Plasma osteoprotegerin concentrations in type 2 diabetic patients and its association with neuropathy.
To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy. Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject. Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels. The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.


Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology.
Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies. However, recent animal model data are incongruous with established paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development of effective interventions for RA-ILD.


Anxious attachment improves and is predicted by anxiety sensitivity in internet-based, guided self-help cognitive behavioral treatment for panic disorder.
The purpose of this study was to examine whether anxious and avoidant attachment styles improve during guided internet-based cognitive behavioral treatment (ICBT) for panic disorder, and if so, to identify potential theoretically driven mechanisms related to the change. We examined changes in anxious and avoidant attachment and their time-lagged (1 week), longitudinal relationship with panic-related constructs in patients participating in ICBT (n = 79) in an open trial. Anxious attachment scores improved significantly with a medium effect during ICBT, d = 0.76 [0.45, 1.08]. According to benchmark analyses, changes were similar to the magnitude of change in face-to-face CBT and final scores to values of a nonclinical sample. Additionally, similar to findings in face-to-face CBT for panic disorder, longitudinal time analyses revealed that anxiety sensitivity scores predicted later improvement in anxious attachment scores, but not vice versa. Counter to our hypothesis, avoidant attachment did not significantly change during treatment, d = 0.15 [0.02, 0.46]; however, pretreatment level of avoidant attachment in ICBT was similar to the nonclinical sample. Also counter to our hypotheses, agoraphobic avoidant behaviors when alone did not predict changes in anxious attachment. These results suggest that anxious attachment can improve in ICBT for panic disorder even though the focus of the treatment is not on interpersonal relationships. These changes appear to follow changes in anxiety sensitivity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Forensic Mental Health Care Staff Experiences of Providing Palliative Care: A Qualitative Descriptive Case Study Approach.
There is a steady increase in the number of people dying within the walls of forensic institutions across the world. This escalation is, to a large extent, because of an aging population. There is a need to explore how palliative care can be delivered in these settings where, historically, security has been the main focus. The aims of this study were to explore staff experiences of providing palliative care in a forensic mental health unit and to establish the subjective significance of those experiences. A qualitative, descriptive, case study approach was used. This study examined staff perspectives of provision of palliative care to a long-term service user who had been diagnosed with a life-limiting illness and who subsequently died. Interviews were analyzed using codebook thematic analysis. There were nine in-depth interviews with staff who were involved in the service user's care. Analysis resulted in five main themes: intrinsic dignity, "It was out of our depth," "It's just the way these places are," "Hospital was the practical place," and specialist services. If equitable access to palliative care is a human right, then it is essential that individuals in secure care with mental illness are able to access palliative care services that are responsive to their needs. Forensic mental health services need to be proactively prepared for the inevitability that people will die in their care.


Extracorporeal shock wave promotes growth and differentiation of bone-marrow stromal cells towards osteoprogenitors associated with induction of TGF-beta1.
Extracorporeal shock-wave (ESW) treatment has been shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm2 in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O). We found that the mean value for the CFU-O colonies after treatment with 500 impulses of ESW was 168.2 CFU-O/well (SEM 11.3) compared with 88.2 CFU-O/well (SEM 7.2) in the control group. By contrast, ESW treatment did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with 250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses also enhanced the activity of bone alkaline phosphatase in the subculture of CFU-O (p<0.01), indicating a selective promotion of growth of osteoprogenitor cells. Similarly, formation of bone nodules in the long-term culture of bone-marrow osteoprogenitor cells was also significantly enhanced by ESW treatment with 500 impulses. The mean production of TGF-beta1 was 610 pg/ml (SEM 84.6) in culture supernatants from ESW-treated rats compared with 283 pg/ml (SEM 36.8) in the control group. Our findings suggest that optimal treatment with ESW could enhance rat bone-marrow stromal growth and differentiation towards osteoprogenitors presumably by induction of TGF-beta1.


The small molecule that packs a punch: ubiquitin-mediated regulation of RIPK1/FADD/caspase-8 complexes.
The mechanisms that underpin the production of small molecules and cytokines that lead to inflammation or programmed cell death are intricately intertwined. So much so that some of the proteins that contribute to the transcriptional up regulation of cytokines can switch their role in the right circumstances to generate cell death-inducing complexes. This entwinement is reflected in the fact that inflammation helps an organism fight pathogens and that therefore pathogens are under an evolutionary pressure to interfere with this process. Cell death is therefore a defensive measure that may serve to deny pathogens a host cell, expose pathogens to the immune system and also provide additional inflammatory information to the host. Clearly such a system must be tightly regulated and ubiquitylation is a post-translational protein modification that is at the heart of this regulation. In this review, we discuss the regulatory ubiquitin events that dictate the formation and activation of death-inducing complexes containing RIPK1/FADD/caspase-8, and examine how these events collectively determine cell fate.


Usher syndrome: molecular links of pathogenesis, proteins and pathways.
Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear and in photoreceptor cells of the retina. The localization of the Usher proteins and the phenotype in animal models indicate that the Usher protein complex is essential in the morphogenesis of the stereocilia bundle in hair cells and in the calycal processes of photoreceptor cells. In addition, the Usher proteins are important in the synaptic processes of both cell types. The association of other proteins with the complex indicates functional links to a number of basic cell-biological processes. Prominently present is the connection to the dynamics of the actin cytoskeleton, involved in cellular morphology, cell polarity and cell-cell interactions. The Usher protein complex can also be linked to the cadherins/catenins in the adherens junction-associated protein complexes, suggesting a role in cell polarity and tissue organization. A third link can be established to the integrin transmembrane signaling network. The Usher interactome, as outlined in this review, participates in pathways common in inner ear and retina that are disrupted in the Usher syndrome.


Repeat prescribing of medications: A system-centred risk management model for primary care organisations.
Reducing preventable harm from repeat medication prescriptions is a patient safety priority worldwide. In the United Kingdom, repeat prescriptions items issued has doubled in the last 20 years from 5.8 to 13.3 items per patient per annum. This has significant resource implications and consequences for avoidable patient harms. Consequently, we aimed to test a risk management model to identify, measure, and reduce repeat prescribing system risks in primary care. All 48 general medical practices in National Health Service (NHS) Lambeth Clinical Commissioning Group (an inner city area of south London in England) were recruited. Multiple interventions were implemented, including educational workshops, a web-based risk monitoring system, and external reviews of repeat prescribing system risks by clinicians. Data were collected via documentation reviews and interviews and subject to basic thematic and descriptive statistical analyses. Across the 48 participating general practices, 62 unique repeat prescribing risks were identified on 505 occasions (eg, practices frequently experiencing difficulty interpreting medication changes on hospital discharge summaries), equating to a mean of 8.1 risks per practice (range: 1-33; SD = 7.13). Seven hundred sixty-seven system improvement actions were recommended across 96 categories (eg, alerting hospitals to illegible writing and delays with discharge summaries) with a mean of 15.6 actions per practice (range: 0-34; SD = 8.0). The risk management model tested uncovered important safety concerns and facilitated the development and communication of related improvement recommendations. System-wide information on hazardous repeat prescribing and how this could be mitigated is very limited. The approach reported may have potential to close this gap and improve the reliability of general practice systems and patient safety, which should be of high interest to primary care organisations internationally.


Hormonally mediated inheritance of acquired characteristics in Mongolian gerbils.
The intrauterine position relative to members of the same or opposite sex that a rodent fetus occupies affects both its morphology and behaviour when adult. Female fetuses that mature between males are androgenized by testosterone crossing fetal membranes, and their phenotypes as adults differ significantly from those of sisters that received less intrauterine exposure to exogenous testosterone. We report here that adult female Mongolian gerbils that gestated between male fetuses produce litters containing a significantly greater proportion of sons than the litters produced by those that gestated between female fetuses. Consequently, daughters delivered by dams that gestated between male fetuses are more likely to have gestated between male fetuses and be androgenized in utero than are daughters of dams that gestated between female fetuses. Female gerbils thus tend to inherit the phenotype (either androgenized or not androgenized) of their respective mothers.


Epidemiologic characteristics of anotia and microtia in California, 1989-1997.
There is a paucity of epidemiologic information about the external ear malformations anotia and microtia. Using data from a large population-based registry, we explored prevalences and maternal/infant characteristics associated with anotia and microtia. Data were derived from the California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with congenital malformations using multiple source ascertainment. Approximately 2.5 million births (live-born and stillborn) occurred during the ascertainment period, 1989-1997. Information on maternal and infant/fetal characteristics was obtained from California birth certificate and fetal death files. The prevalence of anotia/microtia was 2.50 per 10,000 live births and stillbirths. Isolated cases, i.e., those live births and stillbirths with no other accompanying anomaly diagnoses, revealed a prevalence of 0.63 per 10,000, whereas among nonisolated cases, the prevalence was 1.53 per 10,000 live births and stillbirths. Prevalences of isolated anotia/microtia were substantially higher among U.S.-born Hispanics, foreign-born Hispanics, and Asians compared to non-Hispanic whites, with relative risks ranging from three- to seven-fold. Similar prevalences for maternal race/ethnicity (except for Asians) were observed for live births and stillbirths with nonisolated cases of anotia/microtia, but the magnitude of risks were lower than those observed for isolated cases. Prevalence of nonisolated anotia/microtia was substantially lower among women whose education was 12 years or more. These data reveal descriptive epidemiologic features of anotia/microtia most notably substantial risks associated with race/ethnic groups and lower maternal education. Additional study for factors associated with these characteristics could reveal clues for the etiology of these ear anomalies.


Experience of treatment in the Amanita phalloides poisoning (clinical and experimental observations).
Intensive care was applied in 13 patients with acute liver insufficiency and different degrees of metabolic encephalopathy due to the ingestion of Amanita phalloides. Twelve of them were subjected to hepatic assist with E.T., in three cases this measure was repeated. Ten recoveries were obtained, which denote, on the basis of the necrosis enzymes and the hepatic histo-pathological aspects from bioptic samplings, the use of the E.T. method, when applied within the first 72 hours. In pigs poisoned with Amanita phalloides, the clinico-biochemical pattern and the histopathological findings are comparable to the observations in man. Electron microscopy demonstrates peculiar lesion in the cytoplasm. The anatomo-pathological findings in the three dead patients show a liver necrosis over the 90% and the presence of cerebral edema.


The use of targeted mouse models for preclinical testing of novel cancer therapeutics.
The use of genetically engineered cancer-prone mice as relevant surrogates for patients during the development of pertinent clinical applications is an unproven expectation that awaits direct demonstration. Despite the generally disappointing findings using tumor xenografts and certain early transgenic cancer models to predict therapeutic efficacy in patients, the dramatic progress of mouse models in recent years engenders optimism that the newest generation of mouse models will provide a higher standard of predictive utility in the process of drug development.


Hydroxylation of progesterone by some Trichoderma species.
Thirty-three isolates belonging to six species of the genus Trichoderma were tested for the ability to hydroxylate progesterone to 11alpha-, 11beta-, 11alpha,17alpha- and 6beta, 17alpha-derivatives, and epicortisol. T. aureoviride, T. harzianum, T. polysporum and T. pseudokoningii produced 11alpha-hydroxyprogesterone. T. harzianum and T. hamatum can form only the 11beta-isomer. T. koningii and T. hamatum produced 11alpha-, 11beta-, 11alpha,17alpha- and 6beta,11alpha-hydroxy derivatives. 11alpha, 11beta, 6beta,11alpha- and 11alpha,17alpha-hydroxyprogesterones and epicortisol are produced by T. aureoviride and T. pseudokoningii. Cortisol was produced only when the medium was fortified by 10 g/L peptone. This is the first record of conversion of progesterone to mono-, di- and trihydroxyprogesterones by these Trichoderma species.


Substance use and sexual behaviour among female students in Nigerian universities.
Substance use continues to constitute social and health problems, more so among adolescents and young adults. One consequence is risky sexual behavior, a major problem in sub-Saharan Africa already facing the synergistic problems of poverty and HIV/AIDS. This study of female students aged ≥ 18 years in two universities in Nigeria uses a multi-stage stratified random sampling method, and each subject that gave consent to the study was administered with a structured questionnaire by trained interviewers; 2,408 female students were studied (1,854 from the University of Ibadan and 554 from the Bayero University, Kano). The mean age of the respondents was 21.6 (SD = 2.9), and about two-thirds (65.7%) were aged between 20-24, with 2,204 (91.5%) being single and 4.3% married. In all, 23.4% of the subjects used one form of substance. Alcoholic drinks of palm wine, alcoholic wine, and beer were the most common of substances used (22.7%), followed by tobacco (2%) and cannabis (1%). Substance use was significantly associated with religious affiliation of the students (p < 0.001), as the prevalence of substance use was least among Muslim students (11.7%) and highest among those who professed traditional religion (39.4%). Alcohol use was also positively associated with sexual activity (p < 0.001). Among the 547 students who used alcohol, 147 (26.9%) had sex in the 4 weeks prior to the survey, while among the 1,861 non-users, only 8.9% did so. The practice of unprotected sex was found not to be associated with substance use: a slightly lower proportion (29.5% vs. 36.6%) of substance users engaged in unprotected sex in their last encounter compared to non-users. There is need to scale up public health education on the dangers of substance use and its associated sexual risk behavior.


Quantitative characterization of edge enhancement in phase contrast x-ray imaging.
The aim of this study was to model the edge enhancement effect in in-line holography phase contrast imaging. A simple analytical approach was used to quantify refraction and interference contrasts in terms of beam energy and imaging geometry. The model was applied to predict the peak intensity and frequency of the edge enhancement for images of cylindrical fibers. The calculations were compared with measurements, and the relationship between the spatial resolution of the detector and the amplitude of the phase contrast signal was investigated. Calculations using the analytical model were in good agreement with experimental results for nylon, aluminum and copper wires of 50 to 240 microm diameter, and with numerical simulations based on Fresnel-Kirchhoff theory. A relationship between the defocusing distance and the pixel size of the image detector was established. This analytical model is a useful tool for optimizing imaging parameters in phase contrast in-line holography, including defocusing distance, detector resolution and beam energy.


Nicolau syndrome following intramuscular injection of oxytocin in pregnant women: report of two cases.
Nicolau syndrome, also known as embolia cutis medicamentosa, is a well known but very rare complication occuring after intramuscular drug injections and presenting with local intense pain. Immediately after injection the skin blanches and within minutes to hours an erythematous macule develops, which evolves into a livedoid violaceous patch with dendrites. This condition is initially hemorrhagic, then it ulcerates, and eventually heals with an atrophic scar. Many different drugs have been reported to cause Nicolau syndrome . To date there have been no reports of Nicolau syndrome caused by intramuscular oxytocin injection. We would like to report two cases that occured after intramuscular injection of oxytocin.


Metastasis of renal cell carcinoma to the contralateral renal pelvis.
Extremely rarely renal cell carcinoma metastasizes to the contralateral renal pelvis or ureter. The present report concerns a case where a metastatic tumor could be successfully removed from the left renal pelvis 3 years after right nephrectomy for the primary tumor. A review of the literature revealed this to be only the fourth such case documented.


Patient-reported outcome during radiotherapy for head and neck cancer: the use of different PRO questionnaires.
Head and neck cancer (HNC) patients are typically treated with radiotherapy (RT), which might lead to side effects and deterioration of quality of life (QoL). Studies in other cancers indicate that systematic use of patient-reported outcome (PRO) can be a tool to increase awareness of patients' symptoms and improve QoL. Multiple PRO questionnaires have been developed and validated for HNC, complicating the interpretation of results from scientific studies. In this exploratory study, symptom scores from four essential symptoms present in four different HNC-specific PRO questionnaires were evaluated. Four HNC-specific PRO questionnaires (EORTC QLQ-H&N35, FACT-H&N, MDASI-HN, and PRO-CTCAE) for patients undergoing radiotherapy were completed by eligible HNC patients up to ten times during and after RT. Four essential symptoms (pain, dysphagia, hoarseness, and dry mouth) were present in all questionnaires. The symptom scores for these symptoms were aligned and evaluated. Twelve patients were included and completed a total of 328 PRO questionnaires out of 420. Similarity between symptom score for the four symptoms was found, when the symptom scores were aligned. The symptom scores increased during RT and decreased afterwards for all four symptoms and in all four questionnaires. Four HNC-specific PRO questionnaires are found similar in reflecting symptom scores over time concerning four important HNC symptoms (pain, dysphagia, hoarseness, and dry mouth). PRO can contribute with targetable information about symptoms, and PRO questionnaires might be a valuable add on to clinical practice enabling a varied picture of patients' symptoms during radiotherapy.


Unique sequence specificity of topoisomerase II DNA cleavage stimulation and DNA binding mode of streptonigrin.
Streptonigrin stimulated unique intensity patterns of topoisomerase II-mediated DNA cleavage in agarose and sequencing gels with no similarity to those of doxorubicin, VM-26,4'(9-acridinylamino)-methanesulfon-m-anisidide, genistein, and mitoxantrone. Surprisingly, a statistical analysis of 60 sites stimulated by streptonigrin in SV40 and pBR322 DNAs showed that the drug required the dinucleotide 5'-TA-3' from 2- to 3-positions at the DNA cleavage site. Streptonigrin did not intercalate into the double helix; however, a positive value of the reduced linear dichroism indicated that indeed the drug interacted with the DNA. An angle of 45 degrees was found between the major drug and local DNA axes, suggesting a minor groove binding mode. Moreover, a DNA winding assay showed that streptonigrin may tighten the helical twist of DNA, similar to the known minor groove binder distamycin. Drug competition for receptor site binding was then evaluated by drug combination in the cleavage reaction. DNA cleavage intensity patterns were altered only with the streptonigrin/mitoxantrone combination, suggesting that the two compounds may compete for ternary complex formation. The results indicate that streptonigrin may bind to the DNA in a manner similar to that of minor groove binders and that its pharmacophore, possibly different from other topoisomerase II inhibitors, may be an important determinant of its unique sequence position specificity.


Dual-energy CT for differentiating acute intracranial hemorrhage from contrast staining or calcification: a meta-analysis.
This study aimed to comprehensively evaluate the diagnostic performance of dual-energy CT (DECT) for differentiating acute intracranial hemorrhage (ICH) from contrast staining or small calcifications via a systematic review and meta-analysis. The PubMed-MEDLINE, EMBASE, and Cochrane Library databases were searched up to November 10, 2019. Original studies (prospective or retrospective cohort studies) with the primary aim of detecting ICH using DECT were selected. The diagnostic performance of DECT was assessed using bivariate and hierarchical summary receiver operating characteristic models. Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies-2, while between-study heterogeneity was assessed using Higgins' inconsistency index (I2). To explore heterogeneity, subgroup meta-regression analyses were performed. Deeks' funnel plot asymmetry test was used for assessing publication bias. Nine studies comprising 402 patients with 453 lesions were included for data synthesis. The overall pooled sensitivity and specificity of DECT for ICH detection were 96% (95% CI, 77-99%) and 98% (95 CI, 93%-100%), respectively. Substantial and moderate between-study heterogeneities were observed for sensitivity (I2 = 90.3%) and specificity (I2 = 57.9%), respectively. In meta-regression analysis, type of cohort affected heterogeneity-studies including only stroke patients showed lower sensitivity (43.5% vs. 94.2%) but higher specificity (98.7% vs. 92.6%) than those with mixed etiologies (P < 0.001). Deeks' funnel plot asymmetry test revealed publication bias (P = 0.020). DECT demonstrated excellent diagnostic performance in terms of differentiating acute ICH from contrast staining and small calcifications. However, publication bias suggests the possibility of overestimated diagnostic performance, warranting large-scale, prospective cohort studies.


Simple and rapid determination of homozygous transgenic mice via in vivo fluorescence imaging.
Setting up breeding programs for transgenic mouse strains require to distinguish homozygous from the heterozygous transgenic animals. The combinational use of the fluorescence reporter transgene and small animal in-vivo imaging system might allow us to rapidly and visually determine the transgenic mice homozygous for transgene(s) by the in vivo fluorescence imaging. RLG, RCLG or Rm17LG transgenic mice ubiquitously express red fluorescent protein (RFP). To identify homozygous RLG transgenic mice, whole-body fluorescence imaging for all of newborn F2-generation littermates produced by mating of RFP-positive heterozygous transgenic mice (F1-generation) derived from the same transgenic founder was performed. Subsequently, the immediate data analysis of the in vivo fluorescence imaging was carried out, which greatly facilitated us to rapidly and readily distinguish RLG transgenic individual(s) with strong fluorescence from the rest of F2-generation littermates, followed by further determining this/these RLG individual(s) showing strong fluorescence to be homozygous, as strongly confirmed by mouse mating. Additionally, homozygous RCLG or Rm17LG transgenic mice were also rapidly and precisely distinguished by the above-mentioned optical approach. This approach allowed us within the shortest time period to obtain 10, 8 and 2 transgenic mice homozygous for RLG, RCLG and Rm17LG transgene, respectively, as verified by mouse mating, indicating the practicality and reliability of this optical method. Taken together, our findings fully demonstrate that the in vivo fluorescence imaging offers a visual, rapid and reliable alternative method to the traditional approaches (i.e., mouse mating and real-time quantitative PCR) in identifying homozygous transgenic mice harboring fluorescence reporter transgene under the control of a ubiquitous promoter in the situation mentioned in this study.


A novel general route for the synthesis of C-glycosyl tyrosine analogues.
A general method for the synthesis of C-glycosyl amino acids is described here. The stereoisomerically pure tyrosine analogues alpha-L-4 and beta-L-6 are prepared in reasonable overall yields from allyl derivatives 10 and 11. The key step is a benzannulation procedure which is employed in the creation of the aromatic ring that bears the amino acid function.


Orthodontic and surgical management of a patient with severe skeletal Class II deformity and facial asymmetry: A case report with a 5-year follow-up.
In this case report, we present the orthodontic and surgical management of an 18-year-old girl who had a severe craniofacial deformity, including maxillary prognathism, vertical maxillary excess (gummy smile), mandibular retrognathism, receding chin, and facial asymmetry caused by unilateral temporomandibular joint ankylosis. For correction of the facial asymmetry, the patient's right mandibular ramus and body were lengthened via distraction osteogenesis after 5 months of preoperative orthodontic therapy. Subsequently, extraction of 4 first premolars, bimaxillary anterior segmental osteotomy, and genioplasty were simultaneously performed in the second-stage operation to correct the skeletal deformities in the sagittal and vertical planes. Postoperative orthodontic treatment completed the final occlusal adjustment. The total active treatment period lasted approximately 30 months. The clinical results show that the patient's facial esthetics were significantly improved with minimal surgical invasion and distress, and a desirable occlusion was achieved. These pleasing results were maintained during the 5-year follow-up.


Comparative Neuropeptidomic Analysis of Food Intake via a Multi-faceted Mass Spectrometric Approach.
Feeding behavior is a fundamental aspect of energy homeostasis and is crucial for animal survival. This process is regulated by a multitude of neurotransmitters including neuropeptides within a complex neuroendocrine system. Given the high chemical complexity and wide distribution of neuropeptides, the precise molecular mechanisms at the cellular and network levels remain elusive. Here we report comparative neuropeptidomic analysis of brain and major neuroendocrine organ in a crustacean model organism in response to feeding. A multi-faceted approach employing direct tissue matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), stable isotopic labeling of neuropeptide extracts for quantitation, and mass spectrometric imaging (MSI) has been employed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and the pericardial organ (PO) in the crab Cancer borealis. Multiple neuropeptides exhibited changes in abundance after feeding, including RFamides, Cancer borealis tachykinin related peptides (CabTRPs), RYamides, and pyrokinins. By combining quantitative analysis of neuropeptide changes via isotopic labeling of brain extract and MSI mapping of neuropeptides of brain slices, we identified the boundary of olfactory lobe (ON) and median protocerebrum (MPC) area as two potential feeding centers in the crab brain.


Enhanced pulmonary alpha-2 adrenoceptor responsiveness under conditions of elevated pulmonary vascular tone.
Alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog under conditions of normal and elevated pulmonary vascular tone. Under conditions of normal pulmonary vascular tone (10 +/- 1 mm Hg), methoxamine, a selective alpha-1 adrenoceptor agonist, and B-HT 933, a selective alpha-2 adrenoceptor agonist, elicited maximal increases in lobar perfusion pressure of 5 and 2 mm Hg above resting pulmonary tone, respectively. When pulmonary vascular tone was elevated progressively with the thromboxane mimetic, U-46619, serotonin or PGF2 alpha, alpha-1 adrenoceptor-mediated pulmonary vasoconstrictor responses to methoxamine were unaffected, whereas alpha-2 adrenoceptor-mediated pulmonary pressor responses to B-HT 933 were enhanced. Overall the response to B-HT 933 was enhanced 4-fold when pulmonary perfusion pressure was elevated to 19.8 +/- 0.8 mm Hg with U-46619 and almost 5-fold when elevated to 27.0 +/- 1.2 mm Hg. Pulmonary vasoconstrictor responses to angiotensin II were unaffected by elevated pulmonary vascular tone. Enhanced responsiveness of B-HT 933 to elevated pulmonary vascular tone was antagonized by the selective alpha-2 adrenoceptor antagonist, rauwolscine (100 micrograms/kg i.v.), and unaffected by the selective alpha-1 adrenoceptor antagonist, prazosin (100 micrograms/kg i.v.). When canine intralobar pulmonary veins were studied in vitro they contracted to B-HT 933 whereas intralobar pulmonary arteries did not respond. These data indicate that alpha-2 adrenoceptor responsiveness is enhanced markedly and selectively under conditions in which pulmonary vascular tone is elevated.


Two new deep-water species of the genus Thorogobius (Teleostei: Gobiidae) from the upper continental slope of the Eastern Central Atlantic.
Two new gobiid species, Thorogobius alvheimi sp. nov. and Thorogobius laureatus sp. nov. (Teleostei: Gobiiformes: Gobiidae), are described from the outer continental shelf and upper slope of the Eastern Central Atlantic off Angola, Ghana and São Tomé and Príncipe. The specimens were trawled from depths between 57 and 208 m. The new species are most similar to Thorogobius angolensis. Thorogobius alvheimi sp. nov. is distinguished from its congeners in the combination of following characters. Fins: first dorsal fin with the second and third spines distinctly elongated; pectoral fin ray count 20-21; pelvic disc complete and short with well-developed anterior membrane (frenum) and pointed lateral lobes. Scales: nape and predorsal area naked; no scales on opercle; scales in longitudinal series 27-31. Pattern of free neuromasts: supratemporal rows tr and trp developed, extending transversally between pores H and K; longitudinal row g short, not passing row m posteriorly and distinctly distant from row h; infraorbital row 6 long, ventrally extending to lower margin of preopercle, its ventral section 6i originating anterior to its dorsal section 6s; posterior lateral row h reaching anteriorly above posterior third of opercle. Coloration: body uniformly pale fawn and brown; margin of scale pockets dark brown pigmented, yielding a reticulated pattern; pale spots on nape and predorsal area; caudal fin uniformly dusky greyish. Thorogobius laureatus sp. nov. is distinguished from its congeners in the combination of following characters. Fins: first dorsal fin the second and third spines distinctly elongated; pectoral fin ray count 19-22; pelvic disc complete, short, with well-developed anterior membrane (frenum) with pointed lateral lobes. Scales: scales on sides of predorsal area and midline mostly naked; no scales on opercle; scales in longitudinal series 24-27. Pattern of free neuromasts (sensory papillae): supratemporal rows tr and trp developed, extending transversally between pores H and K; longitudinal row g long, passing row m posteriorly and relatively close to row h; infraorbital row 6 long, ventrally extending to lower margin of preopercle, its ventral (6i) and dorsal (6s) originating opposite to each other; posterior lateral rows: row h long, reaching anteriorly above middle of opercle. Coloration: body pale fawn and brownish; margin of scale pockets dark brown pigmented, yielding a reticulated pattern; five brown blotches on flanks in lateral midline from below first dorsal fin to caudal peduncle; caudal fin with six or seven distinct dark vertical bands.


The antimetastatic function of concomitant antitumor immunity. I. Host Ly-1+2+ effector T cells prevent the enumeration of metastatic tumor cells in a biological assay.
A mouse survival assay was evaluated for its suitability to enumerate metastatic P815 tumor cells in the draining lymph node and spleen of a B6D2 F1 (H-2b X H-2d) host bearing a primary intradermal P815 tumor. The mouse survival assay is based on the linear relationship between the log10 number of P815 tumor cells (H-2d) injected i.p. into mice and their mean survival time. It was found that the assay is capable of quantifying as few as 10 tumor cells in lymph node and spleen, but only if cell suspensions of these organs are treated with anti-H-2b serum and complement, in order to selectively destroy H-2bd host cells. This was necessary because host cells from the lymph node and spleen of a tumor-bearing host possessed antitumor functions, in that they were capable of destroying the H-2d P815 tumor cells when admixed with the tumor cells and injected i.p. into 800-rad irradiated test recipients. The kinetics of acquisition and loss of host cells with antitumor function and the Ly phenotype of these host cells suggest that they are the same cells that give the tumor-bearing host the capacity to express concomitant immunity against a tumor implant.


Eye movement patterns and visual attention during scene viewing in 3- to 12-month-olds.
Recently, two attentional modes have been associated with specific eye movement patterns during scene processing. Ambient mode, characterized by short fixations and long saccades during early scene inspection, is associated with localization of objects. Focal mode, characterized by longer fixations, is associated with more detailed object feature processing during later inspection phase. The aim of the present study was to investigate the development of these attentional modes. More specifically, we examined whether indications of ambient and focal attention modes are similar in infants and adults. Therefore, we measured eye movements in 3- to 12-months-old infants while exploring visual scenes. Our results show that both adults and 12-month-olds had shorter fixation durations within the first 1.5 s of scene viewing compared with later time phases (>2.5 s); indicating that there was a transition from ambient to focal processing during image inspection. In younger infants, fixation durations between two viewing phases did not differ. Our results suggest that at the end of the first year of life, infants have developed an adult-like scene viewing behavior. The evidence for the existence of distinct attentional processing mechanisms during early infancy furthermore underlines the importance of the concept of the two modes.


Long-Term Cyclability of Electrochromic Poly(3-hexyl thiophene) Films Modified by Surfactant-Assisted Graphene Oxide Layers.
Organic electrochromic (EC) materials are generally known to be electrochemically unstable during the ion intercalation/deintercalation process. One effective method to stabilize them is incorporating graphene derivatives in the polymer matrix, thereby creating strong interaction between graphene derivatives and polymer. However, previous studies are limited to specific polymers and bulk-blended systems, such as mixing the polymer with graphene derivatives. In this study, we developed a polymer-graphene derivative complex with the chemical assistance of a surfactant (octadecylamine, ODA). Graphene oxide (GO) was introduced as a protective layer on the electrochromic poly(3-hexyl thiophene) (P3HT) films by the Langmuir-Schaefer method. The deposition of the GO-ODA protective layer with high coverage was confirmed by atomic force microscopy and high-resolution X-ray reflectivity. The strong interactions between GO-ODA and P3HT were examined with UV-vis spectrophotometry and X-ray photoelectron spectroscopy. Electrochemical and electrochromic investigations revealed that the GO-ODA layer greatly improved the long-term cyclability of the P3HT film. These findings imply that the GO-ODA complex can significantly stabilize the EC cycling, due to its strong interaction with the P3HT film.


Growth and failure to thrive.
Monitoring of growth in early life is particularly important as growth is elastic and sensitive to environmental factors, especially nutrition. Deficits are unlikely to be recovered fully in a later period and early growth patterns contribute to many diseases of adulthood. Assessment of rate of growth, rather than attained size, is possible with today's charts and accurate measurement. Growth monitoring is important for recognition of failure to thrive and it is valuable as a proxy measure for wellbeing. Many factors can contribute to failure to thrive which is best managed using a multidisciplinary approach.


Substance use patterns and in-hospital care of adolescents and young adults attending music concerts.
Few studies describe medical complaints and substance use patterns related to attending music concerts. As such, the objective of this study is to describe patient demographics, substance use and intoxication patterns, and medical interventions provided to adolescents and young adults assessed in an emergency department (ED) for complaints directly related to concert attendance. A retrospective chart review of patients 13-30 years old who were transported to the ED directly from music concerts between January 2011 and December 2015 was conducted. Descriptive statistics and logistic regression were used to analyze patient demographic, intervention, and substance use data. There were 115 concerts identified, of which 48 (42%) were linked to 142 relevant ED visits; the total number of attendees at each concert is unknown. The mean age of the 142 described patients was 19.5 years (SD 3.3) with 72% < 21 and 33% < 18; 71% of patients were female and 96% of visits were substance-use related. Mean blood alcohol level was 242 mg/dL (range 104-412, SD 70). Glasgow Coma Scale (GCS) scores ranged from 3 to 15, with a mean of 14. Two patients required intubation and 61% of patients received interventions, including medications (47%), intravenous fluids (46%), specialty consultation (20%), restraints (14%), imaging (6%), and laceration repair (3%). Attendance at pop and electronic dance music concerts was associated with the widest ranges of GCS scores (8-15 and 6-14 respectively), mass casualty incident declarations, and among the highest mean blood alcohol levels (246 and 244 mg/dL, respectively). Substance use is the predominant reason for music concert related ED visits and patients may have serious levels of intoxication, receiving multiple medical interventions. These data demonstrate the need for additional large-scale studies to confirm trends and increase awareness of this important public health problem.


In vitro evaluation of tigecycline and comparative agents in 3049 clinical isolates: 2001 to 2002.
Tigecycline is the first glycylcycline antimicrobial in phase III clinical trials. This study compares the in vitro activity of tigecycline to 12 other predominately broad-spectrum antimicrobials against 3049 recent inpatient isolates from 38 clinical centers in 17 countries. The minimum concentration at which tigecycline inhibited 90% of the isolates for the entire collection, excluding Pseudomonas aeruginosa, was 1 microg/mL, including vancomycin-resistant enterococci-, extended-spectrum beta-lactamase-, and methicillin-resistant Staphylococcus aureus-resistant phenotypes.


A possible role for L-selectin in the release of polymorphonuclear leukocytes from bone marrow.
Previous studies from our laboratory have shown that the expression of L-selectin on polymorphonuclear leukocytes (PMN) is higher in the bone marrow than in peripheral blood. The present study was designed to determine the location of this L-selectin loss as the PMN pass from the hematopoietic tissue into venous sinusoids of the bone marrow. Bone marrow and peripheral blood samples were collected at the beginning, during, and just after five normothermic cardiopulmonary bypass procedures in which there was active marrow release and compared with five hypothermic procedures in which marrow release was suppressed by lowering body temperature to 27 degrees C. L-selectin expression was measured on PMN in the hematopoietic tissue and venous sinusoids in the bone marrow using quantitative histology and immunocytochemistry. At baseline there was more L-selectin on PMN in the bone marrow hematopoietic tissue than in the sinusoids (24.7 +/- 3.5 vs. 10.3 +/- 2.5%, P < 0.004). Bone marrow release during normothermic cardiopulmonary bypass procedure was associated with a rise in peripheral blood band cells (0.18 +/- 0.7 vs. 2.98 +/- 0.56 x 10(9)/l, P < 0.01) and a further reduction of L-selectin expression on PMN in the sinusoids (P < 0.03). Hypothermia (27 degrees C) prevented both the rise in peripheral blood band cells and the reduction in L-selectin on PMN in the sinusoids. In vitro studies showed that lowering the temperature had a similar effect on shedding of L-selectin from PMN. We conclude that PMN shed L-selectin as they move from the hematopoietic compartment into the venous sinusoids of the bone marrow and postulate that this could control the release of PMN from the marrow.


Viral shedding and emission of airborne infectious bursal disease virus from a broiler room.
1. The significance of airborne transmission in epidemics of infectious diseases in the livestock production industry remains unclear. The study therefore investigated the shedding route (faeces vs. exhaled air) of a vaccine strain of infectious bursal disease virus (IBDV) by broilers and the emission of airborne virus. 2. The experimental room contained 526 broilers which were orally inoculated at the age of 20 d. The airborne virus was sampled by three different bioaerosol samplers: Andersen six-stage impactor, all-glass impinger (AGI-30) and OMNI-3000. 3. Infected broilers started to shed virus in faeces on d 5 post inoculation (PI), and stopped shedding on d 12 PI. The faecal virus remained detectable for at least two d after drying under broiler room conditions. No virus was detected in the air exhaled by broilers. 4. Airborne virus was collected on d 5, 8 and 12 PI at 20 cm above the floor, and on d 8 and 12 PI in exhausted air. The emission rates of IBDV were 4·0 log10 50% tissue culture infectious dose (TCID50)/bird/d on d 8 PI, and 4·5 log10 TCID50/bird/d on d 12 PI. 5. We concluded that broilers shed IBDV mainly through their faeces. The presence of indoor airborne virus is associated with the viral presence in faeces. The successful recovery of airborne virus in exhausted air indicates there is a potential risk of virus spreading to the ambient environment via air.


Atomic and molecular intracules for excited states.
Intracules in position space, momentum space and phase space have been calculated for low-lying excited states of the He atom, Be atom, formaldehyde and butadiene. The phase-space intracules (Wigner intracules) provide significantly more information than the position- and momentum-space intracules, particularly for the Be atom. Exchange effects are investigated through the differences between corresponding singlet and triplet states.


D- and L-β-Hydroxybutyrate Dehydrogenases and the Evolution of Ketone Body Metabolism in Gastropod Molluscs.
In vertebrate animals, ketone bodies, synthesized primarily from stored lipid, are important metabolic substrates (1). During starvation, ketone bodies, acetoacetate (Acac) and {beta}-hydroxybutyrate (BHB), are oxidized by some extrahepatic tissues at high rates, and thus perform the important function of sparing limited glycogen stores (1, 2). The enzyme {beta}-hydroxybutyrate dehydrogenase (BHBDH), which catalyzes the interconversion of the ketone bodies, is found in all mammals and most vertebrates, but is absent in most invertebrates (1, 3), including marine molluscs (4). The highest measured BHBDH activities in the animal kingdom, however, are found in the hearts of terrestrial gastropod molluscs (5, 6). We have recently demonstrated that, in tissues of the terrestrial gastropod Cepaea nemoralis, two unique and previously unknown isoforms of BHBDH occur (5). The isoforms differ from the well-characterized mitochondrial membrane-bound D-BHBDH found in all other animals (7) in that they are cytosolic, and one isoform is specific for the L-enantiomer of BHB. Here we identify patterns in the evolution of these enzyme isoforms in the Gastropoda. BHBDH activities, stereospecificity and subcellular compartmentalization were measured in gastropod species representing four major groups with freshwater and terrestrial representation: Neritomorpha (primitive gilled gastropods), Architaenioglossa (more advanced gilled gastropods), Basommatophora (freshwater pulmonates), and Stylommatophora (terrestrial pulmonates). Mapping of these data onto a phylogeny of the Gastropoda (8) indicates that cytosolic D- and L-BHBDH have arisen a single time, in an ancestral stylommatophoran. All gastropods of the order Stylommatophora possess this unique organization of ketone body metabolism, which has not been found elsewhere in the animal kingdom.


Excavating abiotic stress-related gene resources of terrestrial macroscopic cyanobacteria for crop genetic engineering: dawn and challenge.
Genetically engineered (GE) crops with resistance to environmental stresses are one of the most important solutions for future food security. Numerous genes associated to plant stress resistance have been identified and characterized. However, the current reality is that only a few transgenic crops expressing prokaryotic genes are successfully applied in field conditions. These few prokaryotic genes include Agrobacterium strain CP4 EPSPS gene, Bacillus thuringiensis Cry1Ab gene and a bacterial chaperonin gene. Thus, the excavation of potentially critical genes still remains an arduous task for crop engineering. Terrestrial macroscopic cyanobacteria, Nostoc commune and Nostoc flagelliforme, which exhibit extreme resistance to desiccation stress, may serve as new prokaryotic bioresources for excavating critical genes. Recently, their marker gene wspA was heterologously expressed in Arabidopsis plant and the transgenics exhibited more flourishing root systems than wild-type plants under osmotic stress condition. In addition, some new genes associated with drought response and adaptation in N. flagelliforme are being uncovered by our ongoing RNA-seq analysis. Although the relevant work about the terrestrial macroscopic cyanobacteria is still underway, we believe that the prospect of excavating their critical genes for application in GE crops is quite optimistic.


[Textual research on the hypothesis of Zhang Zhong-jing "being the governor of Changsha"].
It was always a historical disputed case on the hypothesis of Zhang Zhong-jing, a famous doctor in the Eastern Han Dynasty (25 - 220 A.D.), was once the governor of Changsha. Based on large amount of studies on archival materials combining with unearthed relics, it can be fully ascertained that Zhang Zhongjing had been the governor of Changsha with his tenure in the year of Jian'an 7th to 10th or 12th year, ie, from 202 A.D. to 205 or 207. During this period, Zhang insisted to have clinical practice and wrote his Shang Han Za Bing Lun (Treatise on Exogenous Cold and Miscellaneous Diseases), exerting profound influence on later generations. The Zhang-gong ci (memorial ancestral temple for Mr. Zhang) was built in Changsha city in the Qing dynasty to commemorate him and the medical sage Zhang Zhong-jing is recalled and venerated deeply by the people in the city even today.


The treatment of renovascular hypertension: surgery, angioplasty, and medical therapy with converting-enzyme inhibitors.
Surgery has been used to treat renal vascular hypertension for almost 50 years. The reason for the many apparent discrepancies in the literature on effectiveness and risk have become clear only in the past decade. The results are poorest and the risk is greater, not surprisingly, in patients with advanced atherosclerosis involving many vascular beds. The results are much better in fibromuscular disease, both in terms of effectiveness and risk. Angioplasty has been available for a much shorter time, but a reasonable picture of the short-term effectiveness and the risk is emerging. The risk is substantially lower than that of surgery. The results are again best in fibromuscular disease. In atherosclerotic disease, the results are especially poor for the most common lesion, that involving the renal artery ostium. Medical therapy before the development of captopril was often difficult and often unsatisfactory. Since the development of converting-enzyme inhibition, medical therapy is an important option. In the early experience, reflecting the severity of the hypertension, the frequency with which azotemia was present, and the high dose of captopril used, the adverse reaction rate was substantial. In one study, none of 133 patients with unilateral renal arterial disease and an intact contralateral kidney developed renal failure. Among 136 patients with bilateral disease or a solitary kidney, renal failure occurred in 15 and led to discontinuation of therapy in 12. If surgery or angioplasty are contraindicated, one can modify the therapeutic goal.(ABSTRACT TRUNCATED AT 250 WORDS)


Behavioural reactivation and subjective assessment of the state of vigilance--application to simulated car driving.
The frequency of some behaviour (such as self-centred gestures) increases during a task that leads to the occurrence of low-vigilance episodes. These gestures can be useful in stimulating oneself. A study carried out in 20 adults has enabled us to state that motor activity (recorded with an actimeter) increases with the duration of a monotonous driving task and sleep deprivation. The analysis of the scores recorded using the Karolinska Sleepiness Scale has shown that drivers can assess the deterioration of their state of vigilance according to the actual sleep preceding the driving test. Finally, the joint analysis of the subjective and objective data revealed a co-variation of these two types of indices. We discuss the stimulatory function of the motor activity in a task leading to the occurrence of low-vigilance episodes by investigating, among other things, the use, conscious or not, of this type of activity.


Entamoeba histolytica: antibody response to recent and past invasive events.
Sero-epidemiological data from endemic amoebiasis areas are difficult to evaluate because the serology of individuals affected by an active process of Entamoeba histolytica tissue invasion is, at present, almost impossible to distinguish from that of individuals who have had an invasive event in the past. The present study compares serum antigenic recognition frequencies among three groups of individuals with different infective conditions: amoebic liver abscess patients; asymptomatic cyst passers; and individuals who have had amoebic liver abscess from one to three years before the study. Control groups consisted of Mexican and Canadian healthy adults. Western blots of E. histolytica membrane extract antigen were reacted with sera from the studied individuals, recognition frequency values were calculated and immunoplots of frequency differences were constructed. The results obtained suggest that the identification and purification of antigenic fractions, which are frequently recognized by sera of amoebic liver abscess patients (136, 132, 93, 70 and 62 kDa), or preferentially associated with past invasive events (144, 140 and 49 kDa), or related to the E. histolytica cyst passer condition (62 and 136 kDa), are important improvements in the use of serology for diagnosis and epidemiological studies in endemic areas of amoebiasis.


Parenteral aluminum loading in critical care medicine. Part I: Aluminum content of infusion solutions and solutions for parenteral nutrition.
For patients with disturbed aluminum (Al) excretion, a high Al intake is not without risk. As main aluminum sources infusion solutions and solutions for parenteral nutrition have been identified. This study will give current survey of aluminum loading of the above-mentioned preparations. The aluminum loading of 139 different infusion solutions and solutions for parenteral nutrition was determined. The solutions were from the clinical pharmacy of the Klinikum Steglitz of the Free University Berlin or were bought in a public pharmacy. The aluminum content was determined by means of two different, independent analytical methods: a) graphite furnace atomic absorption spectroscopy (GFAAS) and b) inductively coupled plasma atomic emission spectroscopy (ICP-AES). The agreement of the measured values was good except for five samples, where different values were found. Mistakes due to contamination were excluded on the basis of the results of measuring standard reference materials. Small-volume additives of TPN (total parenteral nutrition) formulations were highly contaminated with aluminum, e.g. Ca and phosphate solutions (29-12,000 micrograms/l), vitamin C solutions (700-1,200 micrograms/l) and trace element solutions (67-6,200 micrograms/l). Furthermore about 44% of the crystalline amino acid solutions and lipid emulsions had an aluminum content of 25 to 55 micrograms/l. Low aluminum levels were found in carbohydrate solutions, NaCl and KCl solutions and in distilled water (aqua ad injectabilia). Many of the solutions for parenteral nutritional support have an aluminum content which exceeds, in part considerably, the suggested threshold concentration of 25 micrograms/l (0.93 mumol/l), recommended by the American Society for Clinical Nutrition (ASCN) and the American Society for Parenteral and Enteral Nutrition (ASPEN). The pharmaceutical industry should be required to check the manufacturing process for avoidable sources of contamination, and threshold values for aluminum loading by intravenously applied pharmaceuticals should be laid down in the German and European pharmacopoeia. In cases where contaminations cannot be eliminated during the manufacturing process after careful checking, the aluminum content of the infusion solution should be declared for the user.


Surface decomposition accompanying the perception of transparency.
At the retina, each location can have only one value of luminance or color. When transparency is perceived, however, different surface qualities can be redistributed to two or more apparently superimposed layers. The experiments described here explored the characteristics of this surface decomposition. It is shown that the surface decomposition occurs rapidly, it affects even early stages of visual processing, and it involves attributes such as texture and motion as well as color and brightness. In the first experiment, the recognition advantage for transparent overlapping digits demonstrated that the surface decomposition accompanying transparency occurs within 60 ms. In the second, the separation of overlying orthogonal grids due to surface decomposition was found to influence the strength of the McCollough effect, an effect attributed to early cortical processing. Finally, when a transparent surface appears to extend over areas that are physically identical to the background, qualities of the transparent overlay such as texture and motion, as well as color or brightness (e.g., the neon color effect) appear to spread to the illusory overlay.


Peridontal status following surgical-orthodontic alignment of impacted teeth.
Treatment of impacted teeth is often a combination between oral surgery and orthodontics. This study evaluates the gingival condition of impacted teeth after surgical-orthodontic treatment, where two different surgical methods were used. In one group (n = 11) the teeth were radically exposed and orthodontically moved to their final position. In the other group (n = 11) the teeth were partially exposed by raising a mucoperiosteal flap. Orthodontic traction was then applied; whereafter the flap was sutured back into place. The results showed that one of the teeth in the partial exposure group and seven in the radical exposure group showed loss of attachment. This study indicates that a combination of mucoperiosteal flap technique and applied orthodontic traction is prefered to minimize the loss of attachment in cases of displaced impacted teeth.


Incidence of cardiac arrhythmias during antidepressant therapy with maprotiline or nomifensine.
In a prospective randomized study we searched for arrhythmogenic effects of the tetracyclic antidepressant, a maprotiline, and the tetrahydroisoquinoline derivative, nomifensine. Forty depressive patients from the psychiatric outpatients department were included in the study. Twenty patients in each group received maprotiline or nomifensine over three weeks in the recommended daily dosage of 75 mg. Rhythm analysis was performed before therapy, at the end of 3 weeks therapy, and 1 week after withdrawal from medication using a dual channel long-term ECG with monitoring periods of 10 h during normal daily activities. Before treatment, spontaneous incidence of all ventricular ectopics and of their complex forms was within the normal range when compared with ectopic activity of 121 "normal subjects" without detectable heart disease. No significant increase could be demonstrated during therapy with maprotiline or nomifensine, nor was any change observed 1 week after medication had been stopped. The same was true for supraventricular extrasystoles; atrial tachycardia, atrial flutter, and fibrillation were never seen. Sinoatrial (n=2) and atrioventricular block (n=1) were rare findings independent of and not affected by treatment. No bundle branch blocks were observed before, during, and after treatment. In contrast, despite the conservative dosage of both drugs, a therapy-dependent increase in average heart rate was found (p less than 0.001). This increase was significantly higher in patients receiving nomifensine than in those treated with maprotiline (p less than 0.001), suggesting a lower intrinsic anticholinergic activity of the latter compound.


Why Do the Fetal Membranes Rupture Early after Fetoscopy? A Review.
Iatrogenic preterm premature rupture of the fetal membranes (iPPROM) remains the Achilles' heel of keyhole fetal surgery (fetoscopy) despite significant efforts in preclinical models to develop new therapies. This limited success is partially due to incomplete understanding why the fetal membranes rupture early after fetoscopy and notable differences in membrane physiology between humans and domestic species. In this review, we summarize aspects of fetoscopy that may contribute to iPPROM, the previous efforts to develop new therapies, and limitations of preclinical models commonly used in fetal membrane research.


Determination of pesticide residues in varieties of pepper sold at different periods and provinces in Turkey and investigation of their adverse effects on human health and the environment.
Pesticides are dangerous chemicals that can harm to people and the environment when applied inappropriately or in excess. In this research, various pesticide residues were investigated in 48 pepper samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). All samples were collected randomly in two periods of time (September and December) from markets and greengrocers in four provinces (Siirt, Mardin, Diyarbakir, and Batman). Considering the means of the first and second periods, diclofop-methyl had the highest concentration of 29.4 ± 7.7 µg kg-1, and diazinon had the lowest of 21.1 ± 4.6 µg kg-1. Based on the maximum residue limits (MRLs) of pesticides specified in the Turkish Food Codex, pyrimethanil, bupirimate, and diclofop-methyl were found to be below the maximum acceptable residue limit, while pyridaphention, dinoseb, diazinon, and pirimiphos-methyl were found to be above the limit. Thus, the current study demonstrated the potential of LC-MS/MS as a crucial technique for accurate measurements and confirmations of pesticides in different pepper varieties.


The effect of age and sex on pelvic bone density measured opportunistically in clinical CT scans.
Unstable pelvic ring fractures are severe and complex injuries, and surgical fixation is challenging and can be complicated by early failure due in part to difficulties with securely fixing screws in low-density bone. There is limited information in the literature about how the density distribution across the pelvic bones changes with age and sex. In this study, we used 60 sets of calibrated bone density measurements obtained opportunistically from clinical computed tomography scans of the pelvis. Three-dimensional models of the innominate bone were produced and the effects of age and sex on cortical bone density modeled. Overall trends and regions where these factors had a significant effect were identified, and the results visualized. Across the entire innominate bone, the mean loss of density was found to be 1.6 mg/cc per year, with several specific areas (pubic body, iliac fossa, posterior ilium, and anterior inferior iliac spine for example) showing significant rates of loss up to three times greater than the rest of the bone. Areas significantly affected by sex included the posterior pubic root, anterior aspect of the pubic body, and iliac crest. Despite overall trends of attenuation, there remains significant variability between individuals. This supports the need to further explore subject-specific planning tools for pelvic fracture repair. Statement of clinical significance: Bone density changes across the innominate bone due to age and sex tend to vary between individuals, although consistent effects were seen at specific regions. This information may help in surgical planning of unstable fracture repairs.


Symmetry groupoids for pattern-selective feedback stabilization of the Chafee-Infante equation.
Reaction-diffusion equations are ubiquitous in various scientific domains and their patterns represent a fascinating area of investigation. However, many of these patterns are unstable and, therefore, challenging to observe. To overcome this limitation, we present new noninvasive feedback controls based on symmetry groupoids. As a concrete example, we employ these controls to selectively stabilize unstable equilibria of the Chafee-Infante equation under Dirichlet boundary conditions on the interval. Unlike conventional reflection-based control schemes, our approach incorporates additional symmetries that enable us to design new convolution controls for stabilization. By demonstrating the efficacy of our method, we provide a new tool for investigating and controlling systems with unstable patterns, with potential implications for a wide range of scientific disciplines.


In vivo performance evaluation and establishment of IVIVC for osmotic pump based extended release formulation of milnacipran HCl.
The objective of the present study was to carry out a pharmacokinetics evaluation of an oral modified release formulation [Aquarius EKX 19102 SRX-2 based osmotic pump (OP)] containing highly soluble milnacipran HCl (MH) as a model drug. It was also aimed at developing an in vitro-in vivo correlation (IVIVC) model for a developed OP. In vivo plasma concentration data were obtained from six healthy male New Zealand albino rabbits after administration of immediate-release milnacipran HCl solution (IRMHSOL) and milnacipran HCl osmotic pump (MHOP). In vitro samples were analysed using an in house developed spectrophotometry method and in vivo samples were analysed using a RP-HPLC method developed by the author. A deconvolution based Level A model was attempted through a correlation of the percent in vivo input obtained through deconvolution and the percent in vitro dissolution obtained experimentally. A good correlation between the percentages dissolved vs absorbed (R(2) = 0.978) was obtained using level A correlation. Evaluation of the internal predictability of level A correlation was calculated in terms of the percent prediction error, which was found to be below 15%. In a nutshell, the success of the present study warrants further studies in patient volunteers to assess the ability of the MHOP to provide an effective therapy for depression.


Risk factors for vaginal vault prolapse surgery in postmenopausal hysterectomized women.
The purpose of this study was to identify risk factors for surgery of vaginal vault prolapse in hysterectomized postmenopausal women. We conducted a case-control study. The cases were 117 consecutive postmenopausal hysterectomized women who underwent vaginal vault prolapse surgery at Danderyd Hospital or Karolinska Hospital, Stockholm, between 1996 and 2005. Control participants were 326 age-matched, randomly selected, hysterectomized women with no vaginal vault prolapse surgery, identified from the Swedish Inpatient Register. For participants and controls alike, data on determinants were extracted from patients' records, the Swedish Inpatient Register, and self-report questionnaires. Data were analyzed using nonparametric statistics and logistic regression. The questionnaire was returned by 90 of 117 participants (77%) and 233 of 326 controls (71%). The mean age at response to the questionnaire was 72.8 (+/- 9.7 SD) and 71.3 (+/- 8.7 SD) years for participants and controls, respectively. In a multivariate analysis, the only predictors at a significant level were age at hysterectomy (odds ratio = 1.04, 95% CI: 1.004-1.08), prolapse or incontinence surgery before hysterectomy (OR = 2.8, 95% CI: 1.0-7.7), and prolapse or incontinence surgery before vaginal vault surgery (OR = 9.1, 95% CI: 3.6-23.4). Postmenopausal women with surgically managed pelvic floor disorders are at increased risk of developing vaginal vault prolapse subsequent to a hysterectomy.


Prioritising to safeguard the integrity of nurse education.
Whether there are enough practice placements and if they are of a high enough quality are questions that continue to come up and their resolution is vital for the future of the nursing workforce as a whole. In view of the vast increases in student numbers expected over the next few years, innovation, rather than traditional solutions, seems the only option. The priorities for future preregistration nurse education must therefore be clearly focused and integrated if the integrity of preregistration nursing is to be safeguarded.


The effect of a semiocclusive dressing on the microbial population in superficial wounds.
Superficial wounds in a Yorkshire pig were treated with a semiocclusive polyurethane film dressing (PUD) or left open. The number and types of microflora present in the wounds each day was determined by a scrub technique, selective media, and the spiral plating system. In wounds covered with the PUD, the number of organisms increased, and there were more gram-negative pathogens. We concluded that microorganisms in wound beds multiply and survive better beneath a semiocclusive dressing than with air exposure.


Mesial temporal lobe epilepsy impairs advanced social cognition.
Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), investigations into advanced social cognitive abilities have been neglected. In the present study, we investigated the ability to detect social faux pas and studied possible mediating clinical and demographic variables in patients with MTLE compared with patients with an epilepsy not originating within the MTLE and healthy controls. The 27 MTLE patients (16 were investigated pre- and 11 postoperatively), 27 patients with an extramesiotemporal epilepsy (except frontal lobe epilepsy), and 12 healthy controls performed a shortened version of the faux-pas test. Additionally, we used standardized tests to measure intelligence. Only patients with intact reading-comprehension abilities were included in the study. MTLE patients, both pre- and postoperative, performed the faux-pas test significantly worse than patients with extramesiotemporal lobe epilepsy and healthy controls. The latter two groups showed comparable performance. No statistical association was found between the MTLE patients' deficit in recognizing a faux pas and the variables IQ, age, age at seizure onset, and duration of epilepsy. We report for the first time that patients with MTLE are specifically impaired in recognizing faux pas, suggesting that MTLE as such is a specific etiology of deficits in higher-order social cognition.


Safety of neural stem cell transplantation in patients with severe traumatic brain injury.
Neural stem cell (NSC) therapy is a promising treatment for traumatic brain injury (TBI). In addition, mesenchymal stem cells (MSCs) have been investigated for the treatment of TBI due to their functions in neural regeneration and their neurotrophic effect. In the present study, the safety, feasibility and biological effects of autologous MSC-derived NSC-like cell transplantation were investigated in 10 patients with severe TBI. All patients received intravenous or intrathecal injections of human NSC-like cells and were evaluated with physical and neurological examinations, routine laboratory tests and neuroradiological findings. The results indicated that the majority of patients experienced improved neurological function in different degrees during the follow-up period. No mortality or serious adverse events were observed in any patient subsequent to transplantation. Higher serum levels of nerve growth factor and brain-derived neurotrophic factor were detected following the transplantation, as compared with the levels prior to treatment. Overall, the present results suggest that transplantation of autologous NSC-like cells is feasible and appears to be safe for the treatment of non-acute severe TBI.


Assessing the Dynamics of Organic Aerosols over the North Atlantic Ocean.
The influence of aerosols on climate is highly dependent on the particle size distribution, concentration, and composition. In particular, the latter influences their ability to act as cloud condensation nuclei, whereby they impact cloud coverage and precipitation. Here, we simultaneously measured the concentration of aerosols from sea spray over the North Atlantic on board the exhaust-free solar-powered vessel "PlanetSolar", and the sea surface physico-chemical parameters. We identified organic-bearing particles based on individual particle fluorescence spectra. Organic-bearing aerosols display specific spatio-temporal distributions as compared to total aerosols. We propose an empirical parameterization of the organic-bearing particle concentration, with a dependence on water salinity and sea-surface temperature only. We also show that a very rich mixture of organic aerosols is emitted from the sea surface. Such data will certainly contribute to providing further insight into the influence of aerosols on cloud formation, and be used as input for the improved modeling of aerosols and their role in global climate processes.


Coherent ratchets in driven Bose-Einstein condensates.
We study the response of a Bose-Einstein condensate to an unbiased periodic driving potential. By controlling the space and time symmetries of the driving we show how a directed current can be induced, producing a coherent quantum ratchet. Weak driving induces a regular behavior, and space and time symmetries must both be broken to produce a current. For strong driving, the behavior becomes chaotic and the resulting effective irreversibility means that it is unnecessary to explicitly break time symmetry. Spatial asymmetry alone is then sufficient to produce the ratchet effect, even in the absence of interactions, and although the system remains completely coherent.


[Morphological and ultrastructural changes in the lungs as affected by different shock-producing factors].
Experiments on 234 guinea-pigs were made to study the effects of 3 shock-inducing agents (acute hemorrhage, graded chest injury, Salmonella endotoxin). Application of histological methods, electron microscopy, electron histochemistry with the use of rutenium red and Pattle 's method for determining the stability of pulmonary vesicles disclosed that the typical reaction seen within the first 6 hours was the spasm of bronchioles and venules, followed by the development of bilateral small-focal contractile atelectases and microcirculatory disorders in the form of the sludge syndrome, leukostasis, accumulation of megakaryocytes, DVS , and dystrophy of the capillary endothelium. Following 12-24 hours structural changes in the surfactant system supervened: the loss of lamillar bodies by large alveolocytes, disorganization of the surfactant film, a critical fall of the Pattle stability. Intraalveolar edema was recorded at the ultrastructural level after 6-12 hours and at the histological level after 24 hours. The degree and time of the development of the changes depended on the type of a shock-inducing agent.


Evaluation of Initial Respiratory Support Strategies in VLBW Neonates with RDS.
Non-invasive ventilation (NIV) has brought about a significant change in care and treatment of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates. The present study was designed and conducted to evaluate different strategies of initial respiratory support (IRS) in VLBW neonates hospitalized in the neonatal intensive care unit (NICU). This prospective study was conducted over three years (March 21, 2011 to March 20, 2014). Each eligible VLBW baby with RDS diagnosis received a specific IRS, including room air (RA), oxygen therapy (O2 RX), n.CPAP, NIPPV, MV ± SURF, based on clinical evaluation; then, the next strategies were selected based on the disease progression. Obtained data was entered in SPSS and the groups were compared for disease consequences or death. Then, contributing factors to the failure of NIV strategies, and the need for endotracheal mechanical ventilation (eMV) were determined. In total, 499 neonates were included in the study. The mean birth weight was 1,125 ± 254 g and the gestational age was 29.2 ± 2.5 weeks. The IRS included: RA = 43, O2.RX = 60, n.CPAP/NIPPV = 219, INSURE = 83 and MV ± SURF = 177. In terms of the need for IRS upgrading during hospitalization, neonates not on mechanical ventilation (64.5%) were divided into three groups. In 45.3% of cases, the IRS did not change (Never upgrading); in 24.5% of cases, the level of IRS increased but there was no need for eMV in the first three days of life (Specific); in 24.8% of cases, there was need for eMV within the first three days of life (Absolute) and during hospitalization (after the first three days of life) 5.3% of cases were in need of eMV (General). In terms of correlation between the effective variables in IRS upgrading, univariable analyses showed that low gestational age, low birth weight, multiple pregnancy, maternal disease, low one-minute Apgar score, and need for surfactant therapy had significant correlation, and multivariable analysis showed that low gestational age, low birth weight and maternal disease were risk factors independently correlated to IRS upgrading, CLD and death. Early use of NIV in preterm neonates with mild to moderate respiratory distress and spontaneous breathing significantly reduced the need for intubation, surfactant, mechanical ventilation and thereby pulmonary and non-pulmonary complications and neonatal mortality.


Age and efficacy of remote ischemic conditioning in acute ischemic stroke.
A post hoc analysis of RICAMIS trial to evaluate functional outcomes in relation to patient age. Patients in RICAMIS were divided into six age groups. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0-1. Compared with patients receiving usual care alone, we investigated the association of remote ischemic conditioning (RIC) effect with functional outcomes in each group and the interaction between RIC effect and age. Of 1776 patients, 498 were assigned to <60 years, 326 to 60 to <65 years, 325 to 65 to <70 years, 278 to 70 to <75 years, 206 to 75 to <80 years, and 143 to ≥80 years. Higher proportions of primary outcome were found associated with RIC in <60 years group (72.6% vs. 64.8%; adjusted risk difference [RD], 6.8%; 95% CI, -1.6% to 15.1%; p = 0.11), 60 to <65 years group (70.7% vs. 67.1%; adjusted RD, 3.1%; 95% CI, -7.2% to 13.3%; p = 0.56), 65 to <70 years group (70.5% vs. 63.6%; adjusted RD, 3.5%; 95% CI, -6.8% to 13.8%; p = 0.51), 70 to <75 years group (59.7% vs. 54.9%; adjusted RD, 4.7%; 95% CI, -7.1% to 16.4%; p = 0.61), 75 to <80 years group (61.5% vs. 55.9%; adjusted RD, 5.7%; 95% CI, -7.8% to 19.1%; p = 0.41), and ≥ 80 years group (59.2% vs. 59.7%; adjusted RD, -2.6%; 95% CI, -18.8% to 13.5%; p = 0.75). No significant interaction between RIC effect and age was found among groups. This is the first report that RIC effect may be attenuated with increasing age in patients with acute moderate ischemic stroke with respect to functional outcome.


Seroprevalence, cross antigenicity and circulation sphere of bat-borne hantaviruses revealed by serological and antigenic analyses.
Bats are newly identified reservoirs of hantaviruses (HVs) among which very divergent HVs have been discovered in recent years. However, their significance for public health remains unclear since their seroprevalence as well as antigenic relationship with human-infecting HVs have not been investigated. In the present study archived tissues of 1,419 bats of 22 species from 6 families collected in 5 south and southwest provinces in China were screened by pan-HV RT-PCR following viral metagenomic analysis. As a result nine HVs have been identified in two bat species in two provinces and phylogenetically classified into two species, Laibin virus (LAIV, ICTV approved species, 1 strain) and Xuan son virus (XSV, proposed species, 8 strains). Additionally, 709 serum samples of these bats were also analyzed by ELISA to investigate the seroprevalence and cross-reactivity between different HVs using expressed recombinant nucleocapsid proteins (rNPs) of LAIV, XSV and Seoul virus (SEOV). The cross-reactivity of some bat sera were further confirmed by western blot (WB) using three rNPs followed by fluorescent antibody virus neutralization test (FAVNT) against live SEOV. Results showed that the total HV seropositive rate of bat sera was 18.5% (131/709) with many cross reacting with two or all three rNPs and several able to neutralize SEOV. WB analysis using the three rNPs and their specific hyperimmune sera demonstrated cross-reactivity between XSV/SEOV and LAIV/XSV, but not LAIV/SEOV, indicating that XSV is antigenically closer to human-infecting HVs. In addition a study of the distribution of the viruses identified an area covering the region between Chinese Guangxi and North Vietnam, in which XSV and LAIV circulate within different bat colonies with a high seroprevalence. A circulation sphere of bat-borne HVs has therefore been proposed.


[Antitumor activity of howiinol (GHM-10) on L1210 cells in vitro].
Howiinol(GHM-10) is a new compound isolated from Goniothalamus howii. Previous studies showed that GHM-10 significantly inhibited the growth of cancer cells both in vitro and in vivo. In the present study, the characteristics of the inhibitory effect of GHM-10 on L1210 cells was investigated. The results showed that the IC50 of L1210 cells treated with GHM-10 for 1 h, 24 h, and 7 d was 6.85, 3.32 and 1.59 micrograms.ml-1, respectively. This outcome is in compliance with the hypothesis that GHM-10 is a cell cycle non-specific cytotoxic drug. When L1210 cells were treated with 1-2 micrograms.ml-1 of GHM-10 for 24 h, the growth rate and mitotic index were decreased and the morphology of cell nuclei changed, but the cell viability remained at the level of 96% or more, indicating that GHM-10 mainly inhibited cell proliferation. The cell cycle kinetics of L1210 cells were studied by using a flow cytometer. The results showed that the transition of cells from G1 phase to S phase was blocked to certain extent by the treatment of GHM-10 4 micrograms.ml-1 for 12 h. The fluidity of cell membrane was also increased when the L1210 cells were exposed to 2-3 micrograms.ml-1 of GHM-10 for 24 h.


Polarization eigenstates analysis of helically structured thin films.
The optical properties of thin films are generally determined by direct photometric quantities. We show that additional insight into the properties of anisotropic thin films can be obtained by computing the polarization eigenstates and eigenvalues of their Jones matrices. We consider helically structured thin films, which display intriguing optical response, such as the circular Bragg resonance. Using numerical simulations and actual measurements, we show that the eigenvectors are mutually orthogonal in most regions of the wavevector space, except near the circular Bragg and the oblique resonances. Special wavevector values, called exceptional points, are found where the Jones matrix becomes defective and its eigenvectors coalesce. Exceptional points are also found in pairs of wavevector values differing only by a sample rotation by π around the direction normal to the sample; this property is shown to arise from Saxton - de Hoop's reciprocity principle, which applies to lossy materials and contains time reversal symmetry, which only applies to lossless materials, as a special case.


Manifestations of cystic fibrosis diagnosed in adulthood.
This review highlights the phenotypic features that lead to the diagnosis of cystic fibrosis in adults, and the prognosis of these patients. With the widespread availability of genetic testing and a greater appreciation of the clinical spectrum of the disease, the diagnosis of cystic fibrosis is being made with increasing frequency in adults. Clinical features that lead to the diagnosis include respiratory symptoms and chronic airway infection with typical cystic fibrosis pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus, as well as nontuberculous mycobacteria. Often these patients have previously received diagnoses of asthma, chronic bronchitis, or emphysema. Pancreatic insufficiency is much less common in the adult receiving the diagnosis, but pancreatitis occurs with greater frequency. Occasionally, individuals receive diagnoses of apparent single-organ manifestations such as idiopathic pancreatitis or congenital bilateral absence of the vas deferens, but with negligible involvement of the respiratory tract. On rare occasions, patients receiving the diagnosis as adults can present with classic features of the disease. Although lung disease is generally less severe in cystic fibrosis patients receiving the diagnosis as adults than in adult patients who received the diagnosis as infants, the extent of bronchiectasis can nonetheless be severe. The clinical course of patients receiving a diagnosis of cystic fibrosis in adulthood is largely unknown, but frequently they have milder disease and a more favorable prognosis. Clinicians must be aware of the potential for adults with chronic respiratory tract infections, unexplained bronchiectasis, congenital bilateral absence of the vas deferens, or pancreatitis to have cystic fibrosis despite the age at presentation.


What's new and not so new on the antimicrobial horizon?
Despite increasing antimicrobial resistance and multiple drug resistance in clinical isolates of both Gram-positive and Gram-negative bacteria, there are few novel antimicrobial agents in development. The few new agents that have been recently licensed have tended to have narrow spectra of activity, focused on Gram-positive pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA). This situation is rightly causing concern among clinicians and public health authorities worldwide. This article reviews available data on three new antibacterials currently in development. The cephalosporin ceftobiprole is active against MRSA, Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae, but otherwise has a spectrum of activity similar to that of other recent cephalosporins. In a clinical trial, ceftobiprole was non-inferior to vancomycin for the treatment of MRSA-associated complicated skin and skin structure infections (cSSSIs). Doripenem, a new carbapenem, has some activity against MRSA, but otherwise has an anti-Gram-positive spectrum of activity similar to that of imipenem and an anti-Gram-negative spectrum similar to that of meropenem. In a clinical trial, it was non-inferior to meropenem for the treatment of complicated intra-abdominal infections. Iclaprim is a dihydrofolate reductase inhibitor with greatly enhanced activity, as compared with trimethoprim, against a range of Gram-positive and Gram-negative pathogens. The limited literature concerning this agent has concentrated on its potential role in the treatment of infections with Gram-positive bacteria. A clinical trial has demonstrated the non-inferiority of iclaprim, as compared with linezolid, in the treatment of cSSSIs, including those associated with MRSA.


Characterization of the physical stability of a lyophilized IgG1 mAb after accelerated shipping-like stress.
Upon exposure to shaking stress, an IgG1 mAb formulation in both the liquid and lyophilized state formed subvisible particles. Because freeze-drying was expected to minimize protein physical instability under these conditions, the extent and nature of aggregate formation in the lyophilized preparation were examined using a variety of particle characterization techniques. The effects of formulation variables such as residual moisture content, reconstitution rate, and reconstitution medium were also examined. Upon reconstitution of shake-stressed lyophilized mAb, differences in protein particle size and number were observed by microflow digital imaging, with the reconstitution medium having the largest impact. Shake stress had minor effects on the structure of protein within the particles as shown by SDS-PAGE and FTIR analysis. The lyophilized mAb was shake stressed to different extents and stored for 3 months at different temperatures. Both extent of cake collapse and storage temperature affected the physical stability of the shake-stressed lyophilized mAb upon subsequent storage. These findings demonstrate that physical degradation upon shaking of a lyophilized IgG1 mAb formulation includes not only cake breakage, but also results in an increase in subvisible particles and turbidity upon reconstitution. The shake-induced cake breakage of the lyophilized IgG1 mAb formulation also resulted in decreased physical stability upon storage.


Identification and quantification of organic vapors by time-resolved diffusion in stacked mesoporous photonic crystals.
Microsensors for gas-phase analytes are fundamentally limited by their inability to discriminate between analytes. While cross-reactive arrays consisting of multiple different sensor elements provide one means to identify individual analytes, these "artificial nose" devices rely on complicated data processing algorithms and they generally suffer from significant zero-point drift. Herein, we present a single component optical sensor that is capable of identifying chemical compounds at parts-per-million concentrations. The device consists of a stack of three mesoporous silicon-based photonic crystals; a porous "drift tube" is sandwiched between two optically responsive layers. The drift layer temporally separates the optical responses of the other layers, and this difference is shown to be characteristic of the analyte.


Electronic dimensions of FeMo-co, the active site of nitrogenase, and its catalytic intermediates.
The iron-molybdenum cofactor (FeMo-co), which is the catalytic center for the enzymatic conversion of N(2) to NH(3), has the composition [NFe(7)MoS(9)(homocitrate)], and, with a cluster of eight transition metal atoms and nine sulfur atoms, has a complex delocalized electronic structure. The electronic dimensions of FeMo-co and of each of its derivatives appear as sets of electronic states lying close in energy. These electronic dimensions naturally partner the geometrical changes and the reactivity patterns during the catalytic cycle, and also connect with spectroscopic investigations of the mechanism. This paper describes straightforward computational procedures for the determination and management of the low-lying electronic states of FeMo-co and of its coordinated intermediates and transition states during density functional simulations of steps in the catalytic mechanism. General principles for the distribution of electron spin density over all atoms are presented, using several proposed intermediates as examples. A tough general irony arises in the distribution of spin density over FeMo-co and its derivatives: the less interesting atoms get the spin, and the most interesting atoms do not.


Novel SNPs of butyrophilin (BTN1A1) and milk fat globule epidermal growth factor (EGF) 8 (MFG-E8) are associated with milk traits in dairy goat.
Butyrophilin (BTN1A1) and milk fat globule epidermal growth factor (EGF) 8 (MFG-E8) genes are both milk fat globule membrane proteins. BTN1A1 plays a key role in the secretion of milk lipid and production which has effects on performance traits, while the MFG-E8 is vital for the development of the mammary gland and phagocytic clearance of apoptotic cells. Therefore, BTN1A1 and MFG-E8 gene are candidate genes for quantitative traits in mammalian animals with respect to milk performance traits. The objective of this study is to investigate variations in goat BTN1A1 and MFG-E8 gene and analyze their associations with growth trait and milk performance. In this study, the goat BTN1A1 gene showed a novel single-nucleotide polymorphism (SNP): XM_001494179:g.8659C>T, resulting in a missense mutation: CTT (Leu)>TTT (Phe) at position 377 aa of the BTN1A1 (526 aa); the goat MFG-E8 gene showed four novel SNPs: NC_007319: g.843delA, 6417delC, 14892T>C and 14996A>C, only the 14892T>C result in a synonymous mutation. The associations between genotypes and production traits were analyzed. Significant statistical results implied that HinfI locus of BTN1A1 gene is associated with milk fat yield (P=0.004), total solid (P=0.002), solid-non fat (P=0.018) and first milk yield (P=0.030). The DA and EcoRV loci of MFG-E8 gene are associated with milk fat yield (DA locus: P=0.000; EcoRV locus: P=0.033) and total solid (DA locus: P=0.002; EcoRV locus: P=0.015) in the Xinong Saanen dairy goat.


Looking Further When Symptoms Are Disproportionate to Physical Findings.
A 36-yr-old man presents with left ulnar-side wrist pain during an ice hockey game that prevented him from playing hockey or golf. There was no acute mechanism of injury. The usual clinical examination revealed only minimal tenderness and minimal pain with resisted wrist extension. Careful attention to precipitating factors led to testing resisted wrist extension with the forearm fully supinated, which reliably reproduced the intensity of the patient's symptoms, and a diagnosis of extensor carpi ulnaris tendinopathy. A literature review suggested three additional special tests (two were positive) and management. However, a standard of care has yet been established because neither the tests nor the management has been properly validated through research, thus leaving the management of this condition as an art.


Improvement of the Laser-Welded Lap Joint of Dissimilar Mg Alloy and Cu by Incorporation of a Zn Interlayer.
During pulsed laser welding of AZ 31B magnesium (Mg) alloy and T2 pure copper (Cu), Cu2Mg and Mg2Cu are generated, but the bonding ability of the two compounds is usually weak, resulting in low strength. In order to improve the joint of two dissimilar metals, a zinc interlayer was inserted between the Mg alloy and Cu, and the effects of the thickness of the Zn interlayer on the microstructure and properties of the joint were studied. The fused zone consisted of Cu2Mg and MgZn, and, according to first-principles calculation, in the same energy range, the area enclosed by the density of the state curve of MgZn was larger than that of Cu2Mg. Hence, the bonding ability of MgZn was better than that of Cu2Mg, and MgZn improved the strength of the welded joint. The most advantageous thickness of the Zn interlayer was 0.1 mm, and the shear strength was 48.15 MPa that was 161% higher than that of the directly welded Mg/Cu joint.