique for Iliac Branch Endoprosthesis.
The purpose of this study was to evaluate the technical feasibility, safety, and early outcomes of a snare-less, endovascular abdominal aortic aneurysm repair (EVAR)-first technique (SET) for iliac branch endoprosthesis (IBE) placement. We retrospectively reviewed all patients who received IBEs between July 2018 and March 2022. Patients were divided into 2 categories based on method of IBE deployment: SET or Standard. Primary endpoints were technical success, major adverse events, mortality, reintervention, internal iliac artery (IIA) patency, and freedom from IIA branch instability. Technical success was defined by successful deployment of both the EVAR and the IBE with maintained patency of the IIA and no stent graft migration. There were 20 patients (90% male, median age 72 [65.4-74.5] years) who underwent IBE placement. Among these, 5 (33.3%) underwent SET to treat 5 common iliac artery (CIA)/IIA aneurysms, while the remaining 15 (66.7%) underwent standard IBE deployment with through-and-through femoral access (n=13) or trans-brachial access (n=2) to treat 19 CIA/IIA aneurysms. Overall median renal to iliac bifurcation length was 169 (152-177) mm, with 9 patients falling short of the minimum of 165 mm for on-label IBE placement. Median contrast used was 148 (120-201) mL, fluoroscopy time 42.8 (35.0-49.8) minutes, estimated blood loss 200 (100-275) mL, and procedure time 192 (167-246) minutes, with no significant differences between the 2 groups. Technical success was achieved in 100% of cases. At 30 days, there were no mortalities or major adverse events in either group; there were 100% IIA patency, no IIA instability, and no reinterventions in both groups. Median follow-up in the SET group was 5.7 (5.5-6.2) months, with 1 death at 6 months and 1 type 1B endoleak at 6 months requiring reintervention. Median follow-up for the Standard group was 1.6 (0.8-2.1) years with 2 non-aneurysm-related deaths and no reinterventions at 1 year. SET for IBE is a safe and effective approach that decreases technical complexity and mitigates anatomic barriers to IBE placement. SET for IBE is a safe and effective approach to IBE placement that decreases technical complexity. A critical component to this technique is a large bore sheath with a stiff steerable tip. Importantly, this approach also mitigates anatomic barriers to IBE placement, expanding applicability of IBE technology to patients who may be otherwise ineligible.


Enhancing the branching ratios in the dissociation channels for O(16)O(16)O(18) molecule by designing optimum laser pulses: A study using stochastic optimization.
We propose a strategy of using a stochastic optimization technique, namely, simulated annealing to design optimum laser pulses (both IR and UV) to achieve greater fluxes along the two dissociating channels (O(18) + O(16)O(16) and O(16) + O(16)O(18)) in O(16)O(16)O(18) molecule. We show that the integrated fluxes obtained along the targeted dissociating channel is larger with the optimized pulse than with the unoptimized one. The flux ratios are also more impressive with the optimized pulse than with the unoptimized one. We also look at the evolution contours of the wavefunctions along the two channels with time after the actions of both the IR and UV pulses and compare the profiles for unoptimized (initial) and optimized fields for better understanding the results that we achieve. We also report the pulse parameters obtained as well as the final shapes they take.


Surgical Treatment of Cervical Radiculopathy: Meta-analysis of Randomized Controlled Trials.
Meta-analysis of published randomized controlled trials (RCTs). To determine whether anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR), or minimally invasive posterior cervical foraminotomy (MI-PCF) provides the best outcomes for patients with symptomatic single-level, single-side, and cervical radiculopathy. The surgical treatment of cervical radiculopathy is still controversial. ACDF has been widely used as a "gold standard." CDR has evolved and become a motion-preserving alternative with a potentially lower incidence of adjacent segment disease. However, both techniques require anterior neck dissection that carries a potential for serious morbidity. MI-PCF is a motion-preserving technique that can be performed with minimal invasiveness but has not gained universal acceptance. Electronic database search for RCTs comparing the efficacy and effectiveness of ACDF, CDR, and MI-PCF was performed. Meta-analysis was done for secondary surgical procedures and adverse events. A total of 358 studies were retrieved, of which four RCT reports met the inclusion criteria for this study. Three studies present clinical data comparing ACDF and CDR, and one study presents data comparing ACDF and MI-PCF. Available data from the RCTs analyzed concluded that ACDF, CDR, and MI-PCF result in significant improvements in relevant symptoms, clinical, and functional outcomes in patients with single-level, single side cervical radiculopathy refractory to nonoperative treatment. CDR had the lowest percentage of secondary surgical procedures (P = 0.0178) whereas MICPF had the lowest percentage of adverse events (P < 0.0001). All three techniques are effective in treating cervical radicular symptoms. MI-PCF has the lowest rate of adverse events whereas CDR has the lowest rate of secondary procedures. There is insufficient evidence to show which technique is the most effective and provides the longest-lasting symptom relief. 1.


Clinical Characteristics of Chronic Perforated Otitis Media in Different Age Groups.
We aimed to analyze preoperative and intraoperative clinical characteristics of chronic perforated otitis media by patient age. We analyzed 137 tympanoplasties for chronic perforated otitis media in 133 patients. Exclusion criteria were ear adhesions, cholesteatoma, and a history of tympanoplasty. Patients were divided into a younger group (aged 15-39 years), a middle group (40-64 years), and an elderly group (≥65 years). We compared tympanoplasty technique (using Wullstein classification), mastoid air-cell area measured by temporal bone computed tomography, preoperative aeration of the temporal bone, mean preoperative hearing (at 500 Hz, 1000 Hz, and 2000 Hz), and patch effect calculated by the pre- and post-patch air-bone gap at frequencies of 250 Hz and 500 Hz among the three age groups. Although type I tympanoplasty was performed most frequently in all age groups, it was performed significantly less often in the elderly group (p<0.05). The mean mastoid pneumatization index was significantly lower in the elderly group (p<0.05). Preoperative air-conduction hearing and bone-conduction hearing differed significantly among age groups (p<0.05 for both). There were no significant differences in the air-bone gap among the three groups. The mean patch effect was significantly better in the younger group than in middle or elderly groups (p<0.05). The less pneumatized mastoid and ossicular diseases in elderly patients with chronic perforated otitis media suggest that they had longer lasting and more severe childhood middle ear pathologies than did younger patients.


GABA attenuates amyloid toxicity by downregulating its endocytosis and improves cognitive impairment.
GABA (gamma-aminobutyric acid) receptor modulators have been investigated as a potential treatment strategy in Alzheimer's disease (AD). In the present study, we found that GABA levels were different in wild type (WT) and AβPP/PS1 mouse brains. GABA downregulated amyloid-β (Aβ) uptake in neurons through the receptor for advanced glycation end-products. Therefore, relative high levels of GABA decreased cytotoxicity induced by Aβ in WT mice. GABA treatment decreased basal levels of cell death and the cell death induced by hydrogen peroxide in WT and AβPP/PS1 neurons. Application of GABA during early life before 2 months of age can improve cognitive function significantly in AβPP/PS1 mice. However, GABA treatment at 6 and 8 months of age cannot improve water maze performance. Activating or suppressing GABAA receptors by optogenetic methods also confirmed that GABA activation before 2 months of age increased water maze performance in AβPP/PS1 mice. Our data suggest that GABA administration during early life can be a potential treatment for AD.


Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection.
Passage of helminth larvae through the lungs can cause pulmonary eosinophilia that may have evolved as a means of parasite attrition. If allergic responses represent a misdirected activation of this arm of the immune system, then mechanisms governing eosinophil recruitment during infection would be expected to be closely related to those seen in allergy. We studied primary Necator americanus infection and compared this to multiply-infected or vaccinated mice. The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which was greatly enhanced in previously sensitized mice. Interestingly, the presence of larvae in the lung was sufficient to trigger eosinophil chemoattractant production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced by prior exposure to the parasites. Infection stimulated IL-5 production in all groups; however, this and IgE production were greatly enhanced in sensitized animals. Elevated IL-5 increased bone marrow production of eosinophils, and eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore, trapping of larvae in the pulmonary vasculature is sufficient to trigger eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2 immunity does not increase local chemokine production, but does increase IL-5 production, which greatly enhances the availability of eosinophils for recruitment to the lung.


Influence of body condition and bovine somatotropin on estrous behavior, reproductive performance, and concentrations of serum somatotropin and plasma fatty acids in postpartum Brahman-influenced cows.
Ninety-nine multiparous Brahman-influenced (1/4 to 3/8 Brahman) cows were managed to achieve low (BCS = 4.3 +/- 0.1; n = 50) or moderate (BCS = 6.1 +/- 0.1; n = 49) body condition (BC) to determine the influence of bovine somatotropin (bST) on estrous characteristics, reproductive performance, and concentrations of serum GH and plasma NEFA. Beginning 32 d postpartum, cows within each BC were assigned randomly to treatment with or without bST. Non-bST-treated cows received no treatment, and treated cows were administered bST (Posilac, 500 mg s.c.) on d -35, -21, and -7 before initiation of the breeding season. On d -7, all cows received an intravaginal, controlled internal drug-releasing (CIDR) device. On d 0 (initiation of the 70-d breeding season), the CIDR were removed and cows received prostaglandin F2alpha (PGF2alpha). Blood samples were collected from the median caudal vein of the cows at each bST treatment and at d -28 and 0. Estrous behavior was monitored by radiotelemetry during the first 30 d of the breeding season. Growth hormone was increased (P < 0.05) in low and moderate BC cows treated with bST. The percentage of cows detected in estrus during the first 30 d of the breeding season was decreased (P = 0.05) for low BC (64%) compared with moderate BC (82%) cows. The interval to first estrus tended (P = 0.07) to be shorter in low BC-bST-treated cows (3.7 +/- 1.9 d) than in moderate BC-bST-treated cows (9.6 +/- 1.8 d). During the first 30 d of the breeding season, cows in low BC had a decreased (P = 0.02) number of mounts received and increased (P = 0.001) quiescence between mounts compared with cows in moderate BC. The number of mounts received was reduced (P = 0.04) in bST-treated cows. More (P = 0.02) cows treated with bST became pregnant during the first 3 d of the breeding season compared with non-bST-treated cows. The cumulative first-service conception rate tended (P = 0.07) to be greater for bST-low BC cows than non-bST-treated cows in low or moderate BC. On d 0, NEFA were greater (P < 0.05) in bST-treated vs. non-bST-treated cows. Low BC and bST reduced the intensity of behavioral estrus in postpartum Brahman-influenced cows. However, bST increased the first-service conception rate during the first 30 d of breeding and pregnancy rates during the first 3 d of breeding in postpartum Brahman-influenced cows.


Improvements in the Tolerability Profile of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in Parallel with Advances in Design, Screening, and Other Methods.
The development process of antisense oligonucleotides (ASOs) as therapeutic agents in humans has advanced through the implementation of chemical compound modifications as well as increasingly sophisticated toxicological preclinical screening techniques. The Ionis Integrated Safety Database was utilized to determine if advances in ASO screening and clinical lead identification methods have improved the tolerability profiles of 2'-O-methoxyethyl (2'MOE)-modified ASOs as a class, relative to the first 2'MOE ASO approved for use in humans, mipomersen. Tolerability was assessed by the incidence and percentage of subcutaneous doses leading to adverse events at the injection site or flu-like reactions (FLRs), as well as by the incidence of dose discontinuations due to these events. In randomized placebo-controlled phase 1 and phase 2 trials, the incidence of each measure of tolerability was lower in the test group of 12 ASOs (713 ASO-treated subjects) compared with the reference, mipomersen (266 ASO-treated subjects); with the most marked reduction in the incidence of FLRs (0.6% vs. 9.4%). A similar reduction in the incidence of dose discontinuation due to FLRs was also observed (0.2% vs. 0.9%). When compared with mipomersen, 8 of 12 ASOs showed significant improvements in their respective mean percentage of doses leading to adverse events at the injection site, whereas 7 ASOs showed a significant improvement in mean percentage of doses leading to FLRs. These results support an overall improvement in the tolerability profile in 2'MOE ASOs that entered development after mipomersen, in parallel with advances in the drug discovery screening process as well as the gains in clinical experience during development of each ASO.


Comparative evaluation of lesion development, tissue damage, and cytokine expression in golden hamsters (Mesocricetus auratus) infected by inocula with different Leishmania (Viannia) braziliensis concentrations.
The golden hamster (Mesocricetus auratus) is a susceptible model to Leishmania (Viannia) spp.; however, available studies employ different infection protocols, which account for clinical and pathological presentation differences. Herein, L. (V.) braziliensis preparations were standardized to contain 10(4), 10(5), or 10(6) parasites to determine an optimal inoculum that ensured cutaneous lesions without causing a disseminated infection in hamsters. Lesion development was followed for 105 days by size measurements, and skin, draining lymph node, spleen, and sera were investigated to check parasite load, spleen visceralization, cytokine expression, histopathological changes, and anti-Leishmania IgG levels. The lesion emergence time was inversely proportional to the parasite concentration in the inocula. Animals infected by 10(4) parasites presented nodular lesions, while those infected with 10(6) parasites often exhibited ulcerated lesions. The differences in the final lesion sizes were observed between 10(4) and 10(5) inocula or 10(4) and 10(6) inocula. High IFNG expression, anti-Leishmania IgG levels, and parasite load occurred independently of the inoculum used. A mild inflammatory skin involvement was observed in animals infected with 10(4) parasites, while extensive tissue damage and parasite spleen visceralization occurred with 10(5) and 10(6) parasites. These results indicate that inocula with different concentrations of parasites generate differences in the time of lesion emergence, clinical presentation, and systemic commitment, despite high and similar IFNG expression and parasite load. This suggests that a modulation in the immune response to different parasite numbers occurs in an early phase of the infection, which could dictate the establishment and magnitude of the chronic phase of the disease.


High-Quality CH3NH3PbI3 Films Obtained via a Pressure-Assisted Space-Confined Solvent-Engineering Strategy for Ultrasensitive Photodetectors.
High-quality organic-inorganic hybrid perovskite films are crucial for excellent performance of photoelectric devices. Herein, we demonstrate a pressure-assisted space-confined solvent-engineering strategy to grow highly oriented, pinhole-free thin films of CH3NH3PbI3 with large-scale crystalline grains, high smoothness, and crystalline fusion on grain boundaries. These single-crystalline grains vertically span the entire film thickness. Such a film feature dramatically reduces recombination loss and then improves the transport property of charge carriers in the films. Consequently, the photodetector devices, based on the high-quality CH3NH3PbI3 films, exhibit high photocurrent (105 μA under 671 nm laser with a power density of 20.6 mW/cm2 at 10 V), good stability, and, especially, an ultrahigh on/off ratio (Ilight/Idark > 2.2 × 104 under an incident light of 20.6 mW/cm2). These excellent performances indicate that the high-quality films will be potential candidates in other CH3NH3PbI3-based photoelectric devices.


[A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].
Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.


A novel splicing mutation in exon 4 (456G>A) of the GH1 gene in a patient with congenital isolated growth hormone deficiency.
Isolated Growth Hormone Deficiency (IGHD) due to GH1 gene defects has a variable inheritance pattern: autosomal recessive, autosomal dominant, and X-linked. the autosomal dominantly inherited form, IGHD II, is mainly caused by heterozygous mutations of splicing around the exon 3/IVs3 boundary region of the GH1 gene resulting in exon 3 skipping of transcripts. We have previously reported findings on GH1 gene mutations in 28 russian patients with severe congenital IGHD (-3.22+/-1.2 height sDs at the age of 1yr); five heterozygous dominant negative splice site mutations in intron 2, intron 3, and exon 4 of the GH1 gene were identified in 32.1% of the cohort. In the present report we describe a novel 456G>A heterozygous mutation of splicing of the last base of the 3'-acceptor splice site of exon 4 within the GH1 in a 4.2-year old, extremely short (-5.32 height sDs) girl with congenital IGHD. the mutation involves a highly conserved GGGgtg sequence of the exon 4/IVs4 boundary region of the GH1 gene. the predicted effect of the 456 G>A mutation is perturbed splicing with possible skipping of exon 4 of the GH1 gene. the novel heterozygous 456 G>A mutation in exon 4 expands the spectrum of dominant negative splicing defects within the GH1 gene, responsible for congenital IGHD.


Relationships between dental hygienists' career attitudes and their retention of practice. Part II. From the results of the Ohio Dentist and Dental Hygiene Surveys.
This article utilizes findings from the Ohio Dental Hygiene Survey and Ohio Dentist Survey to uncover what specific dental hygiene attitudes exist relative to employment and what factors have led to job termination and to re-entry. Ohio dental hygiene employees are most satisfied with patient relationships, co-worker relationships, and flexible working hours. The dental hygienists are least satisfied with fringe benefits, financial growth, and career creativity. Salary, benefits, nor career longevity were significant factors in determining satisfaction. Dental hygienists who were not working when surveyed, said they would consider returning to practice if a better salary were available, if they could find part-time work, if there were a good wage scale with benefits, or if their own financial need changed. Thirty-six percent of the non-practitioners said they would not ever consider returning to practice due to working conditions, establishment of a new career, or inadequate compensation. Dentist employers stated that they were satisfied or very satisfied with their dental hygienists' patient care and contribution to the practice.


In vivo modulation of human lymphocyte Fc gamma-receptors in response to oral antigen (cows' milk) challenge.
Following consumption of 1.2 litres of cows' milk by normal human adults there was a rapid fall in the proportion of peripheral blood lymphocytes bearing receptors for the reacted Fc of IgG (Fc gamma-receptors). This phenomenon was transient and apparently confined to the lymphocyte Fc gamma-receptor+ve subpopulation. Similar observations were made in rats but only in those animals pre-exposed to cows' milk suggesting that an immunological mechanism is involved. In man it was found that Fc gamma-receptors could only be re-expressed following incubation of post-milk lymphocytes in normal human serum. It is proposed that rapid in vivo modulation of lymphocyte Fc gamma-receptors occurs following oral antigen (cows' milk) challenge probably mediated by soluble food antigen-antibody complexes. The subsequent recovery of these receptors in vivo and in vitro may be due to the binding of 'fluid-phase' Fc gamma-receptors found in normal human serum.


Mitigation of inbreeding while preserving genetic gain in genomic breeding programs for outbred plants.
Heuristic genomic inbreeding controls reduce inbreeding in genomic breeding schemes without reducing genetic gain. Genomic selection is increasingly being implemented in plant breeding programs to accelerate genetic gain of economically important traits. However, it may cause significant loss of genetic diversity when compared with traditional schemes using phenotypic selection. We propose heuristic strategies to control the rate of inbreeding in outbred plants, which can be categorised into three types: controls during mate allocation, during selection, and simultaneous selection and mate allocation. The proposed mate allocation measure GminF allocates two or more parents for mating in mating groups that minimise coancestry using a genomic relationship matrix. Two types of relationship-adjusted genomic breeding values for parent selection candidates ([Formula: see text]) and potential offspring ([Formula: see text]) are devised to control inbreeding during selection and even enabling simultaneous selection and mate allocation. These strategies were tested in a case study using a simulated perennial ryegrass breeding scheme. As compared to the genomic selection scheme without controls, all proposed strategies could significantly decrease inbreeding while achieving comparable genetic gain. In particular, the scenario using [Formula: see text] in simultaneous selection and mate allocation reduced inbreeding to one-third of the original genomic selection scheme. The proposed strategies are readily applicable in any outbred plant breeding program.


HLA-G: At the Interface of Maternal-Fetal Tolerance.
During pregnancy, semiallogeneic fetal extravillous trophoblasts (EVT) invade the uterine mucosa without being rejected by the maternal immune system. Several mechanisms were initially proposed by Peter Medawar half a century ago to explain this apparent violation of the laws of transplantation. Then, three decades ago, an unusual human leukocyte antigen (HLA) molecule was identified: HLA-G. Uniquely expressed in EVT, HLA-G has since become the center of the present understanding of fetus-induced immune tolerance. Despite slow progress in the field, the last few years have seen an explosion in our knowledge of HLA-G biology. Here, we critically review new insights into the mechanisms controlling the expression and function of HLA-G at the maternal-fetal interface, and discuss their relevance for fetal tolerance.


Hormonal control of bone collagen synthesis in vitro: effects of parathyroid hormone and calcitonin.
The effects of parathyroid hormone (PTH) on bone collagen synthesis were assessed in organ cultures of fetal rat calvaria by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and non-collagen protein (NCP) using purified bacterial collagenase. 1) PTH decreased the incorporation of labeled proline into CDP at concentrations similar to those which stimulate bone resorption in vitro. 2) This effect was observed in bones treated for 6 h, but not for 3 h; it was maximal at 24 h and was maintained for 96 h. Bones treated with PTH for 48 h and transferred to control media for 48 h showed recovery of CDP labeling to control values. 3) the effect was specific for bone collagen. There was little alteration in the incorporation of proline into NCP, and incorporation into collagen was not inhibited. 4) The effect could be ascribed to decreased collagen synthesis and not to changes in amino acid uptake, precursor pool size, or degradation of newly synthesized CDP. In 3 hour experiments, PTH did increase the labeling of CDP and NCP, but only at tracer concentration of proline in the medium, compatible with an early stimulation of amino acid uptake. 5) Similar inhibition was observed with purified bovine (1-84) PTH and synthetic bovine PTH (1-34) as well as with crude homologous PTH obtained from rat parathyroid gland culture fluid. Human (hCT) and salmon (sCT) calcitonin did not inhibit the effect of PTH on the labeling of CDP nor did they stimulate CDP labeling directly at concentrations which inhibited bone resorption. Dibutyryl cyclic-3',5'-adenosine monophosphate (D3cAMP) inhibited labeling of CDP at concentrations of .03 to .3 mM, thus mimicking the action of PTH. However, in this system DBcAMP inhibited 45Ca release, thus mimicking CT. We conclude that the direct effect of PTH on bone collagen synthesis is a slow reversible inhibition, not opposed by CT. This effect may be mediated by cAMP formation in bone cells.


Diltiazem multi-dose gastrointestinal diffusion system: preparation and release rate studies.
The present paper is concerned with a multi-dose gastrointestinal diffusion system, releasing diltiazem through a controlled source of diffusional energy. The method calls for: a) encapsulation of the drug in a microball form, and b) coating of the resulting microballs by a porous membrane which controls the diffusion rate of the drug. The system would be expected to deliver the drug at a declining rate, due to the lower solubility of diltiazem hydrochloride in the intestinal than in the stomach fluid. To maintain a constant drug diffusion rate in the intestinal fluid, a membrane-modifying agent soluble in the intestinal tract (EudragitR L.) was introduced into the cellulose acetate microball coating. In this paper in vitro studies of drug release from the unit in relation to microball coating and coating mass are presented. The system provides a zero-order drug deliver in vitro, as the result of an appropriate selection of manufacturing parameters.


Characterization of a spontaneously transformed chicken mononuclear cell line.
We describe the characterization of a spontaneously transformed chicken monocytic cell line that developed as a single colony of cells in a heterophil culture that was inadvertently left in the incubator over a period of 25 days. These cells, hitherto named HTC, grow efficiently at both 37 or 41 degrees C in culture medium containing either 5% FBS or 2% chicken serum. The HTC cells are acid phosphatase positive, show expressions of both class I and class II major histocompatibility complex (MHC), CD44, K1, and K55 cell surface antigens, and engulf latex beads, produce nitrite and interleukin-6 on stimulation with bacterial lipopolysaccharide (LPS). Treatment with phorbol myristate acetate (PMA) induces respiratory burst in HTC cells and the secretion of matrix metalloproteinase (MMP) into culture medium. Using gene-specific primers and reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA trancripts for interferon-gamma (IFN-gamma), interleukin-1 (IL-1), interleukin-6 (IL-6), nitric oxide synthase (NOS), matrix metalloproteinase-2 (MMP-2), and transforming growth factor-beta (TGF-beta) were detected. Lipopolysaccharide (LPS) treatment of HTC cells modulated IL-1, IL-6, IFN-gamma, NOS mRNA levels as detected by RT-PCR analyses. Using different avian tumor virus gene-specific primers and PCR, the HTC cells were positive for the presence of avian leukosis virus (ALV) and Marek's disease virus (MDV) but negative for reticuloendothelial virus (REV), chicken infectious anemia virus (CIAV), and herpes virus of turkeys (HVT). The production of ALV antigens by HTC cells was further confirmed using p27 gag protein ELISA. Collectively, these results show that the HTC cells belong to myeloid/macrophage lineage and were likely transformed by ALV and MDV but retain many interesting and useful biological activities.


Treatment completion in a brief motivational intervention in the emergency department: the effect of multiple interventions and therapists' behavior.
The aim of this study was to identify therapist behaviors during a brief motivational intervention (BMI) given to injured emergency department patients that predicted participant return for a second BMI session and 12-month alcohol-related outcomes. This was a secondary data analysis of a randomized controlled trial (n = 539) previously demonstrating that random assignment to a BMI and booster session resulted in a significant reduction of 12-month post-intervention alcohol-related injuries and negative consequences relative to standard care. Participants who actually received 2 BMI sessions had significantly less alcohol-related negative consequences than those who received only 1 BMI session. Therapists who reported a higher focus on emotional support and low focus on participant drinking behaviors during the initial BMI session were more likely to have assigned participants return for the second BMI session. The results of these secondary analyses show that compliance with a 2-session therapeutic intervention (BIB) predicted fewer negative alcohol-related consequences, and that therapists' supportive emotional emphasis during the first BMI session was important in predicting participants returning for the second MI session.


Effectiveness of difluprednate in addition to systemic therapy for the treatment of anterior scleritis.
To describe the effectiveness and side-effect profile of adding difluprednate therapy to patients with anterior scleritis being treated systemically. Retrospective chart review. Charts from all patients with anterior scleritis who were treated with topical difluprednate in addition to systemic therapy from 1 January 2018 to 1 January 2020 were reviewed. Data collected included: demographics, scleritis type, systemic diagnosis, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, type of systemic treatment used, best-corrected visual acuity (BCVA) and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery and IOP ≥24 mm Hg. Thirty-two patients (44 eyes) were analysed. The median age was 57 years (IQR 52, 72); 59% were female; 72% were Caucasian. An associated systemic disease was present in 59%. Systemic therapies used when difluprednate was added were: 65% immunosuppressive agents, 43% prednisone and 25% non-steroidal anti-inflammatory drugs. The addition of difluprednate resulted in clinical resolution in 79.6% of the treated eyes. Median time to inactivity was 9 weeks (IQR 5, 20). Eyes initially using 2-4 drops per day had a higher response rate (89%, p=0.005). Over a median follow-up of 34 weeks (IQR 21, 74), 11 eyes had IOP elevation; 6 eyes lost ≥2 lines of BCVA, 5 eyes had cataract progression. Most eyes treated with difluprednate achieved inactivity. The addition of difluprednate to systemic therapies provides an alternative to achieve control of inflammation.


Analysis of the Imprinting Status and Expression of the MAGEL2 Gene During Initiation at Puberty in the Dolang Sheep.
Genomic imprinting refers to the expression of parent-specific genes in diploid mammalian cells. MAGEL2 gene is a maternally imprinted gene that has been identified in mice and humans and is associated with the onset of puberty. The purpose of this study was to investigate its imprinting status and its relationship with the onset of puberty in Dolang sheep. The sequence of 3734 bp cDNA of MAGEL2 in Dolang sheep was obtained by cloning and sequencing, encoding 1173 amino acids. The results of the nucleotide and amino acid similarity analysis showed that it was highly conserved among different mammalian species. The MAGEL2 gene was expressed monoallelically in the tissues of adult and neonatal umbilical cords, and the expressed allele was paternally inherited. Real Time quantitative PCR (RT-qPCR) results showed that the MAGEL2 gene was highly expressed in the hypothalamus and pituitary gland, increased significantly from prepuberty to puberty, and decreased significantly after puberty. This study suggests that MAGEL2 is a paternally expressed and maternally imprinted gene in Dolang sheep, which may be involved in the initiation of puberty in Dolang sheep. This study provides a theoretical basis for further research on the mechanism of the imprinted gene MAGEL2 regulating the onset of puberty in sheep, and provides a new idea for the future research on the mechanism of onset of puberty in sheep.


Exosomal miRNA signatures of pancreatic lesions.
Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development. A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n = 58), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH). Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes. This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.


Visual Illusion Created by a Striped Pattern through Augmented Reality for the Prevention of Tumbling on Stairs.
A fall on stairs can be a dangerous accident. An important indicator of falling risk is the foot clearance, which is the height of the foot when ascending stairs or the distance of the foot from the step when descending. We developed an augmented reality system with a holographic lens using a visual illusion to improve the foot clearance on stairs. The system draws a vertical striped pattern on the stair riser as the participant ascends the stairs to create the illusion that the steps are higher than the actual steps, and draws a horizontal striped pattern on the stair tread as the participant descends the stairs to create the illusion of narrower stairs. We experimentally evaluated the accuracy of the system and fitted a model to determine the appropriate stripe thickness. Finally, participants ascended and descended stairs before, during, and after using the augmented reality system. The foot clearance significantly improved, not only while the participants used the system but also after they used the system compared with before.


Development of Poly(lipoic acid) Nanoparticles with Improved Oral Bioavailability and Hepatoprotective Effects of Quercetin.
Quercetin (QUE)-loaded poly(lipoic acid) nanoparticles (QUE/pLA) were developed to improve chemical stability in the gastrointestinal (GI) tract, oral bioavailability (BA), and pharmacological properties of QUE. QUE/pLA was prepared by emulsion solvent evaporation with ultrasonication followed by freeze-drying. Its mean particle size was 185 nm, with a high encapsulation efficiency of QUE (84.8%). QUE/pLA exhibited sustained release of QUE with improved dissolution compared with crystalline QUE and significantly enhanced chemical stability under physiological pH in the GI tract. Orally dosed QUE/pLA (50 mg QUE/kg) in rats exhibited significantly prolonged systemic exposure, possibly due to the sustained release of QUE. The oral BAs of QUE in QUE/pLA and crystalline QUE groups were 29 and 0.19%, respectively, suggesting significant enhancement of oral absorbability, likely due to the improved stability and dissolution property of QUE in the GI tracts. In hepatic injury model rats, QUE/pLA (50 mg QUE/kg) led to marked reductions in the plasma biomarker levels of alanine aminotransferase and aspartate aminotransferase by 70 and 46%, respectively, compared with the vehicle group. QUE/pLA also showed improved antioxidant potential as evidenced by the enhanced activities of hepatic glutathione, superoxide dismutase, and a decrease in the level of malondialdehyde, a marker of lipid peroxidation. Based on these findings, QUE/pLA might be a promising option to improve both the nutraceutical and pharmaceutical properties of QUE.


Antibody levels to recombinant tick calreticulin increase in humans after exposure to Ixodes scapularis (Say) and are correlated with tick engorgement indices.
The antibody responses of subjects who presented with a definite Ixodes scapularis (Say) tick bite were measured to determine the utility of the antibody response against recombinant tick calreticulin (rTC) as a biologic marker of tick exposure. Subjects bitten by I. scapularis evidenced an increase in anti-rTC antibody levels between visit 1 and visit 2 from 24.3 to 27.1 ng/microl serum (n = 88, p = 0.003), and levels remained elevated at visit 3 (p = 0.005). These anti-rTC antibody levels during visits 2 and 3 were significantly higher than those in four non-exposed controls. Tick engorgement indices, measured on the biting ticks, were found to be correlated with anti-rTC antibody levels (e.g., for visit 3: Pearson's r = 0.357, p = 0.001). Tick engorgement index (TEI), ratio of body length to scutal width, was identified to be the only independent predictor of anti-rTC antibody levels in linear regression models. Logistic regression revealed that a bite from an I. scapularis tick that became engorged (TEI >3.4) was a risk factor for anti-rTC antibody seropositivity (adjusted odds ratio for age and bite location = 7.4 (95% confidence interval 2.1-26.4)). The anti-rTC antibody test had a sensitivity of 0.50 and a specificity of 0.86 for a bite from I. scapularis that became engorged. Immunoblotting revealed that subjects made a specific anti-rTC antibody response.


Gastrointestinal biopsy in the horse: overview of collection, interpretation, and applications.
Evaluation of gastrointestinal (GI) biopsies is a multistep process that includes reviewing an appropriate history, determining sample quality, and evaluating histologic sections. Selected diagnostic parameters that, in combination with intestinal histopathology, can be useful to localize disease to the intestinal tract in the horse include hypoproteinemia and hypoalbuminemia, ultrasound evidence of increased thickness of the small intestinal wall, and alterations in glucose or D-xylose absorption tests. Biopsies may be acquired either endoscopically, or via laparoscopy or standing flank incisional approaches. GI sections should be evaluated using a systematic approach that includes both architectural changes and inflammatory cell infiltrates. Although strategies have been developed for assessment of GI biopsies from the dog and cat, a standardized approach to interpretation of the equine GI biopsy has yet to be developed. GI biopsies pose several challenges to the pathologist, especially for endoscopic biopsies in which the quality of the specimen and its orientation may vary greatly. Architectural changes are arguably the most critical changes to evaluate. In a horse with chronic GI inflammation, such as occurs in idiopathic inflammatory bowel disease (IBD), the cell types encountered frequently are macrophages, eosinophils, lymphocytes, and plasma cells. Increased numbers of these cell types are categorized loosely as mild, moderate, and severe. Specific forms of idiopathic IBD have been further classified by this infiltrate as granulomatous enteritis, eosinophilic enteritis, and lymphoplasmacytic enteritis; there is limited information on microscopic changes with each. Unfortunately, microscopic GI lesions are usually nonspecific, and determination of etiology requires further investigation.


Anatomy and age estimation of an early blue whale (Balaenoptera musculus) fetus.
The external anatomy of a 130-mm blue whale fetus (Balaenoptera musculus) is described, and its internal anatomy is reconstructed noninvasively from microCT scans. The specimen lies developmentally at the junction of the embryonic and fetal periods. Similarly to the embryos of many odontocetes, it lacks a caudal fluke and dorsal fin, but it also exhibits an elongated rostrum, resorbed umbilical hernia, partially exposed cornea, and spatial separation of the anus and genitalia seen in early odontocete fetuses. Dermal ossification of the cranial bones has begun, but the endochondral skeleton is completely cartilaginous. The shape and position of the maxilla suggest that the earliest stages of anterior skull telescoping have begun, but there is no indication of occipital overlap posteriorly. The nasopharynx, larynx, and heart already display the distinctive morphology characteristic of Balaenoptera. This study develops a model of body length changes during blue whale development by integrating the large International Whaling Statistics (IWS) database, historical observations of blue whale migration and reproduction, and descriptions of fetal growth trends in other mammals. The model predicts an age of 65 days postconception for the specimen. The early developmental milestones of Balaenoptera mirror those of the odontocete Stenella to a remarkable extent, but the first appearance of the caudal fluke and dorsal fin are delayed relative to other morphological transitions. The accelerated prenatal growth characteristic of Balaenoptera occurs during fetal, not embryonic, development.


Chemical studies of essential oils of Juniperus oxycedrus ssp. badia.
Leaf and (unripe and ripe) berry essential oils of Juniperus oxycedrus ssp. badia (H. Gay) Debeaux grown wild in Spain have been analysed by capillary GC and GC-MS in combination with retention indices. A seasonal investigation of both leaf and berry oils was also performed. Among the approximately 80 constituents investigated (representing 90-98% of the oils) 60-68 were identified (80-97% of the oil composition). The leaf oils were mainly composed of alpha-pinene (40-57%) and manoyl oxide (5-10%). The (unripe) berry oils were dominated by alpha-pinene (65%) with moderate amounts of myrcene, limonene, germacrene D or gamma-muurolene. Several differences in yields and chemical composition from a qualitative and quantitative point of view were detected when comparing all the oil samples analysed. In addition, two oil samples were examined, but found inactive, against the replication of HIV-1(III(B)) and HIV-2(ROD) in cell culture, whereas the samples were toxic for the cells at a 50% cytotoxic concentration of 106 and 123 microg/ml, respectively.


[Experimental study of the inhibiting effect of the lentiviral vector mediated herpes simplex virus-thymidine kinase/ganciclovir on GVHD].
To study the effect of lentiviral vector mediated herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) on graft- versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo- BMT) in mice. Donor splenic lymphocytes from C57BL/6 which were infected by lentiviral vectors carrying HSV-TK were transplanted into 60Co gamma ray irradiated recipient mice with donor bone marrow cells. GCV 25 mg x kg(-1) x d(-1) was administered in 3 groups on day 0, +7, +12 respectively after transplant for 7 days by intraperitoneal injection. Survival time, severity of GVHD, incidence of GVHD, T lymphocytes immune reconstruction and of allogeneic chimerism ratio were detected after allo-BMT. The average survival times for GCV 0 day, +7 day and +12 day group were (30. 10 +/- 5.21) d, (36.40 +/- 5.28) d and (28.20 +/- 4.82) d respectively, being significantly longer than that in the control group [(15.10 +/- 0.43) d] (P < 0.05). The 50 d-survival rate for TK/GCV + 7 day group was 60%. While for 0 day and +12 day group was 40% and 30% respectively. The incidence of grade III approximately IV GVHD in the control group was 100%, and the dead mice in experimental groups showed pathological changes of II approximately III GVHD. Long-term alive recipient mice only developed grade I approximately II GVHD after allo-BMT. The number of CD4+ lymphocytes in experimental groups was higher than that in control group (P <0.05), but CD8+ lymphocytes was lower on day +5, +10, +15 day (P <0.05). Allogeneic chimerism rate of recipient mice on +30 d was 100%. HSV-TK/GCV induced by the lentiviral vectors has a definite effect in prevention of GVHD after allo-BMT. GCV administrated from 7 days post-transplantation showed the best effects.


Effect of taping on spinal pain and disability: systematic review and meta-analysis of randomized trials.
Taping is a widely used therapeutic tool for the treatment of musculoskeletal disorders, nevertheless its effectiveness is still uncertain. The purpose of this study was to conduct a current review of randomized controlled trials (RCTs) concerning the effects of elastic and nonelastic taping on spinal pain and disability. MEDLINE, CINAHL, EMBASE, PEDro, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, ISI Web of Knowledge, and SPORTDiscus databases were searched. All published RCTs on symptomatic adults with a diagnosis of specific or nonspecific spinal pain, myofascial pain syndrome, or whiplash-associated disorders (WAD) were considered. Two reviewers independently selected the studies and extracted the results. The quality of individual studies was assessed using the PEDro scale, and the evidence was assessed using GRADE criteria. Eight RCTs were included. Meta-analysis of 4 RCTs on low back pain demonstrated that elastic taping does not significantly reduce pain or disability immediately posttreatment, with a standardized mean difference of -0.31 (95% confidence interval=-0.64, 0.02) and -0.23 (95% confidence interval=-0.49, 0.03), respectively. Results from single trials indicated that both elastic and nonelastic taping are not better than placebo or no treatment on spinal disability. Positive results were found only for elastic taping and only for short-term pain reduction in WAD or specific neck pain. Generally, the effect sizes were very small or not clinically relevant, and all results were supported by low-quality evidence. The paucity of studies does not permit us to draw any final conclusions. Although different types of taping were investigated, the results of this systematic review did not show any firm support for their effectiveness.


Heel Pain: Diagnosis and Management.
The differential diagnosis of heel pain is extensive, but a mechanical etiology is the most common. The specific anatomic location of the pain can help guide diagnosis. The most common diagnosis is plantar fasciitis, which leads to medial plantar heel pain, especially with the first weight-bearing steps after rest. Other causes of plantar heel pain include calcaneal stress fractures (progressively worsening pain after an increase in activity or change to a harder walking surface), nerve entrapment or neuroma (pain accompanied by burning, tingling, or numbness), heel pad syndrome (deep, bruise-like pain in the middle of the heel), and plantar warts. Achilles tendinopathy is a common cause of posterior heel pain; other tendinopathies result in pain localized to the insertion site of the affected tendon. Posterior heel pain can also be attributed to Haglund deformity (a prominence of the calcaneus that may lead to retrocalcaneal bursa inflammation) or Sever disease (calcaneal apophysitis common in children and adolescents). Medial midfoot heel pain, particularly with prolonged weight bearing, may be due to tarsal tunnel syndrome, which is caused by compression of the posterior tibial nerve. Sinus tarsi syndrome manifests as lateral midfoot heel pain and a feeling of instability, particularly with increased activity or walking on uneven surfaces.


miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF.
Endothelial cell migration induced in response to vascular endothelial growth factor (VEGF) is a crucial step of angiogenesis and it depends on the activation of the p38 MAP-kinase pathway downstream of VEGFR2. In this study, we investigated the role of microRNAs (miRNAs) in regulating these processes. We found that the VEGF-induced p38 activation and cell migration are modulated by overexpression of Argonaute 2, a key protein in the functioning of miRNAs. Thereafter, we found that miR-20a expression is increased by VEGF and that its ectopic expression inhibits VEGF-induced actin remodeling and cell migration. Moreover, the expression of miR-20a impairs the formation of branched capillaries in a tissue-engineered model of angiogenesis. In addition, the lentivirus-mediated expression of miR-20a precursor (pmiR-20a) is associated with a decrease in the VEGF-induced activation of p38. In contrast, these processes are increased by inhibiting miR-20a with a specific antagomir. Interestingly, miR-20a does not modulate VEGFR2 or p38 protein expression level. miR-20a does not affect either the expression of other known actors of the p38 MAP kinase pathway except MKK3. Indeed, by using quantitative PCR and Western Blot analysis, we found that pmiR-20a decreases the expression of MKK3 and we obtained evidence indicating that miR-20a specifically binds to the 3'UTR region of MKK3 mRNA. In accordance, the VEGF-induced activation of p38 and cell migration are impaired when the MKK3 expression is knocked down by siRNA. We conclude that miR-20a acts in a feedback loop to repress the expression of MKK3 and to negatively regulate the p38 pathway-mediated VEGF-induced endothelial cell migration and angiogenesis.


[Patient-controlled analgesia. PCA in a three year old child after traumatic amputation].
We report the case of a 3-year-old boy, who received long-term parent-controlled analgesia after traumatic amputation of one leg. He underwent surgery 17 times for a period of 25 days. Parent-controlled analgesia was started four days after admission because analgesia with non-opioid analgetics (acetaminophen) proved to be insufficient. The pump was set to a bolus-dose of 23 micrograms kg-1 piritramide (dipidolor) and a lockout interval of 10 minutes. Permitted maximum cumulative dose in four hours was 5 mg piritramide. There was no continuous infusion of opioid. PCA and possible adverse effects were explained to the mother. A monitoring regimen was used to assess efficacy (pain intensity estimated by the mother), adverse effects (sedation score, occurrence of nausea and vomiting) and piritramide consumption. For fear of side effects opioid administration was insufficient in the beginning. After three days the mother used the PCA effectively and no additional analgesic medication was required. Nausea or other side effects were not observed. After seven days opioid consumption nearly doubled. Apart from tolerance, this might have resulted from the mother's caution in the first days. After 17 days the PCA was discontinued. Oral analgetics (tramadol) controlled the pain adequately. Management of postoperative pain in children is difficult and too often insufficient. PCA is a safe and effective method of providing postoperative pain relief. Feasibility was shown in adolescents and, more recently, in children aged five years and over. Only few reports are available describing long term use of PCA in children younger than five years. Our case suggests that PCA may also be used effectively and safely in children younger than five years, if experienced staff, a monitoring regimen and cooperative and well instructed parents are available.


Evidence-based HIV pilot program for Chinese college students: Differences by gender.
This study explored gender differences in the effectiveness of the translated VOICES (Video Opportunities for Condom Education and Safer Sex) intervention on the condom use intention, perceived benefits and barriers to condom use, condom use self-efficacy, and HIV/AIDS knowledge among Chinese students in a US university. We utilized a pretest/post-test quasi-experimental design and recruited 67 Chinese students at the local university. Participants viewed a 20-min video with Chinese subtitles, attended one 25-min small group discussion and condom interactive educational activity. Female participants showed significantly greater mean scores of perceived benefits and condom use self-efficacy, in comparison with male participants. Female participants also reported significantly higher scores than male participants in five of the perceived benefits items and one self-efficacy item. These study results provide important information for developing more differentiated intervention strategies specific to gender for HIV and STI education programs.


Perinatal events associated with maternal smoking during pregnancy.
To identify components of smoking-related increased perinatal mortality, detailed analyses of data from the Ontario Perinatal Mortality Study (50,000 births, 1,300 deaths, 1960-1961) measured the relationship of maternal smoking to birth weight, gestation, placental complications, and perinatal mortality. Cross-tabulations with other factors and multiple adjustment showed increases with amount smoked of birth weights less than 2500 gm, gestations less than 38 weeks, placenta previa, abruptio placentae, and perinatal mortality. These significant, smoking-related increases were independent of mother's height, weight, hospital status, age-parity group, birthplace, previous pregnancy history, weight gain, time of registration, and sex of child. Maternal smoking had the strongest effect on birthweight in the 8 factor regression, and birth less than 2500 gm increased directly with smoking level from 20% to 340% in 37 data subgroups. Births less than 38 weeks increased 20% and 50% and perinatal mortality increased 20% and 35% for less than 1 pack and 1 + pack smokers, respectively, adjusted for 7 other factors. Placental complications increased consistently with smoking level in all of 37 subgroups except for primiparous less than 1 pack smokers. Adjusted rates increased 25% and 92% for placenta previa, 23% and 86% for abruptions among smokers of less than 1 pack and 1 + packs, respectively. These complications carry high perinatal mortality risk, and account for one-third to one-half of the perinatal deaths attributable to maternal smoking.


Combinatorial stress responses: direct coupling of two major stress responses in Escherichia coli.
Nitrogen is an essential element for all life, and this is no different for the bacterial cell. Numerous cellular macromolecules contain nitrogen, including proteins, nucleic acids and cell wall components. In Escherichia coli and related bacteria, the nitrogen stress (Ntr) response allows cells to rapidly sense and adapt to nitrogen limitation by scavenging for alternative nitrogen sources through the transcriptional activation of transport systems and catabolic and biosynthetic operons by the global transcriptional regulator NtrC. Nitrogen-starved bacterial cells also synthesize the (p)ppGpp effector molecules of a second global bacterial stress response - the stringent response. Recently, we showed that the transcription of relA, the gene which encodes the major (p)ppGpp synthetase in E. coli, is activated by NtrC during nitrogen starvation. Our results revealed that in E. coli and related bacteria, NtrC functions in combinatorial stress and serves to couple two major stress responses, the Ntr response and stringent response.


Responses of human hepatoma HepG2 cells to silver nanoparticles and polycyclic aromatic hydrocarbons.
The nanotechnology has revolutionized the global market with silver nanoparticles (AgNP) occupying a prominent position due to their remarkable anti-bacterial properties. However, there is no data about the adverse and toxic effects of associations of AgNP and ubiquitous compounds, such as polycyclic aromatic hydrocarbons (PAH). In the current study, we investigated the responses of HepG2 cells to realistic concentrations of AgNP (0.09, 0.9, and 9 ng ml-1) and mixture of PAH (30 and 300 ng ml-1), separately and in association. Cell viability and cytotoxicity (neutral red retention and MTT production assays) and proliferation (crystal violet [CV] assay), xenobiotic efflux transporter activity (rhodamine B accumulation assay), ROS levels (dichlorodihydrofluorescein diacetate assay), and lipid peroxidation (pyrenylphosphine-1-diphenyl assay) were analyzed. There was no decreases of cell viability after exposure to AgNP, PAH and most of AgNP + PAH associations, but increases of cell viability/number (CV assay) occurred. Efflux transporter activity was not affected, with exception of one AgNP + PAH associations, ROS levels increased, but lipid peroxidation decreased. Some toxicological interactions occurred, particularly for the highest concentrations of AgNP and PAH, but there is no evidence that these interactions increased the toxicity of AgNP and PAH.


Various Antioxidant Effects Were Attributed to Different Components in the Dried Blossoms of Citrus aurantium L. var. amara Engl.
Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as an edible and medicinal material in China. Total flavonoids (CAVAF), alkaloids (CAVAA), polysaccharides (CAVAP), coumarins (CAVAC), and neroli (CAVAO) were extracted from CAVA. Hesperidin, naringin, and neohesperidin composed 83.94% of CAVAF, and synephrine represented 50.56% of CAVAA. On the basis of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS• +), hydroxyl radical (•OH), ferric-reducing antioxidant power (FRAP), and reducing power assays, the antioxidant activities of five components were comprehensively and comparatively investigated. CAVAF had a stronger DPPH• scavenging effect and FRAP and reducing power. CAVAP and CAVAA exhibited comparable •OH scavenging effects to vitamin C. CAVAA showed the highest ABTS• + scavenging activity. In conclusion, different constituents varied significantly toward different sources of free radicals and other oxidants. It is obvious that CAVA has various antioxidant effects, which are attributed to different components.


Active compression-decompression CPR improves vital organ perfusion in a dog model of ventricular fibrillation.
This study was designed to assess whether a new method of cardiopulmonary resuscitation (CPR), termed active compression-decompression CPR, or ACD-CPR, improves organ perfusion when compared with standard (S) CPR in a dog model of ventricular fibrillation. ACD-CPR has recently been shown to improve hemodynamic and respiratory parameters during cardiac arrest when compared with standard CPR. However, to our knowledge, the effects of ACD-CPR on tissue perfusion have not been investigated. Ventricular fibrillation was induced in eight anesthetized, intubated animals. ACD-CPR and standard CPR were each performed twice in alternating order. All interventions were preceded by 1 min of ventricular fibrillation, in which no CPR was performed, and consisted of 6 min of CPR with either technique during which tissue perfusion was measured. Compressions were performed at 80/min with a 50 percent duty cycle and 175 to 200 N downward force applied to the chest wall for both techniques. Epinephrine was administered at the beginning of each 6-min CPR interval. Hemodynamic monitoring of aortic and right atrial pressure was performed continuously and myocardial, cerebral, and renal blood flows were measured using the radiolabeled microsphere technique at baseline and during all interventions. Baseline organ perfusion and hemodynamics were similar for all dogs. Baseline left ventricular, brain, and renal blood flows were 62.0 +/- 5.5, 14.1 +/- 2.1, and 476.3 +/- 55.5 ml/min/100 g, respectively (mean +/- SEM). Compared with standard CPR, ACD-CPR resulted in higher global left ventricular (22.5 +/- 6.2 vs 14.1 +/- 4.0 ml/min/100 g, p < 0.01), cerebral (12.0 +/- 2.4 vs 8.5 +/- 2.3 ml/min/100 g, p < 0.01), and renal cortical (27.8 +/- 5.0 vs 17.5 +/- 5.0 ml/min/100 g, p < 0.05) blood flows. Regional flows to the epicardium, endocardium, and midmyocardium as well as to the frontal, parietal, and occipital lobes of the brain were all significantly improved by ACD-CPR. Aortic systolic (61.7 +/- 4.1 vs 49.5 +/- 3.1 mm Hg, p < 0.01), aortic mean (31.6 +/- 2.8 vs 27.2 +/- 2.2 mm Hg, p = 0.001), and myocardial perfusion pressure (12.9 +/- 3.4 vs 10.4 +/- 3.4 mm Hg, ACD-CPR vs standard CPR, p < 0.01) were all higher during ACD-CPR than during standard CPR. We conclude that ACD-CPR improves tissue perfusion and systemic hemodynamics compared with standard CPR.


[Disseminated ovarian, bone, and bone marrow metastases from gastric cancer].
The main cause of death in patients with gastric cancer is disease dissemination. It is not clear why gastric cancer metastasizes to different organs. Early detection and destruction of circulating malignant cells before developing metastases may markedly improve survival of these patients. Krukenberg tumors (metastases of non-gynecological origin in the ovaries) usually are circular cell carcinomas of gastric cancer. Bone metastases of gastric cancer are rare, but if they are diagnosed, patients survive only 2-5 months on the average. Disseminated bone marrow metastases from gastric cancer do not always show the sudden course of the disease, but hematological complications are signs of poor prognosis. Hematological paraneoplastic disorders can be miscellaneous: they usually manifest as anemia of various origin, as leucocytosis in half of the patients, as leukemoid reactions in one-third of the patients, and as hemolysis and thrombocytopenia in half of the patients (often with disseminated intravascular coagulation). Currently, chemotherapy is the most effective treatment for outspread gastric cancer. Unfortunately, there is no exclusively effective scheme for treatment. Lymph node metastases are more sensitive to chemotherapy than primary gastric cancer, while in contrary, hepatic metastases are less sensitive than primary gastric cancer. This article includes a literature review and a rare case of gastric cancer.


Ethical evaluation of hypnosis research: a survey of investigators and their institutional review boards.
We surveyed hypnosis researchers and Institutional Review Boards (IRBs) with regard to the ethical evaluation of research protocols. Researchers and IRB administrators were independently surveyed within the same institutions. Both objective and free response items were used to address substantive issues such as deception and at-risk populations, as well as practical matters such as paperwork. Parallel questions allowed a point-counterpoint between researchers and IRBs. Overall, the results suggest that IRBs do not treat hypnosis research differently than other types of research. We end with recommendations for facilitating interactions between hypnosis researchers and their IRBs.


Crude tonsillectomy and local concepts of illness in Kisoro, Uganda: community perception of gapfura and its treatment.
The practice of crude tonsillectomy (CT), performed by traditional healers for a locally defined illness known as gapfura, has become increasingly common in south-western Uganda. This study describes perceptions of gapfura and examines the intersection of locally defined and biomedical illness. Kisoro District Hospital (KDH) staff (n=55) were surveyed, with 95% reporting that CT caused death, and 60% estimating that recipients died as a result of the procedure. Surveys of community members (n=737) revealed that 95% were familiar with gapfura as a common illness with variable symptoms; syndrome classification categorised 58% of descriptive responses as 'upper respiratory infection', while 42% suggested more severe diseases. Although only 26% of community respondents told the interviewer that CT was the best treatment, 47% believed the majority of community members use CT and 43% of those treated for gapfura within the past year received CT. The divergent perceptions of community members and allopathic health providers may be rooted in the use of gapfura as an idiom reflecting larger social stressors and CT as a response to this distress. Interventions to curb the practice of CT need to be multifaceted and will involve further anthropologic investigation, public health involvement, and education that encompasses the social context of disease.