A grounded theory exploration of undergraduate experiences of vicarious unemployment.
The experiences of vicarious unemployment (VU) among 17 undergraduate student participants who had a primary caregiver who was involuntarily unemployed were explored using grounded theory (Charmaz, 2006; Glaser & Strauss, 1967). Data from semistructured interviews with 15 women and 2 men revealed the nuanced nature of experiences with unemployment among those who experience it vicariously. Struggles related to increased family stress and experiences with stigma were common across participants. As participants reflected upon these challenges, they both lamented the costs associated with the struggles and expressed appreciation for the lessons that they have learned. They emerged from their VU experiences with increased financial and job market awareness, which informed their hope for a life that is free from the struggles endured in their families. Participants expressed confidence in their ability to cultivate financial security for their own families, stable employment, and opportunities to pursue work that will allow them to give back to others. Implications for counseling and directions for future research are discussed.


Mineralization and nutrient release pattern of vermicast-sawdust mixed media with or without addition of Trichoderma viride.
A combination of vermicast and sawdust mixed medium is commonly used in horticulture, but the added benefit of microbial inoculation and mechanism of nutrient availability are unknown. This study was done to determine nutrient mineralization and nutrient release patterns of different combinations or a mix of vermicast-sawdust growing media amended with or without Trichoderma viride (105 spores/g). The mixed-media treatments were (1) 80% vermicast+20% sawdust; (2) 60% vermicast+40% sawdust; (3) 40% vermicast+60% sawdust; (4) 20% vermicast+80% sawdust; and (5) sawdust alone (control). Total dissolved solids, electric conductivity and salinity increased with each sampling time following submergence in deionized. Nutrients released from media without T. viride were significantly higher than the corresponding media with added T. viride. Overall, the starting total nitrogen of the different media did not change during the incubation period, but nitrate-nitrogen was reduced to a negligible amount by the end of day 30 of incubation. A repeated measures analysis showed a significant effect of Time*T. viride*Treatment on total dissolved solids. Redundancy analysis demonstrated a positive and strong association between media composed of ≥40% vermicast and ≤60% sawdust with or without T. viride and mineral nutrients released, electrical conductivity, total dissolved solids and salinity. These findings suggest that fast-growing plants may benefit from 40% to 60% vermicast added to 40% to 60% sawdust without T. viride while slow-growing plants can benefit from the same mixed medium combined with the addition of T. viride. Further investigation is underway to assess microbial dynamics in the mixed media and their influence on plant growth.


[The role of serum neopterin level in the evaluation of activation and response to treatment in the patients with pulmonary tuberculosis].
Neopterin is an important parameter showing cell mediated immunity activation. In this study we aimed to determine whether serum neopterin level could be used as a marker in the evaluation of tuberculosis activation and response to treatment. The study comprised 40 new case smear positive pulmonary tuberculosis patients and 40 healthy control. Serum neopterin levels were measured both before the treatment and 2nd month of the treatment in the patient group. The association between serum neopterin level and clinical, radiological and bacteriological parameters were also investigated. In patients with pulmonary tuberculosis the mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and 21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients were significantly higher than the control group (p=0.001). Also, there was significant difference between serum neopterin levels before the treatment and the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the group with extensive disease than the cases with limited disease (p=0.02). In conclusion, we think that serum neopterin level might be used as a reliable immunological marker in the evaluation of tuberculosis activation and response to treatment.


Cell-impedance-based label-free technology for the identification of new drugs.
Drug discovery has progressed from relatively simple binding or activity screening assays to high-throughput screening of sophisticated compound libraries with emphasis on miniaturization and automation. The development of functional assays has enhanced the success rate in discovering novel drug molecules. Many technologies, originally based on radioactive labeling, have sequentially been replaced by methods based on fluorescence labeling. Recently, the focus has switched to label-free technologies in cell-based screening assays. Areas covered: Label-free, cell-impedance-based methods comprise of different technologies including surface plasmon resonance, mass spectrometry and biosensors applied for screening of anticancer drugs, G protein-coupled receptors, receptor tyrosine kinase and virus inhibitors, drug and nanoparticle cytotoxicity. Many of the developed methods have been used for high-throughput screening in cell lines. Cell viability and morphological damage prediction have been monitored in three-dimensional spheroid human HT-29 carcinoma cells and whole Schistosomula larvae. Expert opinion: Progress in label-free, cell-impedance-based technologies has facilitated drug screening and may enhance the discovery of potential novel drug molecules through, and improve target molecule identification in, alternative signal pathways. The variety of technologies to measure cellular responses through label-free cell-impedance based approaches all support future drug development and should provide excellent assets for finding better medicines.


Systemic effects resulting from topical ocular administration of SCH 33861, a novel ACE inhibitor ocular hypotensive agent.
SCH 33861 (7- N- 1(S)-(Carboxy)-3-phenylpropyl -(S)-alanyl 1,4-dithia-7-azaspiro 4.4 nonane-8(S)-carboxylic acid) is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with marked topical ocular hypotensive activity. The present study evaluated the degree of systemic ACE inhibition resulting from topical administration of 0.01 and 0.1% concentrations (10 and 100-fold greater than needed to lower IOP) of SCH 33861 in conscious rabbits. For reference purposes, captopril, a prototype ACE inhibitor, was examined at concentrations 5 and 20-fold greater than needed to lower IOP. Neither 0.01 nor 0.1% topical SCH 33861 led to inhibition of pressor responses to 0.3 micrograms/kg iv challenges with angiotensin I (AI) over a 4 hr period. Captopril, in contrast, caused significant attenuation of AI pressor responses. The magnitude and duration of systemic ACE inhibition following captopril administration was concentration related. Intravenous administration of the same dose administered topically did not cause any systemic ACE inhibition with 0.01% SCH 33861. Following iv 0.1% SCH 33861, 0.5 or 2.0% captopril, AI responses were inhibited 60-70% indicating the ability to inhibit ACE if any systemic absorption took place. Topical administration of 0.01% SCH 33861 twice daily for five days also did not produce systemic ACE inhibition. These findings indicate that topical amounts of SCH 33861 greatly in excess of those needed to effect reductions in IOP have an exceptionally low potential for producing systemic effects.


Assessment of insecticidal effects and selectivity of CAPA-PK peptide analogues against the peach-potato aphid and four beneficial insects following topical exposure.
Insect Capability neuropeptides (CAP2b/CAPA-PKs) play a critical role in modulating different physiologies and behavior in insects. In a previous proof-of-concept study, the CAP2b analogues 1895 (2Abf-Suc-FGPRLamide) and 2129 (2Abf-Suc-ATPRIamide) were reported to reduce aphid fitness when administered by injection. In the current study, the insecticidal efficacy of 1895 and 2129 on the peach potato aphid Myzus persicae was analyzed by topical application, simulating a spray application scenario in the field. Additionally, the selectivity of the tested analogues was evaluated against a selection of beneficial insects, namely three natural enemies (Adalia bipunctata, Chrysoperla carnea and Nasonia vitripennis) and a pollinator (Bombus terrestris). Within 3-5 days post topical exposure of aphids to 1895, higher mortality (33%) was observed, as was the case for the treatment with 2129 (17%) and the mixture of 1895 + 2129 (47%) compared to the control (3%). 1895 and the mix 1895 + 2129 showed the strongest and comparable insecticidal effects. Additionally, surviving aphids treated with 1895 showed a reduction in total lifetime reproduction (GRR) of 30%, 19% with 2129 and 39% with the mix 1895 + 2129. Of interest from a biosafety perspective is that by using the same delivery method and dose, no significant effects on survival, weight increase and food intake was observed for the representative natural enemies and the pollinator. This study highlights the potential of exploiting CAP2b analogues such as 1895 (core structure FGPRL) as aphicides. Additionally, the CAP2b analogues used in this study were selective as they showed no effects when applied on four representative beneficial insects.


ATM kinase activity modulates ITCH E3-ubiquitin ligase activity.
Ataxia Telangiectasia Mutated (ATM) kinase, a central regulator of the DNA damage response, regulates the activity of several E3-ubiquitin ligases, and the ubiquitination-proteasome system is a consistent target of ATM. ITCH is an E3-ubiquitin ligase that modulates the ubiquitination of several targets, therefore participating to the regulation of several cellular responses, such as the DNA damage response, tumor necrosis factorα (TNFα), Notch and Hedgehog signaling, and the differentiation of 'naive' lymphocytes into T helper type 2 cells. Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH. ATM activity enhances ITCH enzymatic activity, which in turn drives the ubiquitination and degradation of c-FLIP-L and c-Jun, previously identified as ITCH substrates. Importantly, ATM-deficient mice show resistance to hepatocyte cell death, similarly to Itch-deficient animals, providing in vivo genetic evidence for this circuit. Our data identify ITCH as a novel component of the ATM-dependent signaling pathway and suggest that the impairment of the correct functionality of ITCH caused by Atm deficiency may contribute to the complex clinical features linked to Ataxia Telangiectasia.


Psychoeducation for bipolar disorder: A discourse analysis.
Psychoeducation has become a common intervention within mental health settings. It aims to increase people's ability to manage a life with a long-term illness. For people with bipolar disorder, psychoeducation is one of a range of psychosocial interventions now considered part of contemporary mental health practice. It has taken on a 'common sense' status that results in little critique of psychoeducation practices. Using a published manual on psychoeducation and bipolar disorder as its data, Foucauldian discourse analysis was used in the present study for a critical perspective on psychoeducation in order to explore the taken-for-granted assumptions on which it is based. It identifies that the text produces three key subject positions for people with bipolar disorder. To practice self-management, a person must: (i) accept and recognize the authority of psychiatry to know them; (ii) come to see that they can moderate themselves; and (iii) see themselves as able to undertake a reflexive process of self-examination and change. These findings highlight the circular and discursive quality to the construct of insight that is central to how psychoeducation is practiced. Using Foucault's construct of pastoral power, it also draws attention to the asymmetrical nature of power relations between the clinician and the person with bipolar disorder. An effect of the use of medical discourse in psychoeducation is to limit its ability to work with ambivalence and contradiction. A critical approach to psychotherapy and education offers an alternate paradigm on which to basis psychoeducation practices.


Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer.
Preclinical studies showed metformin reduces exhaustion of tumor-infiltrating lymphocytes and potentiates programmed cell death protein-1 (PD-1) blockade. We hypothesized that metformin with nivolumab would elicit potent antitumor and immune modulatory activity in metastatic microsatellite stable (MSS) colorectal cancer (CRC). We evaluated this hypothesis in a phase II study. Nivolumab (480 mg) was administered intravenously every 4 weeks while metformin (1000 mg) was given orally, two times per day following a 14-day metformin only lead-in phase. Patients ≥18 years of age, with previously treated, stage IV MSS CRC, and Eastern Cooperative Oncology Group 0-1, having received no prior anti-PD-1 agent were eligible. The primary endpoint was overall response rate with secondary endpoints of overall survival (OS) and progression-free survival (PFS). Correlative studies using paired pretreatment/on-treatment biopsies and peripheral blood evaluated a series of immune biomarkers in the tumor microenvironment and systemic circulation using ChipCytometry and flow cytometry. A total of 24 patients were enrolled, 6 patients were replaced per protocol, 18 patients had evaluable disease. Of the 18 evaluable patients, 11/18 (61%) were women and the median age was 58 (IQR 50-67). Two patients had stable disease, but no patients had objective response, hence the study was stopped for futility. Median OS and PFS was 5.2 months (95% CI (3.2 to 11.7)) and 2.3 months (95% CI (1.7 to 2.3)). Most common grade 3/4 toxicities: Anemia (n=2), diarrhea (n=2), and fever (n=2). Metformin alone failed to increase the infiltration of T-cell subsets in the tumor, but combined metformin and nivolumab increased percentages of tumor-infiltrating leukocytes (p=0.031). Dual treatment also increased Tim3+ levels in patient tissues and decreased naïve CD8+T cells (p=0.0475). Nivolumab and metformin were well tolerated in patients with MSS CRC but had no evidence of efficacy. Correlative studies did not reveal an appreciable degree of immune modulation from metformin alone, but showed trends in tumorous T-cell infiltration as a result of dual metformin and PD-1 blockade despite progression in a majority of patients.


Invasive benign meningioma: Clinical characteristics, surgical strategies and outcomes from a single neurosurgical institute.
The aim of the present study was to improve the prognosis for patients with invasive benign meningioma by increasing the precision of pre-operative evaluation and refining the surgical resection strategy. A retrospective review of all the cases of invasive benign meningioma admitted to a single institute from 2005 to 2010 was conducted. The clinical characteristics, magnetic resonance imaging (MRI) findings, refined surgical strategies and outcomes were summarized and analyzed. There were 19 cases of invasive benign meningioma among 254 cases of meningioma. Of the earliest 4 cases, a traditional extra-capsular surgical removal approach was applied, which resulted in permanent neurological deficits for all cases. A modified surgical strategy combining intra- and extra-capsular resection techniques was employed for the subsequent 15 cases, which lead to mild neurological impairment in only 1 case. Pre-operative recognition of this unique sub-type of meningioma maybe facilitated by its typical MRI study findings, and the combination of intra- and extra-capsular resection techniques may be of critical importance in achieving complete tumor removal while maintaining intact neurological functions.


Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents.
Branched copolymer nanoparticles (D(h) =20-35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition-fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest molecules, which could allow simultaneous bioimaging and drug delivery.


Mycotic aortic aneurysms treated by endovascular repair: initial experience in a single center.
Mycotic aortic aneurysm (MAA) is an uncommon cause of aneurysmal aortic disease. However, it may have an aggressive presentation and a complicated early outcome. Endovascular aneurysm repair (EVAR) of MAA is emerging as an alternative to open repair (OR) for the treatment of these aneurysms, particularly in high-risk surgical patients. We report a single-center experience with the endovascular management of mycotic aortic aneurysms. Two mycotic abdominal aortic aneurysms were treated with an endovascular stent graft at Centre Hospitalier Régional du Val de Sambre, Belgium. The mean follow-up was 15 months. Technical success was achieved in all two patients. CT-scan follow up showed shrinkage of the aneurysm sac, with no evidence of infection along the stent graft and no signs of endoleakage in all patients. One patient died during the follow-up period from a cause unrelated to the aneurysm. EVAR is an effective and safe option and might be a suitable alternative to OR in the absence of predictors of poor prognosis for the treatment of non-complicated forms of MAA.


Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.
Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.


Surgical treatment of a mixed pineocytoma/pineoblastoma in a 72-year-old patient.
Although pineal parenchymal tumours are very rare in elderly patients, we recently successfully treated a 72-year-old male patient. Interestingly, the histology of his pineal parenchymal tumour was mixed pineocytoma/pineoblastoma, which is reported to be extremely rare in aged patients. We present his clinical manifestations, follow-up MRI, surgical treatment, pathological findings, and review the literature. This 72-year-old man had a mass in the pineal region detected 3 years previously on MRI in February 1996 following symptoms of headache and vertigo. Two years later, he experienced gait disturbance and disorientation. CT scans disclosed obstructive hydrocephalus, and ventriculo-peritoneal shunt placement was then performed. The tumour mass began to enlarge in July 1999 (at age 72). On October 13, 1999, total removal of the pineal region tumour was performed through an occipital transtentorial approach. The postoperative course was uneventful. The pathological diagnosis of the tumour was mixed pineocytoma/pineoblastoma. Pineal parenchymal tumours are uncommon in elderly patients, and mixed pineocytoma/pineoblastomas are particularly rare. We followed this patient closely for more than 3.5 years and finally performed total surgical removal of the tumour, with excellent outcome. The present case suggests that a mixed pineocytoma/pineoblastoma tumour is controllable even in elderly patients through careful evaluation and management.


Exploring Discrepancies in Perceived Nursing Competence Between Postgraduate-Year Nurses and Their Preceptors.
Postgraduate clinical training programs improve the core competence of nurses. How postgraduate-year (PGY) nurses perceive their clinical competence and their preceptors' perceptions may affect program effectiveness. This study compared the perspectives of clinical competencies of PGY nurses engaged in a residency program in Taiwan with their preceptors' perspectives. A cross-sectional study was conducted at a medical center in Taiwan. The Nursing Competence Questionnaire was used to obtain data from 99 pairs of PGY nurses and preceptors. PGY nurses' scores were higher than their preceptors' for communication, patient education, and management competencies (p <.05). Preceptors with more years of clinical experience exhibited greater assessment discrepancies for clinical care, communication, patient education, research awareness, and overall competence (p <.05). Preceptor development courses should be grounded in a strong pedagogical framework. An assessment tool with explicit behavioral indicators would be needed for objective evaluation from both perspectives. J Contin Educ Nurs. 2017;48(4):190-196.


There is still a role for cytology in the 'liquid biopsy' era. A lesson from a TKI-treated patient showing adenocarcinoma to squamous cell carcinoma transition during disease progression.
Non-small cell lung carcinoma harbouring epidermal growth factor receptor (EGFR) mutation, usually progress after an initial response to tyrosine-kinase inhibitors (TKI). Liquid biopsy enables with a simple blood draw the accurate detection of EGFR p.T790M mutation, the most common resistance mechanism, avoiding the more invasive tissue re-biopsy. However, in a subset of cases, resistance mechanisms are more complex featuring both genetic and morphological changes. Here we report the case of a 67 years-old woman, affected by an EGFR mutated lung adenocarcinoma and treated by TKI. At disease progression, the patient developed a morphological transition to squamous cell carcinoma in association to the arising of a PIK3CA p.E542K mutant subclone. This case illustrates that, even in the "liquid biopsy" era, cytology can have still a role by providing an overall assessment of both morphology and genetic TKI resistance mechanisms.


Pulsatile gonadotrophin secretion in hypothyroid women of reproductive age.
Hypothyroid women may have various disturbances of the reproductive system. Although menstrual cycle disturbances and infertility have been reported in hypothyroidism, gonadotrophin levels have usually been found in the normal range. We have investigated whether female hypothyroid patients of reproductive age have any alteration in the pulsatile secretory pattern of gonadotrophin secretion. LH and FSH were assayed on days 2-5 of the menstrual cycle in blood samples taken every 10 min for 8 h from six hypothyroid women and six age-matched control subjects. Pulsatility was analysed using the Cluster and Detect programs. There was no significant difference in the number of peaks identified (3.7 +/- 0.8 vs 3.7 +/- 0.8 for LH, and 3.7 +/- 0.8 vs 4.2 +/- 0.5 for ESH), the mean duration of peaks (LH: 68.0 +/- 6.9 vs 72.7 +/- 5.1 min; FSH: 81.9 +/- 8.1 vs 71.2 +/- 10.3 min), the area under the peaks (LH: 91.5 +/- 20.4 vs 148.2 +/- 55.1 IU/l per min; FSH: 71.5 +/- 4.5 vs 62.7 +/- 15.0 IU/l per min), and the incremental amplitude from baseline (LH: 2.2 +/- 0.4 vs 3.0 +/- 0.8 IU/l; FSH: 1.4 +/- 0.2 vs 2.1 +/- 0.5 IU/ l). However, the absolute pulse amplitude was greater in hypothyroid patients (LH: 14.5 +/- 1.4 vs 8.3 +/- 1.3 IU/l, P < 0.01; FSH: 9.0 +/- 1.5 vs 5.8 +/- 1.2 IU/l, P = 0.04), as were the integrated concentrations (LH: 6.6 +/- 0.7 vs 3.2 +/- 0.4 IU/l per min, P < 0.01; FSH: 4.3 +/- 0.4 vs 2.1 +/- 0.5 IU/l per min, P < 0.01). Oestradiol values were comparable in the two groups (42.7 +/- 0.4 vs 43.5 +/- 9.7 pg/ml). These results indicate that in hypothyroid women there is an increased baseline level with a normal pulsatility of the gonadotrophin secretion. Similar oestrogen levels in both groups, and normal or near-normal cycles in our patients suggest either a decreased biological potency of the gonadotrophins or a mild ovarian resistance.


Prevalence of byssinosis and other respiratory problems among textile mill workers in Asaba, Nigeria.
This study was conducted to determine the distribution and severity of byssinosis and other respiratory problems in the different operation sections in a textile mill industry in Asaba. This is a cross-sectional and analytic study in which workers directly exposed to cotton dust are compared with those not directly exposed to cotton dust at one point in time. A total of 735 workers were interviewed and 437 workers had respiratory examinations carried out on them. Byssinosis was diagnosed in 8 out of 405 workers (prevalence of 1.98%) who were not directly exposed to cotton dust, and 21 out of 330 workers (prevalence of 6.36%) who were directly exposed to cotton dust. The difference was found to be statistically significant (chi2 =9.25; df=1; 0.01<p<0.001). The spinning department had the highest prevalence of 11.5%. The prevalence of respiratory abnormalities which did not necessarily meet the criteria for a diagnosis of byssinosis was 4.9% for persistent cough and persistent phlegm; 8.0% for dyspnoea grade 2+; 3.3% for dyspnoea grade 4 and 2.59% for dyspnoea grade 5. Smoking was not found to be associated with the disease as none of the byssinotics were current smokers Byssinosis and other respiratory problems were found to be more prevalent in sections of the textile mill industry that were directly exposed to cotton dust. These findings form a basis for making suitable recommendations for the prevention of byssinosis and respiratory diseases in textile mills in Nigeria.


New assays for the tyrosine hydroxylase and dopa oxidase activities of tyrosinase.
New assays for the tyrosine hydroxylase and dopa oxidase activities of tyrosinase (EC 188.8.131.52) have been developed. The tyrosine hydroxylase assay uses L-[carboxy-14C]tyrosine as the substrate, 14CO2 is released from the products of the hydroxylation and further metabolism of L-[carboxy-14C]tyrosine by incubation with ferricyanide, and measured radiometrically. D-Dopa is a preferable cofactor to L-dopa for the assay. Dopa oxidase activity is measured spectrophotometrically. Dopaquinone, produced on the oxidation of L-dopa, reacts with Besthorn's hydrazone (3-methyl-2-benzothiazolinone hydrazone) to form a pink pigment with an absorbance maximum at 505 nm. Details of the optimisation of conditions for the assays and their specificities for the two enzyme activities are described.


EVOLUTION OF INFLORESCENCE DESIGN: THEORY AND DATA.
Very low fruit set in milkweeds and other flowering plants often has been attributed to greater sexual selection on inflorescence size via male, rather than female, reproductive success. Although this explanation has been generally accepted, alternate explanations have been presented, and recently the "male function" or "pollen donation" hypothesis has been sharply criticized. In this paper, we make the distinction between selection on total flower number and on the size of inflorescence units, both of which have been termed "inflorescence size." We present an ESS model for the evolution of inflorescence design that considers reproductive success through male and female function. The model predicts that selection will balance the proportional changes in female and male reproductive success resulting from changes in inflorescence-unit size. We conducted a field study of selection on the size of inflorescence units (umbels) by manipulating umbel size and number in a natural population of Asclepias tuberosa, in southeastern Arizona, during two reproductive seasons. We found that the male fitness function reached a maximum at an intermediate umbel size in both years (although not significantly different from the smallest umbel size in either year), whereas the female fitness function was highest for the smallest umbel size in one year, but was constant across umbel sizes in the other year. We also found that pollinator visitation rate corresponded well with male, but not female, function, and that between-year variation in the male reproductive success of different umbel sizes corresponded with variation in the composition of the pollinator pool. Our empirical results, when inserted in the model, predict ESS umbel sizes similar to those observed in the study population and the species throughout its range.


Effect of detoxified karanja (Pongamia spp.) cake on testicular architecture and semen production in ram lambs.
The protein-rich non-conventional detoxified karanja cake (dKC) can be used in place of conventional protein supplements like soybean meal (SBM), groundnut meal, etc. in livestock feed. The present study was conducted to assess the effect of two levels of dKC by replacing SBM on testicular architecture, semen quality and expressions of mRNAs encoding luteinizing hormone receptor (LHR) and insulin-like growth factor (IGF-I) in testes of ram lambs. Eighteen ram lambs were randomly divided into three groups (n = 6) and fed different levels (%) of karanja cake (0% replacement--control; 50% replacement--dKC-50 and 75% replacement--dKC-75) for 140 days. After 120 days of feeding, the semen from the animals was collected and analysed. The testes samples were collected on day 140 of feeding for transcripts expression studies. The dKC-50 group had no change in BW, whereas dKC-75 group showed decreased (P < 0.05) BW as compared with control. The number of animals ejaculated semen in dKC-75 group was lower (P < 0.05) than the control group. A reduction (P < 0.05) in LHR expression in dKC-75 was observed, whereas a reduction in IGF-I expression (P < 0.05) was observed in dKC-50 and dKC-75 as compared with control group. The study reveals that in ram lambs, long-term feeding of dKC at 50% replacement of SBM may not affect BW. However, long-term feeding of dKC as a replacement of SBM may affect testicular function.


Aberrant interhemispheric functional reciprocities of the default mode network and motor network in subcortical ischemic stroke patients with motor impairment: A longitudinal study.
The purpose of the present study was to explore the longitudinal changes in functional homotopy in the default mode network (DMN) and motor network and its relationships with clinical characteristics in patients with stroke. Resting-state functional magnetic resonance imaging was performed in stroke patients with subcortical ischemic lesions and healthy controls. The voxel-mirrored homotopic connectivity (VMHC) method was used to examine the differences in functional homotopy in patients with stroke between the two time points. Support vector machine (SVM) and correlation analyses were also applied to investigate whether the detected significant changes in VMHC were the specific feature in patients with stroke. The patients with stroke had significantly lower VMHC in the DMN and motor-related regions than the controls, including in the precuneus, parahippocampus, precentral gyrus, supplementary motor area, and middle frontal gyrus. Longitudinal analysis revealed that the impaired VMHC of the superior precuneus showed a significant increase at the second time point, which was no longer significantly different from the controls. Between the two time points, the changes in VMHC in the superior precuneus were significantly correlated with the changes in clinical scores. SVM analysis revealed that the VMHC of the superior precuneus could be used to correctly identify the patients with stroke from the controls with a statistically significant accuracy of 81.25% (P ≤ 0.003). Our findings indicated that the increased VMHC in the superior precuneus could be regarded as the neuroimaging manifestation of functional recovery. The significant correlation and the discriminative power in classification results might provide novel evidence to understand the neural mechanisms responsible for brain reorganization after stroke.


Bicarbonate transport along the loop of Henle: molecular mechanisms and regulation.
The loop of Henle (LOH) is an important site of renal tubule acidification. A combination of several techniques, including in vivo microperfusion, perfusion in vitro of the S3 segment of the proximal tubule and of the thick ascending limb (TAL) of Henle's loop, as well as quantitative PCR performed on isolated TAL, has permitted the definition of key transporters and their role in modulating bicarbonate reabsorption in physiological and pathophysiological conditions. Na(+)-H+ exchange is the most important transport mechanism responsible for bicarbonate reabsorption, although a small but significant contribution of H(+)-ATPase-mediated bicarbonate reabsorption can also be identified. NHE3 is the main of several NHE isoforms expressed in the TAL and in the S3 segment of the proximal tubule. Special properties of the Na(+)-H+ exchanger in the TAL are its relative insensitivity to changes in cell pH (pHi) and the tight coupling between apical and basolateral Na(+)-H+ exchange. Several hormones, including anti-diuretic hormone (ADH), angiotensin II (AII), and gluco- and mineralocorticoids regulate Na(+)-H+ exchange. Loop diuretics such as furosemide stimulate bicarbonate transport along the LOH. Systemic acid-base disturbances also modulate bicarbonate transport: acidosis increases bicarbonate reabsorption, while metabolic alkalosis has the opposite effect. Neither hypokalemic alkalosis nor respiratory alkalosis or respiratory acidosis alter bicarbonate transport along the LOH. A significant role of HCO3 backflux, most likely through the paracellular pathway of the TAL, can also be observed. Changes in extracellular osmolality also affect bicarbonate reabsorption: hypertonicity inhibits, whereas hypotonicity stimulates transport. Transport activation is also observed as an adaptive response to glomerular hyperfiltration.


Intermediate stage Hodgkin lymphoma in partial remission after three or four courses of doxorubicin, bleomycin, vinblastine dacarbazine: no benefit of one course of intensive chemotherapy before irradiation.
The H97-I trial (1997-2004) for Hodgkin lymphoma at intermediate stage (HL-I) included 269 patients who were randomized to receive three or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The 197 patients who reached complete remission (CR) (73.2%, p = 0.41 between arms) received radiotherapy (RT); their 10-year progression-free survival (PFS) rate was 87.7 ± 3.0%, similar to that of the 180 patients of a historical control group (HCG) in CR after three ABVD cycles before RT. The 59 patients who reached post-ABVD partial remission (PR) received one course of intensive chemotherapy (i.v., mg/m(2), vindesine 5, adriamycin 90, BCNU 140, etoposide 600, methylprednisolone 600) before RT. In spite of this additional intensive chemotherapy, their PFS rate (78.4 ± 6.3%) remained significantly lower (p = 0.03) than that of the 197 patients who reached post-ABVD CR, and was similar to that of the 60 patients of the HCG in PR after three ABVD cycles who did not receive additional chemotherapy before RT.


Progressive isthmus delay during atrial flutter ablation: the critical importance of isthmus spanning electrodes for distinguishing pseudoblock from block.
Bidirectional isthmus block is associated with successful atrial flutter ablation, whereas creation of increased isthmus conduction delay without block can be proarrhythmic. Often, halo catheter electrodes fail to provide adequate sub-Eustachian isthmus recordings. The aim of this study was to determine if progressive isthmus conduction delay results in the false appearance of block during atrialflutter ablation. A 20-pole deflectable catheter was prospectively positioned across the sub-Eustachian isthmus (from the coronary sinus os [CSO] to 7:00 on the tricuspid valve annulus [TVA] clock face in the left anterior oblique [LAO] projection) in nine patients undergoing atrial flutter ablation. During sinus rhythm, conduction time was measured from the CSO to the 7:00 position while pacing the CSO. Measurements were repeated after each linear lesion and after conduction block was achieved. Transisthmus conduction time at baseline, just prior to success, and after the presence of complete block was 54 +/- 9, 123 +/- 39, and 155 +/- 30 ms, respectively (P < or = 0.01). The marked delay prior to complete block resulted in reversal of the activation sequence in electrodes at TVA 7:00, creating the false appearance of isthmus block; the isthmus electrodes clearly distinguished delay from block. Catheter ablation results in progressive isthmus conduction delay prior to the creation of complete block. Electrodes spanning the isthmus and line of block are critical for distinguishing conduction delay (and pseudoisthmus block) from block.


Polyarteritis Nodosa in Pregnancy.
Polyarteritis nodosa (PAN) is a rare disease that occurs predominantly in middle-aged males; its onset during pregnancy is exceptional. We present a case of PAN with peripartum onset in a patient with a twin pregnancy after ovarian stimulation for primary infertility. The pregnancy outcome was good in terms of the children's health. In the case of the mother, however, the presence of nonspecific signs and symptoms, a noncontributory ovarian biopsy, and mimics of a puerperal infection delayed the diagnosis of PAN. The emergence of a tender subcutaneous nodule on the forearm and its histopathologic findings were diagnostic. Treatment with pulse methylprednisolone and intravenous cyclophosphamide resulted in the patient's prompt recovery. We present the case to stress the value of careful physical examination in unveiling the presence of a rare disease.


The kinetics of transdermal ethanol exchange.
The kinetics of ethanol transport from the blood to the skin surface are incompletely understood. We present a mathematical model to predict the transient exchange of ethanol across the skin while it is being absorbed from the gut and eliminated from the body. The model simulates the behavior of a commercial device that is used to estimate the blood alcohol concentration (BAC). During the elimination phase, the stratum corneum of the skin has a higher ethanol concentration than the blood. We studied the effect of varying the maximum BAC and the absorption rate from the gut on the relationship between BAC and equivalent concentration in the gas phase above the skin. The results showed that the ethanol concentration in the gas compartment always took longer to reach its maximum, had a lower maximum, and had a slower apparent elimination rate than the BAC. These effects increased as the maximum BAC increased. Our model's predictions are consistent with experimental data from the literature. We performed a sensitivity analysis (using Latin hypercube sampling) to identify and rank the importance of parameters. The analysis showed that outputs were sensitive to solubility and diffusivity within the stratum corneum, to stratum corneum thickness, and to the volume of gas in the sampling chamber above the skin. We conclude that ethanol transport through the skin is primarily governed by the washin and washout of ethanol through the stratum corneum. The dynamics can be highly variable from subject to subject because of variability in the physical properties of the stratum corneum.


Treatment of chronic infection.
Failure of an acute inflammatory response to resolve a wound infection heralds a cascade of events that affects the host and pathogens, culminating in a chronic, refractory condition. The factors contributing to this outcome include immune compromise of the host, antimicrobial resistance, wound-healing deficiencies, and the adherence of pathogens to themselves and wound surfaces via an impenetrable, resistant biofilm. To eradicate chronic infection, the pathogens, biofilm, surfaces available for adherence, and compromised tissue must be removed.


[Severity assessment of acute diarrhoea].
Clinician should recognize any life-threatening causes of diarrhoea, such as intussusceptions, surgical abdomen, and haemolytic uraemic syndrome. The following clinical features should alert: abdominal pain with tenderness, with or without guarding, pallor, jaundice, oligo-anuria, bloody diarrhoea, systemically unwell out of proportion to the level of dehydration, shock. The risk of dehydration is related to age (highest in young infants<6 months), and frequency of watery stools (>8/day) and vomiting (>2/day before 1 year and >4/day after 1 year), but these historical points have a moderate sensitivity. The severity of dehydration is rarely estimated with accuracy in terms of weight loss (third sector with full colon, absence of accurate baseline pre-dehydration weight). Combinations of examination signs perform markedly better than any individual sign in predicting dehydration (poor rate agreement, clinically unhelpful likelihood ratio). The presence of at least three signs better correlate with dehydration. Laboratory tests are not helpful. New studies are mandatory to validate severity scoring systems.


Probing ultrafast dynamics in adenine with mid-UV four-wave mixing spectroscopies.
Heterodyne-detected transient grating (TG) and two-dimensional photon echo (2DPE) spectroscopies are extended to the mid-UV spectral range in this investigation of photoinduced relaxation processes of adenine in aqueous solution. These experiments are the first to combine a new method for generating 25 fs laser pulses (at 263 nm) with the passive phase stability afforded by diffractive optics-based interferometry. We establish a set of conditions (e.g., laser power density, solute concentration) appropriate for the study of dynamics involving the neutral solute. Undesired solute photoionization is shown to take hold at higher peak powers of the laser pulses. Signatures of internal conversion and vibrational cooling dynamics are examined using TG measurements with signal-to-noise ratios as high as 350 at short delay times. In addition, 2DPE line shapes reveal correlations between excitation and emission frequencies in adenine, which reflect electronic and nuclear relaxation processes associated with particular tautomers. Overall, this study demonstrates the feasibility of techniques that will hold many advantages for the study of biomolecules whose lowest-energy electronic resonances are found in the mid-UV (e.g., DNA bases, amino acids).


Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy.
Critical illness myopathy is a disorder in which skeletal muscle becomes electrically inexcitable. We previously demonstrated that a shift in the voltage dependence of fast inactivation of sodium currents contributes to inexcitability of affected fibres in an animal model of critical illness myopathy in which denervated rat skeletal muscle is treated with corticosteroids (steroid-denervated; SD). In the current study we examined whether expression of Nav1.5 contributes to the altered voltage dependence of sodium channel inactivation in SD muscle. We used TTX and mu-conotoxin GIIIB to selectively block Nav1.4 in SD muscle and found that the level of Nav1.5 did not correlate closely with the shift in fast inactivation. Surprisingly, we found that the voltage dependence of inactivation of Nav1.4 was similar to that of Nav1.5 in skeletal muscle in vivo. In severely affected fibres, inactivation of both Nav1.4 and Nav1.5 was shifted towards hyperpolarized potentials. We examined the role of denervation and steroid treatment in the shift of the voltage dependence of inactivation and found that both denervation and steroid treatment contribute to the shift in inactivation. Our results suggest that modulation of the voltage dependence of inactivation of both Nav1.4 and Nav1.5 in vivo contributes to loss of electrical excitability in SD muscle.


Sensitive determination of (-)-epigallocatechin gallate in tea infusion using a novel ionic liquid carbon paste electrode.
This paper investigates the electrocatalytic oxidation of (-)-epigallocatechin gallate (EGCG), the main monomer flavanol found in green tea, with a novel ionic liquid, n-octylpyridinium hexafluorophosphate (OPFP) carbon paste electrode (CPE). Due to the natural viscosity and high conductivity of OPFP, this novel OPFP-CPE exhibited very attractive properties, such as high stability and electrochemical reactivity, low background current, and wide electrochemical window. Therefore, this electrode is a very good alternative to traditional chemically modified electrodes because the electrocatalytic effect can achieved without any further electrode modification. Comparative experiments were carried out using CPE and a glassy carbon electrode (GCE). With OPFP-CPE, highly reproducible and well-defined cyclic voltammograms were obtained for EGCG. Under optimal experimental conditions, the peak current of differential pulse voltammetry (DPV) response increased linearly with EGCG concentration over the range of 5.0 × 10(-7)-1.25 × 10(-5) M. The limit of detection (LOD) and the limit of quantification (LOQ) were 1.32 × 10(-7) and 4.35 × 10(-7) M, respectively. The method was applied to the determination of EGCG in green tea infusion samples, and the recovery of the spiked EGCG to the diluted (10-fold) tea extract was from 87.62 to 99.51%.


Artificial Intelligence Assessment of Renal Scarring (AIRS Study).
The goal of the Artificial Intelligence in Renal Scarring (AIRS) study is to develop machine learning tools for noninvasive quantification of kidney fibrosis from imaging scans. We conducted a retrospective analysis of patients who had one or more abdominal computed tomography (CT) scans within 6 months of a kidney biopsy. The final cohort encompassed 152 CT scans from 92 patients, which included images of 300 native kidneys and 76 transplant kidneys. Two different convolutional neural networks (slice-level and voxel-level classifiers) were tested to differentiate severe versus mild/moderate kidney fibrosis (≥50% versus <50%). Interstitial fibrosis and tubular atrophy scores from kidney biopsy reports were used as ground-truth. The two machine learning models demonstrated similar positive predictive value (0.886 versus 0.935) and accuracy (0.831 versus 0.879). In summary, machine learning algorithms are a promising noninvasive diagnostic tool to quantify kidney fibrosis from CT scans. The clinical utility of these prediction tools, in terms of avoiding renal biopsy and associated bleeding risks in patients with severe fibrosis, remains to be validated in prospective clinical trials.


[Arthroscopic meniscopexy].
The author analyses indications and therapeutic possibilities of arthroscopic meniscopexy and presents his own results assembled at the First Orthopaedic Clinic of the Masaryk University in Brno. He describes the surgical technique used, i.e. OUTSIDE-IN, in treatment of recent paracapsular ruptures of the meniscus, postoperative fixation and the rehabilitation programme. The author discusses also the necessity of a rigid plaster fixation and advocates fixation of the knee joint by a bandage as proposed by R. Jones with elimination of burdening for a period of eight weeks.


Effect of Preirradiation Fluoride Treatment on the Physical Properties of Dentin.
To determine the effects of preirradiation fluoride treatments on the Knoop hardness of dentin. Human posterior teeth mounted into acrylic resin molds were polished with silicon carbide (SiC) abrasives and 3-micron diamond paste. The Knoop hardness of dentin was measured with a Leco hardness instrument. The teeth were divided into groups of ten teeth per group as follows: no treatment (control), treatment with silver diamine fluoride (SDF), MI varnish (MI), and cavity shield (CS). The teeth were exposed to 2 Gy of daily radiation for six weeks using an X-Rad 320ix biological irradiator. Hardness was measured weekly, before, during, and after irradiation. The teeth were stored in artificial saliva at 37oC between radiation treatments. In preirradiation dentin, a Knoop hardness value of 58.8 (14.1) KHN was obtained. Treatment with SDF significantly increased KHN before irradiation. Immediately after radiation treatment, hardness was significantly reduced in all experimental groups. Postirradiation fluoride treatments increased the hardness of dentin to varying degrees. Preirradiation fluoride treatment does not provide protection from decreases in the hardness of dentin. Treatment of teeth with fluoride formulations after radiation progressively restores the hardness of dentin to different degrees.


Base-induced 1,4-elimination: insights from theory and mass spectrometry.
Experimental and theoretical studies on gas-phase base-induced 1,4-elimination reactions are summarized and discussed. The emphasis is on the synergy that is achieved by combining the complementary data from mass spectrometry and theoretical chemistry. The scope and applications of 1,4-eliminations are discussed and compared with other elementary reactions; e.g., 1,2-elimination and aliphatic (S(N)2) and allylic (S(N)2') nucleophilic substitution. Furthermore, the syn versus anti stereochemistry of 1,4-elimination reactions and the effect of E versus Z stereochemistry of the substrate are examined. Particular attention is paid to the mechanistic nature of 1,4-elimination, i.e., E2 or E1cb, as well as special features such as the single-well E2 and E1cb mechanism. Also, new results from density functional theory computations (BP86/TZ2P) are presented.


Interactions between interoception and perspective-taking: Current state of research and future directions.
Interoception, the sense of the physiological state of the body, and perspective-taking, the ability to take another's point of view, are two fundamental components contributing to our perception and interaction with the external world. However, whether the perception of our inner body influences how we perceive the external world and other people remains poorly understood. Here, we review recent behavioural and neuroimaging evidence investigating the links between dimensions of interoception (i.e., accuracy, sensibility and awareness) and perspective-taking (i.e., affective, cognitive and visual). So far, only a limited subset of these dimensions has been investigated together and the results suggest that interoceptive abilities may only interact with perspective-taking when embodied mental transformations are required. Furthermore, mainly the emotional aspects of perspective-taking are related to interoception, influencing the ability to empathise with others. Future research should systematically investigate the links between all dimensions of interoception and perspective-taking to provide full understanding of the specific role interoception has on how we perceive the world and take another's point of view.


[Expert consensus statement on Danshen Chuanxiongqin Injection in clinical practice].
Danshen Chuanxiongqin Injection is a commonly used medicine in cerebral infarction and coronary heart disease,which is recommended by many disease guidelines/consensus for cardiovascular and cerebrovascular diseases. However,there are irrational drug using in clinic,which affects the efficacy and brings safety risks. Based on clinical research evidence and expert experience,recommendations/consensus suggestion are determined through the nominal group method. The expert consensus recommends the indications,intervention time for treatment,route of drug administration,usage and dosage,course of treatment and introduces the safety in clinical application,which could provide reference for clinical use of Danshen Chuanxiongqin Injection.


A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants.
Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.


Laparoscopic Irving tubal sterilization. A case report.
Very little literature exists on the surgical management of failed tubal ligation. However, a review of the literature confirms that the failure rate of an Irving tubal sterilization is far lower than is associated with partial salpingectomy or unipolar coagulation. A laparoscopic Irving procedure was performed in a woman whose postpartum partial salpingectomy failed. To our knowledge, this is the first report of an Irving sterilization performed by laparoscopy. Laparoscopic Irving tubal sterilization can be an effective alternative to fimbriectomy or salpingectomy for failed primary tubal sterilization.


The latest on carbohydrate loading: a practical approach.
High dietary carbohydrate (CHO) intake for several days before competition (CHO loading) is known to increase muscle glycogen stores, with subsequent ergogenic performance benefits often seen in events longer than 90 min in duration. CHO-loading strategies vary in characteristics such as type and duration of dietary manipulation and the accompanying exercise/training activities. Additionally, glycogen concentration may remain elevated for up to 5 d. This versatility in CHO-loading strategies allows the athlete greater flexibility in tailoring pre-event preparation. Women who attempt to CHO load should be particularly attentive to both total energy intake and relative CHO intake; dietary CHO should exceed 8 g x kg body mass(-1) x d(-1) or 10 g x kg lean body mass(-1) x d(-1). As long as the amount ingested is adequate for loading, the type of CHO is less important, with the exception of 1-d loading protocols where the glycemic index may be an important consideration.


Untrapped: bilateral hypoplasia of the trapezius muscle.
Agenesis or congenital hypoplasia of skeletal muscles occurs infrequently but may occur with specific conditions such as Poland syndrome. The trapezius muscle can vary in the extent of its bony attachments or may have additional slips, however congenital absence or hypoplasia is extremely rare. There are only a few reports of partial or complete absence of the trapezius muscle. Two cases of bilateral absence of the trapezius were both in males and were accompanied by the absence of additional muscle in the pectoral girdle. Herein, we describe a case of a 56-year-old male cadaver with bilateral hypoplasia of the trapezius. The muscle was largely represented by atrophied muscle fibers with an abundance of fibrotic or fatty connective tissue. This subject had very minor hypoplasia of the left pectoralis major muscle, but the remaining muscles of the pectoral girdle were normal. The spinal accessory nerve terminated in the sternocleidomastoid muscle on both sides, failing to reach the trapezius. We interpret these findings to be consistent with a minor variant of Poland syndrome.


Industrial accidental deaths in the Niger delta region of Nigeria: a study of 32 autopsies in Port Harcourt.
Accidents in the oil industry in the Niger delta region of Nigera raise concerns about safety measures and the management of industrial sites. A total of 32 autopsies were performed after coroners' inquest forms were served on the authors by the State, which serve as consent and request. Standard procedures were adopted in all the cases and the reports were appropriately issued. Death from industrial accidents accounted for 2.5% and 6.1% of total autopsies and accidental death autopsies respectively. The youngest victim was a 19 year old male while the oldest was a 55 year old male. The age group 30-39 years was the most vulnerable. There was a male dominance; (male:female ratio = 9.7:1). The commonest accidents in their order of frequency were: falling from a height, explosion/fire, motor vehicle accidents and falling objects. Multiple injuries, head and neck trauma and drowning were the commonest cause of death at autopsy. Accidental deaths were commoner in the small-scale industries (81%) than in the large-scale industries (19%). This is the first time such a study has been carried out locally. The proportion of accidental deaths in the small scale industries relative to that of the large ones may be attributed to the poor enforcement of safety measures in the smaller industries


Annexin A2 promotes choroidal neovascularization by increasing vascular endothelial growth factor expression in a rat model of argon laser coagulation-induced choroidal neovascularization.
Choroidal neovascularization (CNV) is a common cause of visual loss in the elderly patients with age-related macular degeneration and represents the growth of subretinal new vessels in the macular region. This study aimed to investigate the relationship between annexin A2 (ANXA2) and vascular endothelial growth factor (VEGF) in CNV. In a rat model of argon laser coagulation-induced CNV, the mRNA expressions of the annexins and VEGF protein expression in the retina were detected using fluorescent real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. The interactions between ANXA2 and VEGF in both a retinal pigment epithelial cell line RPE-J and the rat model of CNV were examined by means of RNA interference, real-time PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA) and histopathological examinations. Fundus fluorescein angiography (FFA) showed that argon laser coagulation of the retina induced stable CNV models in the rats. Two to three weeks after the coagulation, ANXA2 and VEGF expressions in the coagulated area in the retina and choroid increased to the peak level, while the other annexin members (ANXA4, ANXA5, ANXA7 and ANXA11) showed no obvious changes. In RPE-J cells and the CNV model, RNA interference of ANXA2 gene significantly lowered the VEGF protein and mRNA expressions, and application of an adenoviral vector containing ANXA2 gene markedly increased VEGF expressions in the rat model of CNV, but produced no significant effects on the expressions of the kinase insert domain-containing receptor (KDR) or the fms-like tyrosine kinase (Flt-1). The expression of KDR inhibited the increment in ANXA2 expression, but VEGF and Flt-1 did not directly affect ANXA2 expression. Besides the role as a plasminogen and the receptor of tissue plasminogen activator, ANXA2, which is under regulation of KDR via a negative feedback mechanism, also participates in neovascularization by regulating VEGF expression through a positive feedback mechanism.


Importance of culture confirmation of shiga toxin-producing Escherichia coli infection as illustrated by outbreaks of gastroenteritis--New York and North Carolina, 2005.
Escherichia coli O157:H7 and other strains of E. coli that produce Shiga toxin are collectively known as Shiga toxin-producing E. coli (STEC). The current outbreak of STEC O157 infections associated with eating fresh spinach illustrates the importance of obtaining isolates to identify the source of the infections. Laboratory methods that do not require bacterial culture of stool specimens to identify STEC are being used increasingly by clinical diagnostic laboratories, sometimes without subsequent confirmation of a strain by isolating it in culture. This report describes findings from outbreaks of gastroenteritis in 2005 in New York and North Carolina in which clinical diagnostic laboratories initially used only non-culture methods to detect Shiga toxin (Stx). The findings highlight the importance of confirmation of Stx-positive stool specimens by bacterial culture for timely and reliable identification of STEC infections, including E. coli O157 and non-O157 STEC, to enable implementation of appropriate public health actions. An important part of that identification is determining the serotype of all STEC isolates and the subtype of STEC O157 strains so that outbreaks can be detected and traced back to sources.


Initial clinical experience with Myxo-ETlogix mitral valve repair ring.
Complexity of mitral valve repair for myxomatous disease has led to low adoption. We report initial experience with a new ring designed specifically for myxomatous disease, the Myxo-ETlogix (Edwards Lifesciences LLC, Irvine, Calif). From March 15, 2006, through November 19, 2007, 129 patients underwent mitral valve surgery for pure myxomatous disease, and 124 valves (96.1%) were repaired. The Myxo-ETlogix ring was used in 100 cases and the Physio ring (Edwards) in 24. The Myxo-ETlogix design includes a 3-dimensional shape to reduce systolic anterior motion and a larger orifice to accommodate elongated leaflets and decrease need for sliding plasty. Direct mitral valve measurements were made. Sizing was based on A2 height, and choice of ring type was based on unresected leaflet heights. There was no operative mortality or lasting perioperative morbidity. The Myxo-ETlogix group had taller A2, P1, P2, and P3 leaflet segments than the Physio group (P < or = .003). Only 1 sliding plasty was performed for asymmetry in the Myxo-ETlogix group. Predischarge and follow-up echocardiograms (n = 338 in 124 patients) disclosed transient nonobstructive chordal systolic anterior motion in 3 echocardiograms in 3 patients. No patients had 2+ or greater mitral regurgitation. At discharge, 5.7% had 1+ mitral regurgitation; this proportion was 17.3% at last follow-up (mean 6.1 +/- 4.4 months). In initial experience with the Myxo-ETlogix ring, nonobstructive systolic anterior motion has been rare and obstructive systolic anterior motion not observed. Ongoing prospective echocardiographic and clinical studies will elucidate the role of this etiology-specific ring.


Medium-term outcomes of boston type 1 keratoprosthesis implantation in Bangkok, Thailand.
The aim of this study was to investigate the medium-term outcomes after Boston type 1 keratoprosthesis surgery in patients with poor prognosis for standard keratoplasty. A prospective study of a case series was conducted at a university-based referral center from 2006 to 2013. Forty-two eyes of 40 patients with a minimum follow-up of 4 years were recruited. The main outcome measures included best spectacle-corrected visual acuity (BSCVA), keratoprosthesis retention, and complications. The mean follow-up was 64.9 ± 15.2 months (range, 48-88 months). At 1 week, 90.5% had an improvement in BSCVA by ≥2 lines compared with that in preoperative BSCVA. The best-ever vision was reached by the end of 6 months. Nevertheless, 39.5% (15/38) could not maintain the improved vision. The major etiology of visual deterioration after initial gains was glaucoma (60%). The initial keratoprosthesis retention rate was 80.9%, corresponding to a failure rate of 4 per 100 eye-years or 0.04/eye-year. Autoimmune diagnosis was the independent risk factor for keratoprosthesis failure (hazard ratio, 5.68; 95% confidence interval, 1.41-22.85; P = 0.014). The common postoperative complications were glaucoma, retroprosthetic membrane, corneal melting, infectious keratitis, and endophthalmitis. Boston type 1 keratoprosthesis is an alternative for patients who are not candidates for corneal transplants. However, there was a trend toward visual loss over time most commonly because of progressive glaucoma. Therefore, appropriate patient selection, lifelong follow-up, and early aggressive treatment of complications are recommended.


Experience and views of healthcare professionals towards people who use new psychoactive substances: Evidence from statutory, non-statutory, and private mental health and addiction healthcare services.
It is unclear how healthcare professionals (HCPs) experience and view the challenges of working with people who use New Psychoactive Substances (PWUNPS), in different healthcare services (HCS). The aim of the study was to explore HCPs' experiences of working with individuals who use NPS across statutory, non-statutory, and private mental health and addiction HCSs. HCPs completed in-depth semi-structured interviews. Audio recordings were transcribed verbatim with a mean duration of 30 min 55 s. Data were analysed through thematic analysis. A purposive sample of 14 HCPs (6 men, 8 women) with a mean age of 42.5 years were interviewed in 2019. Organisational issues, including funding, impacted the treatment for PWUNPS and HCPs perceived a lack of support dependent on their qualifications. They reported a lack of assessment, policy, harm reduction, and awareness of NPS-related symptoms including mental health problems and stigma faced by PWUNPS. HCPs need better training, education, and assessment processes to manage acute NPS intoxications and address the stigma associated with PWUNPS. There is a need for policy-making opportunities across different HCSs to ensure better healthcare outcomes for PWUNPS.


Healthcare facility benchmarking.
Development of a national healthcare facilities benchmarking program is described. As the first effort of its kind, a framework of facilities is presented. The methodology and systems used to compare measures of capital project performance are discussed. These include the development of questionnaires, databases, data mining structures, and executive dashboards. The benefits of benchmarking healthcare facilities are discussed along with several lessons learned from other, similar efforts. Future extensions of this research are discussed.


A new cembranoid from the Hainan soft coral Sinularia sp.
A new cembrane-type diterpene, diepoxycembrene A (1), has been isolated from the Hainan soft coral Sinularia sp. Its structure was elucidated on the basis of detailed analysis of its spectroscopic data, and by comparison of its NMR spectral data with those of the related model compounds.


Estimating a positive false discovery rate for variable selection in pharmacogenetic studies.
Selecting predictors to optimize the outcome prediction is an important statistical method. However, it usually ignores the false positives in the selected predictors. In this paper, we develop a positive false discovery rate (pFDR) estimate for a conventional step-wise forward variable selection procedure. We propose two views of a variable selection process, an overall and an individual test. An interesting feature of the overall test is that its power of selecting non-null predictors increases with the proportion of non-null predictors among all candidate predictors. Data analysis is illustrated with a pharmacogenetics example.


Technetium-99m-HMPAO in Tourette's syndrome on neuroleptic therapy and after withdrawal.
Both decreased and increased perfusion and metabolism have been described with PET and SPECT in different areas of the brain in patients with Gilles de la Tourette's syndrome. The aim of this study was to define the regional cerebral perfusion pattern in drug-free patients and the changes in perfusion with the usual neuroleptic treatment. A group of 13 normal control subjects and 15 unmedicated Gilles de la Tourette's syndrome patients were studied with 99mTc-HMPAO brain SPECT. Thirteen of the initial group of patients were retested on neuroleptic treatment. A semiquantitative analysis of the images was performed. Decreased perfusion in orbital and anterior medial regions of both frontal lobes as well as in both temporal lobes was observed in the nontreated group compared with control subjects. With treatment, a perfusion increase in these frontal regions and in the left medial temporal cortex was observed. Neuroleptic treatment could decrease the hyperactivity of the dopaminergic system leading to improvement of the clinical symptoms and reperfusion of some previously hypoperfused regions.


The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats.
Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson's trichrome staining method. WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.


Advances in the Understanding of the Complex Role of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension.
Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up-to-date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.


Gastrocnemius muscle architecture and achilles tendon properties influence walking distance in claudicants with peripheral arterial disease.
The extent to which gastrocnemius muscle and Achilles tendon properties contribute to the impaired walking endurance of claudicants is not known. Ultrasound images quantified muscle architecture of the lateral and medial gastrocnemius (GL and GM) and were combined with dynamometry during plantarflexor contractions to calculate tendon stress, strain, stiffness, the Young modulus, and hysteresis. Key parameters were entered into multiple regression models to explain walking endurance. Worse disease severity was significantly associated with longer fascicle: tendon length ratios (GL R = -0.789 and GM R = -0.828) and increased tendon hysteresis (R = -0.740). Walking endurance could be explained by GL and GM pennation angle, maximum tendon force, tendon hysteresis, and disease severity (R(2) = ∼0.6). Peripheral arterial disease was associated with functionally important changes in muscle and tendon properties, including the usage of stored elastic energy. Interventions known to target these characteristics should be adopted as a means to improve walking endurance.


[The incidence and significance of chronic obstructive pulmonary disease in patients with myocardial infarction and elevated st segment].
The aim of this work was to study the clinical picture and outcome of myocardial infarction in patients w'ith elevated STsegment and concomitant COPD. It involved 529 patients. Group I included 65 (12.3%) patients with previously diagnosed COPD. Group 2 was comprised of 464 (87.7%) patients without COPD. The study lasted 1 year. The patients of group 1 were older and smoked more heavily than in group 2. They had a higher clinical class of cardiac failure and more frequently showed reduced (by 40%) left ventricular ejection friction. Also, they required significantly longer hospital treatment, developed more complications, and showed higher inpatient mortality rate. The annual prognosis for them was less favourable than in group 2.


Second-order Møller-Plesset perturbation theory without basis set superposition error. II. Open-shell systems.
The basis set superposition error-free second-order Møller-Plesset perturbation theory of intermolecular interactions, based on the "chemical Hamiltonian approach," which has been introduced in Part I, is applied here to open-shell systems by using a new, effective computer realization. The results of the numerical examples considered (CH(4) em leader HO, NO em leader HF) showed again the perfect performance of the method. Striking agreement has again been found with the results of the a posteriori counterpoise correction (CP) scheme in the case of large, well-balanced basis sets, which is also in agreement with a most recent formal theoretical analysis. The difficulties of the CP correction in open-shell systems are also discussed.


Multiparameter-fluorescence activated cell sorting analysis of retroviral vector gene transfer into primitive umbilical cord blood cells.
Retroviral vector gene transfer strategies are currently being developed to treat a variety of hematopoietic disorders. To date, genetic modification of human pluripotent hematopoietic stem cells has been inefficient. In the present study we developed reagents and procedures for rapidly screening retroviral vector gene transfer conditions using a multiparameter fluorescence-activated cell sorting (FACS) assay. To identify transduced cells using FACS analysis, we developed a retroviral vector, termed MN, which stably expressed high levels of a truncated version of the low-affinity nerve growth factor receptor (LNGFR). In addition, procedures were developed for enriching CD34+ cells from cryopreserved umbilical cord blood. These cells were transduced with MN and evaluated using multiparameter FACS analysis for expression of CD34, CD38, and LNGFR. Stem cell maintenance was determined by measuring the CD34hi and CD34hiCD38lo/- cells remaining after ex vivo gene transfer. Gene transfer into these cells was measured by evaluating cells expressing high levels of LNGFR. Initial studies with this assay and with in vitro functional assays indicated that retroviral gene transfer following pre-incubation with a variety of cytokines in serum containing conditions resulted in 1) poor maintenance of hematopoietic stem cells and 2) gene transfer predominantly in relatively mature cells. When gene transfer in serum-free conditions was performed, some improvement was observed in the maintenance of cells retaining primitive immunophenotypes with no reduction in the gene transfer efficiency. The MN vector and multiparameter FACS analysis will be useful in efficiently screening ongoing efforts designed to improve stem cell gene transfer.


Conjugated bile acid replacement therapy in short bowel syndrome patients with a residual colon.
To test the efficacy of cholylsarcosine (synthetic conjugated bile acid) and ox bile extracts (mixture of natural conjugated bile acids) on fat absorption, diarrhea, and nutritional state in four short bowel syndrome (SBS) patients with a residual colon not requiring parenteral alimentation. The effect of cholylsarcosine (2 g/meal) on steatorrhea and diarrhea was examined in short-term balance studies with a constant fat intake in all four patients. The effect of continuous cholylsarcosine ingestion on nutritional state was assessed by changes in body weight in three patients. In two patients, the effects of cholylsarcosine were compared with those of ox bile extracts. Because of the low incidence rate of SBS this is not a controlled study. In balance studies, cholylsarcosine increased fat absorption from 65.5 to 94.5 g/day (a 44 % increment), an energy gain of 261 kcal/d. Fecal weight increased by 26 %. In two patients natural conjugated bile acids also reduced steatorrhea, but greatly increased diarrhea. As outpatients consuming an unrestricted diet and ingesting cholylsarcosine, three patients gained weight at an average rate of 0.9 kg/week without worsening of diarrheal symptoms. Cholylsarcosine is efficacious and safe for enhancing fat absorption and nutritional status in short bowel syndrome patients with residual colon. Natural conjugated bile acids improve steatorrhea to a smaller extent and greatly worsen diarrhea.


Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies.
Hematologic malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biological studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematologic malignancies.


Semiparametric regression analysis of failure time data with dependent interval censoring.
Interval-censored failure-time data arise when subjects are examined or observed periodically such that the failure time of interest is not examined exactly but only known to be bracketed between two adjacent observation times. The commonly used approaches assume that the examination times and the failure time are independent or conditionally independent given covariates. In many practical applications, patients who are already in poor health or have a weak immune system before treatment usually tend to visit physicians more often after treatment than those with better health or immune system. In this situation, the visiting rate is positively correlated with the risk of failure due to the health status, which results in dependent interval-censored data. While some measurable factors affecting health status such as age, gender, and physical symptom can be included in the covariates, some health-related latent variables cannot be observed or measured. To deal with dependent interval censoring involving unobserved latent variable, we characterize the visiting/examination process as recurrent event process and propose a joint frailty model to account for the association of the failure time and visiting process. A shared gamma frailty is incorporated into the Cox model and proportional intensity model for the failure time and visiting process, respectively, in a multiplicative way. We propose a semiparametric maximum likelihood approach for estimating model parameters and show the asymptotic properties, including consistency and weak convergence. Extensive simulation studies are conducted and a data set of bladder cancer is analyzed for illustrative purposes. Copyright © 2017 John Wiley & Sons, Ltd.


Contact Tracing for an Imported Case of Crimean-Congo Hemorrhagic Fever - Experience from a Tertiary Care Center in Kerala, South India.
A 30-year-old male working in an abattoir in UAE returned home to Kerala, South India, after getting diagnosed with Crimean-Congo hemorrhagic fever infection. He was admitted to a tertiary care center on the day of arrival and was placed under isolation. Due to the risk of spread of infection among health-care workers, contact-tracing and symptom-monitoring activities were undertaken. As strict standard contact precautions, isolation, contact identification and listing, quarantine, and sensitization of health-care workers were implemented, no secondary cases occurred.


Late-Onset MS: Disease Course and Safety-Efficacy of DMTS.
Multiple sclerosis (MS), an inflammatory demyelinating and neurodegenerative disease of the central nervous system, usually begins between the ages of 20 and 49 years, though in rare cases it is diagnosed in childhood and adolescence before the age of 18 years, or at the age of 50 years and later. When the onset of the disease occurs at 50 years or older it is conventionally defined as late onset MS (LOMS). Compared to classical MS, the LOMS is characterized by progressive course, a greater delay in diagnosis and a higher prevalence of motor disability. The older the patients, the greater is the risk of comorbidities that can negatively influence the course of the disease and can limit therapeutic strategies. To date, there is no study focused on the efficacy of Disease Modifying Therapies (DMT) in older patients with MS. The only data available are retrievable from subgroup analysis from phase-3 trials of DMT efficacy. In this work, we discuss how the aging process influences the onset, the clinical course and the therapeutic approach in LOMS.


Comparison of aminolysis of 2-pyridyl and 4-pyridyl x-substituted benzoates in acetonitrile: evidence for a concerted mechanism involving a cyclic transition state.
A kinetic study on reactions of 2-pyridyl X-substituted benzoates (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Brønsted-type plots are linear with βnuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that ΔH(‡) increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS(‡) remains nearly constant with a large negative value. The constant TΔS(‡) value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.


Binding of Stimuli-Responsive Ruthenium Aqua Complexes with 9-Ethylguanine.
Stimuli-responsive ruthenium complexes proximal- and distal-[Ru(C10tpy)(C10pyqu) OH2]2+ (proximal-1 and distal-1; C10tpy = 4'-decyloxy-2,2':6',2″-terpyridine and C10pyqu = 2-[2'-(6'-decyloxy)-pyridyl]quinoline) were experimentally studied for adduct formation with a model DNA base. At 303 K, proximal-1 exhibited 1:1 adduct formation with 9-ethylguanine (9-EtG) to yield proximal-[Ru(C10tpy)(C10pyqu)(9-EtG)]2+ (proximal-RuEtG). Rotation of the guanine ligand on the ruthenium center was sterically hindered by the presence of an adjacent quinoline moiety at 303 K. Results from 1H NMR measurements indicated that photoirradiation of a proximal-RuEtG solution caused photoisomerization to distal-RuEtG, whereas heating of proximal-RuEtG caused ligand substitution to proximal-1. The distal isomer of the aqua complex, distal-1, was observed to slowly revert to proximal-1 at 303 K. In the presence of 9-EtG, distal-1 underwent thermal back-isomerization to proximal-1 and adduct formation to distal-RuEtG. Kinetic analysis of 1H NMR measurements showed that adduct formation between proximal-1 and 9-EtG was 8-fold faster than that between distal-1 and 9-EtG. This difference may be attributed to intramolecular hydrogen bonding and steric repulsion between the aqua ligand and the pendant moiety of the bidentate ligand..


Detection of negative ions from individual ultrafine particles.
Aerosol mass spectrometers can be used to classify individual airborne particles on the basis of chemical composition. While positive ion mass spectra are normally used to characterize ultrafine particles (defined here as particles smaller than 200 nm in diameter), negative ion mass spectra can provide complementary information. To effectively utilize the negative ion mass spectra of ultrafine particles, it is important to understand biases in the formation and detection of negative ions. It is found that the intensity of negative ions is generally less than that of positive ions, due to the creation of electrons in the ablation process that must react to form negative ions. The ablation efficiency, defined as the probability that an ablated particle produces a detectable ion signal, exhibits both size and composition dependencies. The ablation efficiency for detection of negative ions follows the same trends as the ablation efficiency for the detection of positive ions: sodium chloride and ammonium nitrate have higher ablation efficiencies than oleic acid, and the ablation efficiency decreases with the particle diameter. The ablation efficiency of negative ions is less than or equal to the ablation efficiency of positive ions, and the relative difference increases as the particle diameter decreases. Pure ammonium sulfate particles exhibit an ablation efficiency too low to be measured in the present experiments. However, trace amounts of sulfate in mixed-composition particles can be readily detected in the negative ion mass spectra.


Aqua-[1-(4-carb-oxy-phen-yl)-1H-imidazole-κN](pyridine-2,6-dicarboxyl-ato-κO,N,O)copper(II) monohydrate.
In the title complex, [Cu(C(7)H(3)NO(4))(C(10)H(8)N(2)O(2))(H(2)O)]·H(2)O, the Cu(II) ion is in a slightly distorted square-pyramidal geometry. Two carboxyl-ate O atoms and one pyridine N atom from a pyridine-2,6-dicarboxyl-ate ligand chelate the Cu(II) ion, forming two stable five-membered metalla rings. One imidazole N atom from a 1-(4-carb-oxy-phen-yl)imidazole ligand and one water mol-ecule complete the five-coordination. O-H⋯O hydrogen bonds involving the coordinated water mol-ecules and carboxyl-ate groups link the complex mol-ecules into chain-containing dinuclear macrocycles. O-H⋯O hydrogen bonds involving the uncoordinated water mol-ecules link the chains into a layer extending parallel to (10[Formula: see text]).


9-Benzylidene-naphtho[2,3-b]thiophen-4-ones as novel antimicrotubule agents-synthesis, antiproliferative activity, and inhibition of tubulin polymerization.
A novel series of 9-benzylidene-naphtho[2,3-b]thiophen-4-ones and structurally related compounds were synthesized and evaluated for their ability to inhibit tubulin polymerization. The 4-hydroxy-3,5-dimethoxy-benzylidene analogue 15d was identified as a potent cytotoxic agent in an assay based on K562 leukemia cells. Antiproliferative activity of 15d and the 2,4-dimethoxy-3-hydroxy-benzylidene analogue 15e was additionally evaluated against a panel of 12 tumor cell lines, including multidrug resistant phenotypes. All resistant cell lines were sensitive to these compounds. Concentration-dependent flow cytometric studies showed that K562 cells as well as KB/HeLa cells treated by 15d were arrested in the G2/M phases of the cell cycle. Moreover, four compounds strongly inhibited tubulin polymerization with activities higher or comparable to those of the reference compounds. In competition experiments, the most active compounds strongly displaced radiolabeled colchicine from its binding site in the tubulin, showing IC50 values virtually 3- to 4-fold lower than that of colchicine.


Sympathetic nervous activity in patients with acute coronary syndrome: a comparative study of inflammatory biomarkers.
Previous studies have shown that both sympathetic hyperactivity and enhanced inflammatory responses are associated with poor outcomes in patients with acute coronary syndrome (ACS). Whether there is a correlation between these two characteristics remains unclear. Thirty-four patients with uncomplicated ACS were evaluated; their mean age was 51.7±7.0 years, 79.4% were male, and 94.1% had myocardial infarction (MI). On the fourth day of hospitalization, they underwent muscle sympathetic nerve activity (MSNA) analysis (microneurography), as well as ultrasensitive C-reactive protein (usCRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity measurements. These evaluations were repeated at 1, 3, and 6 months after hospitalization. Both MSNA and inflammatory biomarkers were elevated during the acute phase of ACS and then decreased over time. At hospitalization, the median usCRP level was 17.75 (IQR 8.57; 40.15) mg/l, the median IL-6 level was 6.65 (IQR 4.45; 8.20), the mean Lp-PLA2 activity level was 185.8 ±52.2 nmol/min per ml, and mean MSNA was 64.2±19.3 bursts/100 heart beats. All of these variables decreased significantly over 6 months compared with the in-hospital levels. MSNA was independently associated with the peak level of creatine kinase isoenzyme MB (CKMB) in the acute phase (P=0.027) and with left ventricular ejection fraction (LVEF) at 6 months (P=0.026). Despite the increased levels of inflammatory biomarkers and sympathetic hyperactivity in the initial phase of ACS, no significant correlations between them were observed in any of the analyzed phases. Our data suggest that although both sympathetic hyperactivity and inflammation are concomitantly present during the early phase of ACS, these characteristics manifest via distinct pathological pathways.


Evaluation of Ica Gene in Comparison with Phenotypic Methods for Detection of Biofilm Production by Coagulase Negative Staphylococci in a Tertiary Care Hospital.
Biofilm producing bacteria are responsible for several chronic infections and are difficult to treat as they show much greater resistance to antibiotics. The major virulence factor determining the pathogenicity of CoNS has now well defined and found to be biofilm production. The study was conducted to isolate and characterize Coagulase Negative Staphylococci (CoNS) and their ability to form biofilms was evaluated by phenotypic and genotypic methods. A total of 96 clinical isolates of CoNS were characterized and subjected to biofilm detection by tissue culture plate method (TCP), tube method (TM), congo red agar method (CRA) and PCR. Staphylococcus epidermidis was the most commonly isolated species 76(79.17%). The ica gene was present in 35 (36.45%) of CoNS isolates which were detected as biofilm producers by TCP. Biofilm producing isolates showed higher antibiotic resistance(72.1%). Majority of biofilm producers had strong association with medical device related infections. To compare PCR based dectection method for presence of ica genes with TCP, the test share the specific identification rates. The sensitivity and specificity of TCP method in detection of biofilm was high in comparison with TM and CRA. TCP can be recommended as a general screening test for biofilm detection.


Occurrence of fungi and cytotoxicity of the species: Aspergillus ochraceus, Aspergillus niger and Aspergillus flavus isolated from the air of hospital wards.
The basic care requirement for patients with weakened immune systems is to create the environment where the risk of mycosis is reduced to a minimum. Between 2007 and 2013 air samples were collected from various wards of a number of hospitals in Kraków, Poland, by means of the collision method using MAS-100 Iso MH Microbial Air Sampler (Merck Millipore, Germany). The air mycobiota contained several species of fungi, and almost 1/3 of it was made up of the species of the Aspergillus genus. Sixty-one strains of species other than A. fumigatus were selected for the research purposes, namely: 28 strains of A. ochraceus, 22 strains of A. niger and 11 strains of A. flavus species. Selected fungi underwent a cytotoxicity evaluation with the application of the MTT colorimetric assay (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide). The assay assesses cell viability by means of reducing the yellow tetrazolium salt to insoluble formazan. A semi-quantitative scale for cytotoxicity grading was adopted: low cytotoxic effect (+) with half maximal inhibitory concentration (IC50) for values ranging from 31.251 cm2/ml to 7.813 cm2/ml, medium cytotoxic effect (++) for values ranging from 3.906 cm2/ml to 0.977 cm2/ml and the high one (+++) for values ranging from 0.488 cm2/ml to 0.061 cm2/ml. The absence of cytotoxicity was determined when the IC50 values was at ≥ 50. For 48 samples the analyzed fungi displayed the cytotoxic effect with A. ochraceus in 26 out of 28 cases, with 11 strains displaying the high cytotoxic effect. The lowest cytotoxicity was displayed by fungi of A. niger in 13 out of 22 cases, and the major fungi of A. flavus species were toxic (9 out of 11 cases). A half of the fungi displayed the low cytotoxic effect. On the basis of the comparison of average cytotoxicity levels it was determined that there were significant differences in the levels of cytotoxicity of the analyzed fungi. However, such statement may not provide grounds for a definite conclusion about the compared species of fungi that display a more cytotoxic effect than others. Int J Occup Med Environ Health 2017;30(2):231-239.


Uncertainties on predicted concentrations of radionuclides in terrestrial foods and ingestion doses.
Models are routinely used to calculate doses following routine releases and potential accidental releases of radionuclides. These models contain a number of parameters. Values for many of these are not accurately known. The primary aim of this study was to determine the level of uncertainty on predicted concentrations of radionuclides in foods, and doses to individuals consuming those foods, arising from uncertainties on the model input parameter values. A secondary objective was to identify those input parameters whose uncertainty makes a major contribution to the overall uncertainty on the predicted endpoints. The methodology adopted and results obtained are presented for the following radionuclides: 90Sr, 131I, 137Cs and 239Pu. The estimated uncertainty ratios (the ratio of the 95th to the 5th percentile) are frequently very large, often two to three orders of magnitude. The results of this study may be used to identify areas where further research could improve assessment capabilities.