Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae.
Kojic acid is produced in large amounts by Aspergillus oryzae as a secondary metabolite and is widely used in the cosmetic industry. Glucose can be converted to kojic acid, perhaps by only a few steps, but no genes for the conversion have thus far been revealed. Using a DNA microarray, gene expression profiles under three pairs of conditions significantly affecting kojic acid production were compared. All genes were ranked using an index parameter reflecting both high amounts of transcription and a high induction ratio under producing conditions. After disruption of nine candidate genes selected from the top of the list, two genes of unknown function were found to be responsible for kojic acid biosynthesis, one having an oxidoreductase motif and the other a transporter motif. These two genes are closely associated in the genome, showing typical characteristics of genes involved in secondary metabolism.


A time motion study of community mental health workers in rural India.
Community Health Workers (CHWs) are critical to providing healthcare services in countries such as India which face a severe shortage of skilled healthcare personnel especially in rural areas. The aim of this study is to understand the work flow of CHWs in a rural Community Mental Health Project (CMHP) in India and identify inefficiencies which impede their service delivery. This will aid in formulating a targeted policy approach, improving efficiency and supporting appropriate work allocation as the roles and responsibilities of the CHWs evolve. A continuous observation Time Motion study was conducted on Community Health Workers selected through purposive sampling. The CHWs were observed for the duration of an entire working day (9 am- 3 pm) for 5 days each, staggered during a period of 1 month. The 14 different activities performed by the CHWs were identified and the time duration was recorded. Activities were then classified as value added, non-value added but necessary and non-value-added to determine their time allocation. Home visits occupied the CHWs for the maximum number of hours followed by Documentation, and Traveling. Documentation, Administrative work and Review of work process are the non-value-added but necessary activities which consumed a significant proportion of their time. The CHWs spent approximately 40% of their time on value added, 58.5% of their time on non-value added but necessary and 1.5% of their time on non-value added activities. The CHWs worked for 0.7 h beyond the stipulated time daily. The CHW's are "dedicated" mental health workers as opposed to being "generalists" and their activities involve a significant investment of their time due to the specialized nature of the services offered such as counselling, screening and home visits. The CHWs are stretched beyond their standard work hours. Non-value added but necessary activities consumed a significant proportion of their time at the expense of value-added activities. Work flow redesign and implementation of Health Management Information Systems (HMIS) can mitigate inefficiencies.


The Assessment of Reconstructive Urology-Associated Google Search Trends During COVID-19.
To demonstrate public interest in reconstructive urology during the COVID-19 pandemic by using Google Trends (GT). The study was conducted between August 1 and August 11, 2021. A total of 18 terms related to reconstructive urology were determined. Public interest in all terms were evaluated with the GT application using the filters 'worldwide', 'all categories', and 'web search'. To determine public interest in reconstructive urology during the COVID-19 pandemic, three 12-week periods following the declaration of COVID-19 (March 11 to June 4, 2020, June 5 to August 29, 2020, and August 30 to November 23, 2020) were compared with the same periods in the past four years (2016-2019). Comparisons of March 11 to June 4, 2020, and the same days in the previous four years revealed that total public attention to reconstructive urology significantly declined (-16.2%, p=0.035). In the comparison of the second 12-week duration (June 5 to August 29, 2020, vsJune 5 to August 29, 2016-2019), only the bladder augmentation term had significantly lower search frequency during COVID-19 (-46.3%, p=0.043), but buried penis (50.3%, p=0.001), urinary incontinence (15.3%, p=0.001), and stress urinary incontinence (21.7%, p=0.001) keywords had significantly higher inquiries. The comparison of the third 12-week period searches for only urinary incontinence significantly increased (p=0.001). Present study showed that public interest in reconstructive urology significantly reduced in the first 12 weeks after COVID-19 was declared a pandemic. However, public attention to reconstructive urology reached similar levels after 12 weeks from the beginning of COVID-19. Additionally, the term urinary incontinence was searched statistically more frequently during the COVID-19.


Field additivity of Stiles's Pi-4 color mechanism.
Stiles's middle-wave color mechanism Pi-4 is field additive for mixtures of 410-, 480-, 530-, 622-, and 670-nm adaptation fields, when studied with a 1-deg, 200-msec, 500-nm foveal test flash at 10 times absolute threshold.


An instrument to collect data on frequency and intensity of symptoms in older palliative cancer patients: A development and validation study.
To develop and validate an instrument to collect data on symptoms (frequency/intensity) in older palliative cancer patients. A four-phase instrument development and validation study was performed. A preliminary version of the instrument was developed through a literature review. Face- and content validity were assessed in a Delphi-procedure with eleven experts. Cognitive interviewing with 24 older cancer patients was performed to enhance content validity of the instrument. Test-retest was performed to assess the stability. An 40-item instrument was developed. The Assessment Symptoms Palliative Elderly (ASPE) collects data on frequency and intensity of 24 physical, 10 psychological, 3 functional, 1 spiritual and 2 social symptoms. Content validity was excellent (I-CVI 81.8%-100.0% and S-CVI 92.9%). Cognitive interviewing allowed to improve the content validity. Test-retest showed substantial to almost perfect agreement for 87.5% of the items. No item had poor or fair agreement. This study resulted in the development of the ASPE which reflects good properties for face- and content validity and reliability. Cognitive interviewing has a valuable contribution in the validation process. The instrument can be used to gain insight in symptoms in older palliative cancer patients.


Prodrugs. Do they have advantages in clinical practice?
Prodrugs are pharmacologically inactive chemical derivatives of a drug molecule that require a transformation within the body in order to release the active drug. They are designed to overcome pharmaceutical and/or pharmacokinetically based problems associated with the parent drug molecule that would otherwise limit the clinical usefulness of the drug. The scientific rationale, based on clinical, pharmaceutical and chemical experience, for the design of various currently used prodrugs is presented in this review. The examples presented are by no means comprehensive, but are representative of the different ways in which the prodrug approach has been used to enhance the clinical efficacy of various drug molecules.


Interleukin-1 beta increases activity of human endothelial progenitor cells: involvement of PI3K-Akt signaling pathway.
Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine upregulated in acute phase of heart ischemic disease. Controversial effects of IL-1β have been demonstrated on endothelial progenitor cells (EPCs) functional activity. The aim of this study was to investigate the in vitro effect of IL-1β on activity of human origin EPCs and the possible mechanism involved. EPCs were isolated from peripheral blood of healthy volunteers without cardiovascular risk factors and characterized. After ex vivo cultivation, EPCs were stimulated with a series of final concentrations (0, 0.1, 1, and 10 ng/ml) of IL-1β for 24 h. In some other experiments, EPCs were pretreated with 10 μM LY294002 (Akt inhibitor) for 30 min and then stimulated with 1 ng/ml IL-1β for 24 h. Cell proliferation, apoptosis, adhesion, and migration were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V/propidium iodide binding assay, adhesion assay, and transwell migration assay. In addition, the vascular endothelial vascular growth factor-A (VEGF-A) production has been examined using quantitative real-time RT-PCR and ELISA assay. Furthermore, the total and phosphorylation level of Akt was determined by Western blot. IL-1β significantly stimulated EPC proliferation, migration, and adhesion and upregulated the angiogenic growth factor VEGF-A at mRNA and protein level, while exerted no influence on cell apoptosis. However, pretreatment with LY294002 significantly diminished IL-1β-induced proliferation, migration, adhesion, and VEGF-A production. One nanogram per milliliter IL-1β for 15 min activated phosphorylation of Akt. These results suggest a potent role for IL-1β in upregulating EPCs functions. The phosphatidyl-inositol-3-kinase-Akt signaling pathway could be involved in the regulation of EPCs functions induced by IL-1β.


cis-Nitromethylene neonicotinoids as new nicotinic family: synthesis, structural diversity, and insecticidal evaluation of hexahydroimidazo[1,2-alpha]pyridine.
A series of neonicotinoids analogues of hexahydroimidazo[1,2-alpha]pyridine were modified at 5-, 6-, and 7-positions, and their insecticidal activities were evaluated. Introducing a methyl or ethyl at 7-position increased the insecticidal activities, while other substituents decreased activities. When alkyl substituents were introduced to 7-position, the insecticidal activities against Pea aphids decreased in the order methyl (7a)>ethyl (7b)>n-butyl (7e)>phenyl (7f)>n-propyl (7c)>iso-propyl (7d), p-NO(2)-phenyl (7g). Modifications at 5-, 6- or both at 6- and 7-positions with methyl or ethyl were unfavorable to activities. Interestingly, introducing methyl to 7-position not only increased insecticidal activities against pea aphids, but also show higher insecticidal activities than imidacloprid against imidacloprid-resistant brown planthopper.


Plasma-generated reactive water mist for disinfection of N95 respirators laden with MS2 and T4 bacteriophage viruses.
Due to the shortage of personal protective equipment (PPE) during the COVID-19 pandemic, the interest and demand for sterilization devices to reuse PPE has increased. For reuse of face masks, they must be effectively decontaminated of potential infectious agents without compromising its filtration ability during sterilization. In this study, we utilized an atmospheric pressure pulsed dielectric barrier discharge (DBD), combined with nebulized liquid microdroplets to generate plasma-activated mist (PAM). MS2 and T4 bacteriophages were used to conduct the decontamination tests on two types of N95 respirators. Results showed at least a 2-log reduction of MS2 and T4 on N95 respirators treated in one cycle with 7.8% hydrogen peroxide PAM and at least a 3-log reduction treated in 10% hydrogen peroxide PAM. In addition, it was found that there was no significant degradation in filtration efficiency of N95 respirators (3M 1860 and 1804) treated in 10% hydrogen peroxide PAM found after 20 cycles. In terms of re-useability of masks after treatment as determined, it was shown that the elastic straps of 3M 1804 were fragmented after 20 treatment cycles rendering them unusable, while the straps of 3M 1860 were not negatively affected even after 20 disinfection cycles.


Reaggregation behavior of different types of collagen in vitro: variations in the occurrence and structure of dimeric segment long-spacing collagen.
Segment long-spacing collagen (SLS) can be precipitated from solutions of collagen using ATP as the inducing agent. Dimeric SLS aggregates have been observed in addition to monomeric SLS. We have compared collagen types I, II, III, and V with respect to their ability to form dimeric SLS in vitro. These collagen types were isolated from bovine tissues and characterized by polyacrylamide slab gel electrophoresis of the respective alpha-chains. Only monomeric SLS can be detected in preparations of collagen types I and III. Dimeric SLS, on the other hand, accounts for the majority of the crystallites seen in preparations of collagen types II and V. Dimeric SLS from both collagen types II and V reveal overlap zones at the carboxy-terminal ends of the collagen molecules. However, dimeric SLS from collagen types II and V differ with respect to their overlap distances. Significant portions of the triple helical domains of collagen molecules are occupied by the overlap region of dimeric SLS from type II collagen. On the other hand, dimeric SLS from type V collagen is composed of molecules overlapping only at their short nonhelical telopeptides. It is concluded that the ability of collagen molecules to aggregate into dimeric SLS under defined experimental conditions is collagen type dependent.


In vitro bioactivity of Bioroot™ RCS, via A4 mouse pulpal stem cells.
To evaluate the biocompatibility and osteoinductive properties of Bioroot™ RCS (BR, Septodont, France) compared to Kerr's Pulp Canal Sealer™ (PCS, Kerr, Italy) using the mouse pulp-derived stem cell line A4, which have an osteo/odontogenic potential in vitro and contribute to efficient bone repair in vivo. A4 cells were cultured at the stem cell stage in the presence of solid disks of BR or PCS, whereas untreated A4 cells were used as control. After 3, 7, 10 days of direct contact with the sealers, cell viability was quantified using Trypan Blue exclusion assay. Immunolabelings were performed to assess the expression of odontoblast markers i.e. type 1 collagen, DMP1 or BSP. Finally, sealer-treated cells were induced toward osteo/odontogenic differentiation to assess the impact of the sealers on mineralization by Von Kossa staining. Statistical significance was evaluated by one-way analysis of variance and t-test (p<0.05). BR did not alter the viability and morphology of A4 pulpal cells compared to control group (p>0.05); however, living cell percentage of PCS was significantly lower compared to control and BR groups (p<0.05). BR preserved the intrinsic ability of A4 cells to express type 1 collagen, DMP1 or BSP at the stem cell stage. It did not alter the integrity of collagen fibers surrounding the cells and promoted overexpression of BSP and DMP1 at the cell surface. In contrast to PCS, BR did not compromise the mineralization potential of pulpal A4 stem cells. Bioroot™ RCS was not as cytotoxic as PCS. It did not recruit the pulpal stem cells toward differentiation but preserve their osteo-odontogenic intrinsic properties. Bioroot™ RCS might provide more suitable environment to induce stem cells for hard tissue deposition.


Delusional infestation. The interface of delusions and hallucinations.
Delusional infestation represents a unique subtype of the delusional disorder category. This article presents the phenomenology, etiology, and treatment of delusional infestation. This article also reviews historical and theoretical attempts to distinguish tactile sensory phenomena as either hallucinations or delusions.


Rare renal pseudotumor associated with chronic glomerulonephritis mimicking renal cell carcinoma.
We describe a unique case of chronic glomerulonephritis that simulated a renal neoplasm observed on abnormal imaging. Histologic examination of the resected specimen supported the assumption that the observed mass lesion resulted from regional sparing in the development of chronic glomerulonephritis. We believe this case is the first to show the etiology of pseudotumor as an extremely uncommon manifestation of chronic glomerulonephritis by histologic examination.


Mysticism and schizophrenia: A phenomenological exploration of the structure of consciousness in the schizophrenia spectrum disorders.
Mysticism and schizophrenia are different categories of human existence and experience. Nonetheless, they exhibit important phenomenological affinities, which, however, remain largely unaddressed. In this study, we explore structural analogies between key features of mysticism and major clinical-phenomenological aspects of the schizophrenia spectrum disorders-i.e. attitudes, the nature of experience, and the 'other', mystical or psychotic reality. Not only do these features gravitate around the issue of the basic dimensions of consciousness, they crucially seem to implicate and presuppose a specific alteration of the very structure of consciousness. This finding has bearings for the understanding of consciousness and its psychopathological distortions.


On the invariability of the total-to-peak ratio in gamma-ray spectrometry.
It is demonstrated that the assumption on the independence of the total-to-peak ratio of the source position in gamma-ray spectrometry holds for coaxial detectors with sufficient accuracy to make it applicable to the determination of the full energy peak efficiencies in environmental measurements via the so-called efficiency transfer method. The calculations show that for planar detectors the assumption breaks down at higher gamma-ray energies and that for such detectors the use of the efficiency transfer method is only warranted for gamma-ray energies up to 200 keV.


Surgical hospital audit of record keeping (SHARK)--a new audit tool for the improvement in surgical record keeping.
Accurate and legible record keeping is a crucial part of good medical practice. Surgical Hospital Audit of Record Keeping (SHARK) is a new audit and teaching tool for junior doctors. The author has designed the tool, based on the Royal College of Surgeons guidelines, to anonymously score the different surgical teams' medical records within a hospital. It takes into account regular record keeping during ward rounds, together with the operation note and admission clerking. The SHARK audit tool assesses 45 individual areas within surgical records. Fifteen points are apportioned for an initial surgical clerking, 13 for a subsequent record entry, and 17 for the operation note to give an overall score out of 45. It was implemented at 2 hospitals and used to educate medical students. The results were poor and improved with education at both sites. There was 80% total agreement with a κ coefficient for interobserver reliability of 0.6. This study shows that the SHARK tool is simple to use, repeatable, and reliable in improving record keeping.


Immobilisation of quantum dots by bio-orthogonal PCR amplification and labelling for direct gene detection and quantitation.
A sensitive and versatile detection scheme based on quantum dot immobilisation on a solid support through bio-orthogonal PCR amplification and labelling has been developed for detection and quantification of gene targets in complex DNA mixtures.


Pre-exposure studies with purified chick embryo cell culture rabies vaccine and human diploid cell vaccine: serological and clinical responses in man.
Clinical reactions and neutralizing antibody responses to six pre-exposure regimens of purified chick embryo cell culture rabies vaccine (PCECV) and human diploid cell strain rabies vaccine (HDCSV) were studied in 177 volunteers. Antibody kinetics, height of the response and persistence of antibody over two years were virtually identical after PCECV and HDCSV. An antibody response was detected in all subjects on day 14 when the highest titres were found after two intramuscular (i.m.) 1.0 ml doses of a schedule of immunization on days 0, 7 and 21. In comparison, a schedule of immunization on days 0, 28 and 56 ultimately evoked the highest titres 21 days after the final injection, but antibody persisted equally well over two years with either schedule. Neutralizing antibody titres were lower after intradermal (i.d.) vaccination with 0.1 ml compared to 1.0 ml i.m. on days 0, 7 and 21, but when given on days 0, 28 and 56 the responses were comparable. Three subjects with a personal or family history of atopy developed urticarial lesions after PCECV. Both vaccines were otherwise well tolerated.


Hypothalamus volume mediates the association between adverse childhood experience and PTSD development after adulthood trauma.
The hypothalamus is critical for regulation of the hypothalamic-pituitary-adrenal (HPA) axis and response to stress. Adverse childhood experience (ACE) can affect brain structure, which may contribute to development of posttraumatic stress disorder (PTSD) after subsequent adult trauma. It is unclear, however, if ACE history is particularly associated with aspects of hypothalamic structure which contribute to development of PTSD. To address this issue, the present study longitudinally assessed hypothalamic volumes and their associations with ACE and early post-trauma stress symptoms in subjects who did or did not develop PTSD during 12 months after adult trauma. 109 subjects (18-60 years, F/M = 75/34) completed the PTSD Checklist (PCL) questionnaire for post-trauma stress symptoms, the Childhood Trauma Questionnaire (CTQ) for ACE assessment, and an initial MRI brain scan for hypothalamic volume measurement, within 2 weeks after adult trauma. At post-trauma 12 months, subjects underwent a subsequent PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS), and a follow-up MRI scan. Left and right hypothalamus volumes at 2 weeks after adult trauma negatively correlated with CTQ scores. Right hypothalamus volume at this early time mediated an association between ACE and PTSD symptoms 12 months later. Right hypothalamus volumes also remained persistently smaller from 2 weeks to 12 months after trauma in survivors who developed PTSD. These results suggest that smaller right hypothalamus volume may be related to ACE history in ways that contribute to PTSD development after trauma in adulthood.


Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.
To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).


Residency, migration and a compromise: Adaptations to nest-site scarcity and food specialization in three fennoscandian owl species.
Fennoscandian owl species differ, among other things, with respect to nest-site, food, clutch size, mate and territory fidelity, sexual size dimorphism and longevity. All these life characteristics help shaping the pattern of mobility and wintering strategies found in owl species, but it seems justifiable to regard food abundance and nest-site availability as the most prominent ones.The Ural owl is a generalist feeder and nests in tree cavities which are scarce. The pair is faithful to their territory for life. The long-eared owl is a vole specialist, breeds in secondhand twig-nests, which are abundantly available, and is largely migratory. Tengmalm's owl is a vole specialist and breeds in tree holes. As an adaptation to the conflicting pressures of periodical food scarcity and of keen competition for the nest holes which therefore have better be guarded uninterruptedly this species has evolved a strategy of partial migration, adult males being resident and females and young being migratory.


Effect of pulse frequency and amplitude of D-Trp6-luteinizing hormone-releasing hormone on the pulsatile secretion of prolactin and LH.
This work analyzes the effect of the pulse amplitude and frequency of a potent LHRH analog, D-Trp6-LHRH, in a perfusion system of isolated rat pituitary cells. To this purpose, we studied the LH and PRL secretion in different conditions: basal secretion, secretion after increasing concentrations of D-Trp6-LHRL (0.001, 0.01, 0.1 and 1 nM) secretion in function of the pulses frequency (2,3, and 4 pulses per h) and amplitude (0.1, 1 and 10 nM). The principal findings were: 1. The basal LH and PRL secretions was pulsatile; 2. The stimulation of LH by the analog was not dose-dependent; 3. When more than 2 pulses per h were administered, a rapid desensitization of gonadotroph to release LH (at 20-30 min) occurred; 4. There was a loss of pulsatility of PRL secretion with an increase in the pulse frequency and amplitude of the D-Trp6-LHRH, which was produced parallelly to the desensitization of the gonadotroph to release LH. In summary, these findings suggest that a rapid loss of pulsatility of the PRL when the D-Trp6-LHRH pulse frequency and amplitude is increased might be due to the early desensitization of the gonadotroph to the analog.


Muscle necrosis by N-methylated p-phenylenediamines in rats: structure-activity relationships and correlation with free-radical production in vitro.
Certain derivatives of p-phenylenediamine have been shown to cause necrosis of cardiac and skeletal muscle in rats; in vitro, such compounds are known to autoxidize to the corresponding radical cations, with concomitant formation of oxygen free-radicals. In the present study, the autoxidation rates of p-phenylenediamine and its N-methyl, dimethyl, trimethyl and tetramethyl derivatives have been determined and compared with the severity of the muscle necrosis induced by each of these compounds in rats. A close correlation was observed between autoxidation rate in vitro and toxicity in vivo, suggesting that free-radical species may be involved in the initiation of the muscle damage caused by these substances.


Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction.
The aim of the present study is the definition of a brief structured interview (SI) providing scores useful for identification and quantification of pathogenetic factors of erectile dysfunction (ED). A SI was developed and applied to a consecutive series of 320 ED patients. A 13-item SI, with three-factor analysis-derived scales, was identified and applied for validation to an independent consecutive series of 194 ED patients. PGE(1) (10 microg) intracavernosal injection, penile duplex ultrasound (PDU), blood hormones, PSA, glycemia, and lipids were used for the assessment of an organic component (OC), and Middlesex Hospital Questionnaire (MHQ) modified for psychological disturbances. Scale 1, dealing with OC, showed a positive correlation with age, BMI, blood pressure, glycemia, and inverse correlation, with testosterone, PGE(1) and several parameters derived from PDU. Scale 2, related to partner's relationship, was not correlated with organic parameters. Scale 3, which measures psychopathological traits was correlated with MHQ scales. Scale 1 (>3) had a sensitivity of 67.9% and a specificity of 67.6% for OC. SIEDY((c)) provides information on ED pathogenesis and might assist physicians in diagnostic and therapeutic choices.


c-myc mRNA overexpression is associated with lymph node metastasis in colorectal cancer.
To elucidate the relationship between oncogene overexpression and malignant potential of colorectal cancer, the expression of three genes, c-myc, c-fos and c-Ki-ras was examined. Northern blot hybridisation was performed on fresh tissues excised from 35 patients with primary colorectal cancer. Overexpression of c-myc mRNA was evident in 25 of the patients (71%). Tumours with c-myc overexpression had a significantly higher frequency of lymph node metastasis than did those without (68 versus 20%, P < 0.05). The survival rate tended to be poorer (P = 0.06) in patients with c-myc overexpression (79% for 3 years) than in those without it (100%). We found no significant relationship between overexpression of the other two genes and pathological features. These findings suggest that c-myc overexpression is one parameter which can be used to determine the malignant potential of colorectal cancer.


Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC.
Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n = 396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7-68.6 %] and 79.5 % [95 % CI, 75.3-83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0-136 m). For patients transplanted upfront and in multivariate analysis, age (HR = 2 [1.2-3.4], p = .01, and HR = 2.3 [1.2-4.5], p = .01), disease status at time of ASCT (HR = 1.7 [1.1-2.6], p = .01 and HR = 1.8 [1.1-3.1], p = .03), and use of rituximab (HR = 0.5 [0.3-0.8], p = .002 and HR = 0.5 [0.3-0.9], p = .01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.


Epoxy-annulations by reactions of alpha-amido ketones with vinyl sulfonium salts. Reagent versus substrate control and kinetic resolution.
Diphenyl vinyl sulfonium salt and chiral amido-ketones undergo highly diastereoselective epoxy-annulation reactions in good yield. The use of a chiral vinyl sulfonium salt dominates the stereochemical outcome of the annulation reaction (reagent control is greater than substrate control), and this has allowed the kinetic resolution of racemic amido-ketones to be achieved.


Long-Chain Acyl Carnitines Aggravate Polystyrene Nanoplastics-Induced Atherosclerosis by Upregulating MARCO.
Exposure to micro- and nanoplastics (MNPs) is common because of their omnipresence in environment. Recent studies have revealed that MNPs may cause atherosclerosis, but the underlying mechanism remains unclear. To address this bottleneck, ApoE-/- mice are exposed to 2.5-250 mg kg-1 polystyrene nanoplastics (PS-NPs, 50 nm) by oral gavage with a high-fat diet for 19 weeks. It is found that PS-NPs in blood and aorta of mouse exacerbate the artery stiffness and promote atherosclerotic plaque formation. PS-NPs activate phagocytosis of M1-macrophage in the aorta, manifesting as upregulation of macrophage receptor with collagenous structure (MARCO). Moreover, PS-NPs disrupt lipid metabolism and increase long-chain acyl carnitines (LCACs). LCAC accumulation is attributed to the PS-NP-inhibited hepatic carnitine palmitoyltransferase 2. PS-NPs, as well as LCACs alone, aggravate lipid accumulation via upregulating MARCO in the oxidized low-density lipoprotein-activated foam cells. Finally, synergistic effects of PS-NPs and LCACs on increasing total cholesterol in foam cells are found. Overall, this study indicates that LCACs aggravate PS-NP-induced atherosclerosis by upregulating MARCO. This study offers new insight into the mechanisms underlying MNP-induced cardiovascular toxicity, and highlights the combined effects of MNPs with endogenous metabolites on the cardiovascular system, which warrant further study.


Tissue engineering in dermatology - from lab to market.
Tissue Engineering is a branch of regenerative medical technology which helps replace damaged tissue using appropriate scaffolding, living cells, and growth factors. Using tissue engineering products can be a promising method for treating skin lesions such as wounds and deep burns. The interaction and interconnection of cells within the bio-culture medium or within a three-dimensional scaffold provides the conditions for tissue regeneration and subsequent healing of skin wounds. Tissue engineering in the field of dermatology has evolved over time from a single application of skin cells or biopolymer scaffolds to the use of cell and scaffold combinations for the treatment, repair, and closure of acute and chronic skin wounds. It has evolved. This technology has reached a point where most products are accepted, and the body rejects a small number, which strengthens the tissue engineering market. In this article, we aimed to review and study the market of this field by reviewing various articles on tissue engineering in the field of dermatology. Tissue-engineered skin substitutes are future options for wound healing and tissue regeneration strategies.


Stones in orthotopic, non-obstructing ureteroceles.
A case is presented in which stones were found bilaterally in orthotopic, non-obstructing ureteroceles in a child. This is apparently the first reported instance of this condition occurring in the presence of sterile urine. A review of related literature gives clues to the possible etiology of such an occurrence.


Carotid Compliance and Parahippocampal and Hippocampal Volume over a 20-Year Period.
We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study. We included participants with common carotid compliance measurements at visit 1 (1987-1989) and volumetric brain MRI at visit 5 (2011-2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume. Of the 614 participants, higher compliance was correlated with higher PHV (R = 0.218[0.144-0.291], p < 0.001) and HV (R = 0.181 [0.105-0.255, p < 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia (p < 0.001 and p < 0.001, respectively). Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline.


Rotating edge-field driven processing of chiral spin textures in racetrack devices.
Topologically distinct magnetic structures like skyrmions, domain walls, and the uniformly magnetized state have multiple applications in logic devices, sensors, and as bits of information. One of the most promising concepts for applying these bits is the racetrack architecture controlled by electric currents or magnetic driving fields. In state-of-the-art racetracks, these fields or currents are applied to the whole circuit. Here, we employ micromagnetic and atomistic simulations to establish a concept for racetrack memories free of global driving forces. Surprisingly, we realize that mixed sequences of topologically distinct objects can be created and propagated over far distances exclusively by local rotation of magnetization at the sample boundaries. We reveal the dependence between chirality of the rotation and the direction of propagation and define the phase space where the proposed procedure can be realized. The advantages of this approach are the exclusion of high current and field densities as well as its compatibility with an energy-efficient three-dimensional design.


Complications and the Need for Long-Term Follow-Up after Secondary Speech Surgery: A National and Longitudinal Claims Analysis.
Although most patients attain normal speech after cleft palate repair, up to 20 percent require secondary speech surgery. Despite the frequency of these procedures, complications and rates of subsequent revisions of secondary speech surgery after all procedure types have never been reviewed using national, longitudinal data. The authors examined insurance claims from Clinformatics Data Mart between 2001 and 2017. Cases were categorized as palatalprocedures (i.e., palatoplasty, revision palatoplasty, secondary lengthening, palatal island flap) or pharyngeal procedures (i.e., pharyngeal flap, dynamic sphincter pharyngoplasty) (n = 846). Continuous enrollment from 180 days before to 30 days after surgery was required. Patients were excluded if they underwent palatoplasty, or any surgery at less than 3 years of age, without a speech diagnosis. Outcomes included 30-day complications and rates of subsequent revision secondary speech surgery. Multivariable logistic regression was used to evaluate the relationship between procedure type and complications. In this cohort, 52.5 percent underwent pharyngeal procedures, and 47.5 percent underwent palatal procedures. Complications occurred in 10.9 percent of patients and included respiratory complications (4.0 percent), bleeding (1.2 percent), dehiscence (3.6 percent), and critical care episodes (3.0 percent). There was no difference in complications between procedure types (OR, 0.87; 95 percent CI, 0.56 to 1.37; p = 0.56). The subsequent revision rate was 12.7 percent, but was 21.7 percent in patients with 3 years of postoperative enrollment. Although complication rates were comparable to those in recent literature, rates of subsequent revisions of secondary speech procedures were high in patients with longer postoperative enrollment. Thus, these patients merit prolonged follow-up, as velopharyngeal dysfunction may recur over time. Therapeutic, III.


Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain.
In this paper, we show that recombinant human lactoferrin (rhLF) has been stably expressed at 0.5% brown rice flour weight for nine generations. Process development indicates that rhLF can be efficiently extracted from rice flour in 20 mM phosphate buffer (pH 7.0) containing up to 0.5 M NaCl and at a ratio of 1 kg flour to 10 L buffer. After solid/liquid separation, the extract can then be loaded directly onto an ion-exchange column and rhLF can be eluted using 0.8 M NaCl. The resulting rhLF is about 95% pure. A range of biochemical and biophysical analyses were carried out and results indicated that the purified rhLF was identical to its native human counterpart other than its glycosylation. Economic analysis shows that at 600 kg/year scale, the cash cost to produce 1 g of rhLF of pharmaceutical grade is US$ 5.90. Analysis also indicates that the expression level has profound impact on costs related to planting, milling, extraction and purification, thus high level expression of recombinant protein in plants is one of the key parameters for the success of plant made pharmaceuticals.


Alveolar Ridge Preservation Procedures Performed with a Freeze-Dried Bone Allograft: Histologic Outcomes in a Cohort Study.
The primary aim of this study was to assess the histomorphometric outcomes of extraction sockets grafted with freeze-dried bone allograft (FDBA) and sealed with a collagen membrane after 3 months of healing in specific region of interest (ROI) areas. The secondary aims were to analyze the biomaterial resorption rate, the bone-to-biomaterial contact (BBC), and the area and perimeter of grafted particles compared with commercially available FDBA particles. Fifteen patients underwent tooth extractions and ridge preservation procedures performed with FDBA and a collagen membrane. Bone biopsy samples were harvested after 3 months at the time of implant placement for histologic and histomorphometric analysis. Two areas of concern (ROI1 and ROI2) with different histologic features were identified within the biopsy samples; ROI1, ROI2, and commercially available particles were analyzed and compared. The following parameters were analyzed: newly formed bone, marrow space, residual graft particles, perimeter and area of FDBA particles, and BBC. The histomorphometric analysis showed 35.22% ± 10.79% newly formed bone, 52.55% ± 16.06% marrow spaces, and 12.41% ± 7.87% residual graft particles. Moreover, the histologic data from ROI1 and ROI2 showed that (1) the mean percentage of BBC was 64.61% ± 27.14%; (2) the newly formed bone was significantly higher in ROI1 than in ROI2; (3) the marrow space was significantly lower in ROI1 than in ROI2; and (4) the FDBA particles in ROI1 sites showed significantly lower area and perimeter when compared to commercially available FDBA particles. This latter data led to the hypothesis that FDBA particles embedded in newly formed bone undergo a resorption/remodeling process.


The effects of low dose (less than 1 rad) X-rays on the erythropoietic marrow.
Adult female Sprague-Dawley rats were exposed (200 kvp X-rays) to whole body doses of 22-1320 mrad and examined for changes in the level of red blood cell precursors (RBCp) in the marrow at 5-30 weeks post-irradiation, under nonbled and phlebotomy-induced anemic stress conditions. Increases in the RBCp %, RBCp/mg marrow, and RBCp/skeleton under nonbled conditions, and a suppressed erythroid response to an induced anemia, were found after acute doses in the range of at least 70 mrad. Dosages of 22 or 44 mrad that induced no measurable changes when applied only once were found to be effective when they were employed 4 or 2 times/week, respectively. The results suggested the presence of a linear-quadratic dose-response relationship in which the quadratic function exists between 88 and 981 mrad, and the linear dependency, below 88 mrad.


Apoptosis detected in the amygdala following myocardial infarction in the rat.
Myocardial infarction (MI) contains a risk factor for developing episodes of Major Depressive Disorder (MDD). Apoptosis is commonly observed in the reperfused myocardial infarcted heart, and recent findings suggest the existence of apoptosis in MDD. Cytokines, which are released by ischemic myocardium and which may induce apoptosis, have been proposed as a possible cause for MDD. Myocardial infarction was produced in anesthetized rats by a 40-minute occlusion of the left anterior descending coronary artery followed by 72 hours of reperfusion. Determination of apoptosis was done in the amygdala, hippocampus and vermis of MI and Sham rats treated or not with pentoxyfilline (PTX), a cytokine synthesis inhibitor (10 mg/kg/day intraperitoneal). Compared to Sham rats, the amygdala of MI rats showed significantly reduced P13K activity, increased Bax/Bcl-2 ratio, caspase-3 activity, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. The effect of MI on apoptosis was completely reversed in presence of PTX. No statistical difference was observed in the hippocampus and the vermis in the different groups for any of the biochemical measurements. These results indicated that MI induce apoptosis in amygdala by a cytokine-sensitive mechanism and may explain the MDD observed following myocardial infarction.


Divergent marijuana trajectories among men: Socioeconomic, relationship, and life satisfaction outcomes in the mid-30s.
Given recent changes in marijuana policy in the United States, it is important to understand the long-term effects of marijuana use on adult functioning. We examined whether men who displayed different trajectories of marijuana use from adolescence through emerging adulthood (age ∼15-26) differed in terms of socioeconomic, social, and life satisfaction outcomes in their mid-30s. Data came from a longitudinal sample of men who were recruited in early adolescence (N=506) and followed into adulthood. Four trajectory groups based on patterns of marijuana use from adolescence into emerging adulthood were compared on adult outcomes (age ∼36) before and after controlling for co-occurring use of other substances and several pre-existing confounding factors in early adolescence. The potential moderating effect of race was also examined. Although there were initially group differences across all domains, once pre-existing confounds and co-occurring other substance use were included in the model, groups only differed in terms of partner and friend marijuana use. Chronic marijuana users reported the highest proportions of both. Frequent and persistent marijuana use was associated with lower socioeconomic status (SES) for Black men only. After statistically accounting for confounding variables, chronic marijuana users were not at a heightened risk for maladjustment in adulthood except for lower SES among Black men. Chronic users were more likely to have friends and partners who also used marijuana. Future studies should take into account pre-existing differences when examining outcomes of marijuana use.


Signaling pathways of interleukin-1 actions in the brain: anatomical distribution of phospho-ERK1/2 in the brain of rat treated systemically with interleukin-1beta.
Interleukin-1beta is released at the periphery during infection and acts on the nervous system to induce fever, neuroendocrine activation, and behavioral changes. These effects are mediated by brain type I IL-1 receptors. In vitro studies have shown the ability of interleukin-1beta to activate mitogen-activated protein kinase signaling pathways including p38, c-Jun N-terminal kinase and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In contrast to other mitogen-activated protein kinases, little is known about ERK1/2 activation in the rat brain in response to interleukin-1beta. The aim of the present study was therefore to investigate spatial and temporal activation of ERK1/2 in the rat brain after peripheral administration of interleukin-1beta using immunohistochemistry to detect the phosphorylated form of the kinase. In non-stimulated conditions, phosphorylated ERK1/2 immunoreactivity was observed in neurons throughout the brain. Administration of interleukin-1beta (60 microg/kg, i.p.) induced the phosphorylation of ERK1/2 in areas at the interface between brain and blood or cerebrospinal fluid: meninges, circumventricular organs, endothelial like cells of the blood vessels, and in brain nuclei involved in behavioral depression, fever and neuroendocrine activation: paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala and arcuate nucleus. Double labeling of phosphorylated ERK1/2 and cell markers revealed the expression of phosphorylated ERK1/2 in neurons, astrocytes and microglia. Since phosphorylated ERK1/2 was found in structures in which type I IL-1 receptor has already been identified as well as in structures lacking this receptor, activation of ERK1/2 is likely to occur in response to both direct and indirect action of interleukin-1beta on its target cells.


Impact of the occlusal contact pattern and occlusal adjustment on the wear and stability of crowns.
To investigate the impact of the occlusal contact situation and occlusal adjustment on wear, roughness, and fracture force of molar crowns. CAD/CAM crowns (lower right first molar, n = 64; 4 groups à 8, 3Y-TZP zirconia and resin composite) and corresponding antagonists (upper right first molar; 3Y-TZP zirconia) were manufactured. Crowns were constructed according to two principles of occlusion (group "T": Peter K. Thomas' "point-centric" cusp-to-fossa tripodization concept, with 15 contact points; group "RA" Sigurd P. Ramfjord and Major M. Ash, "freedom in centric" concept with four contacts). On one half of the crowns, occlusal adjustment was performed (groups "T adjusted" and "RA adjusted"). All crowns underwent combined thermal cycling (TC) and mechanical loading (ML) (ML: 1.2 × 106 cycles, 50 N, 2 Hz, mouth opening 1 mm; TC: 2 × 3000 cycles, 5/55°C). Wear area and depth of each contact point on the occlusal surfaces of crowns and antagonists were determined using a digital microscope. Surface roughness (Ra, Rz) was measured in and besides (reference) the worn area (3D laser-scanning microscope). Fracture force of the crowns was determined (statistics: Levene-test, one-way-ANOVA; Bonferroni-post-hoc-test; between-subjects effects, Pearson correlation, α=0.05). The resin composite crowns yielded significantly higher mean values for wear area and depth (p < 0.001) and lower fracture forces (p < 0.001). Resin composite surfaces showed increased roughness after TCML while zirconia exhibited smoothened surfaces. The occlusal design significantly impacted wear depth (p = 0.012) and fracture force (p < 0.001). Resin composite crowns with fewer contact points (group RA) showed more wear and lower fracture force. Adjusted resin composite crowns showed increased wear areas and depths (p = 0.009-0.013). For zirconia crowns, the adjustment impacted wear area (p = 0.013), wear depth (p = 0.008), and fracture force (p = 0.006), with adjusted zirconia crowns exhibiting more wear and lower maximum forces until fracture. Zirconia wear depth was also impacted by the occlusal design (p = 0.012). Antagonistic wear was influenced by the restorative material, the occlusal contact pattern, and the adjustment. The investigated materials show strongly varying performances with zirconia being significantly influenced by the adjustment, while for resin composites, contact design and adjustment had a major impact. The results show the necessity of adapting occlusal design and adjustment in order to improve roughness, wear, and stability of zirconia and resin composite crowns.


Self-esteem of adolescent females as related to race, economic status, and area of residence.
The Rosenberg Self-esteem Scale was used to measure the self-esteem of 109 14- and 16-yr.-old (+/- 6 mo.) girls. The self-esteem scores were categorized by economic status, race, and area of residence. For urban girls mean self-esteem of upper economic status subjects was significantly higher than that of those at the lower economic status. The self-esteem of upper economic status urban girls was significantly higher than the self-esteem of their rural peers. Finally, the self-esteem of the urban black girls was significantly higher than the self-esteem of the urban white girls.


Structure of an OhrR-ohrA operator complex reveals the DNA binding mechanism of the MarR family.
The mechanisms by which Bacillus subtilis OhrR, a member of the MarR family of transcription regulators, binds the ohrA operator and is induced by oxidation of its lone cysteine residue by organic hydroperoxides to sulphenic acid are unknown. Here, we describe the crystal structures of reduced OhrR and an OhrR-ohrA operator complex. To bind DNA, OhrR employs a chimeric winged helix-turn-helix DNA binding motif, which is composed of extended eukaryotic-like wings, prokaryotic helix-turn-helix motifs, and helix-helix elements. The reactivity of the peroxide-sensing cysteine is not modulated by proximal basic residues but largely by the positive dipole of helix alpha1. Induction originates from the alleviation of intersubunit steric clash between the sulphenic acid moieties of the oxidized sensor cysteines and nearby tyrosines and methionines. The structure of the OhrR-ohrA operator complex reveals the DNA binding mechanism of the entire MarR family and suggests a common inducer binding pocket.


Timely manner application of hand orthoses to patients with amyotrophic lateral sclerosis: A case report.
In patients with amyotrophic lateral sclerosis, the atrophy of hand muscles often causes impairment of thumb/finger motion and disabilities in their activities of daily living. Hand orthoses are effective for such impairment and disabilities; however, there are some difficulties in their application. In this case report, we present the timely application of hand orthoses and introduce our clinical algorithm for the application of hand orthoses to patients with amyotrophic lateral sclerosis. Our clinical algorithm was applied to 11 patients. The numbers of applications and the durations of the use of orthoses were as follows: 4, web spacer; 4, short thumb spica; 8, long thumb spica; and 2, cock-up splint; and 2.75, 2.0, 0.63, and 2.0 months, respectively. The clinical algorithm for the application of hand orthoses is helpful in choosing the optimal orthoses and contributes to maximizing patients' function, independence, and quality of life. Hand orthoses are useful for improving the activities of daily living of patients with amyotrophic lateral sclerosis. The clinical algorithm might be helpful for many physicians in choosing the optimal orthoses in a timely manner.


Cervical osteochondroma (C2 level) with vertebral artery occlusion and second cervical nerve root irritation.
A case of osteochondroma arising from the C2 transverse process, responsible for vertebral artery compression with complete occlusion and C2 nerve root irritation with C2 neuralgia, is reported. Complete surgical removal was achieved via the lateral anterior approach.


Investigation of continuous-batch mode of two-stage culture of Nannochloropsis sp. for lipid production.
Microalgal lipid induction through nitrogen stress often suffers from a contradiction between biomass productivity and lipid content, i.e., either high biomass productivity with low lipid content or vice versa. A two-stage nitrogen-replete and nitrogen-deplete (NR-ND) culture was suggested to be an option to attain high lipid productivity. In this study, the effects of culture conditions and modes on biomass productivity and lipid productivity of Nannochloropsis sp. in the two stages were comprehensively investigated. The optimal culture conditions for the two stages, aiming to high biomass productivity and lipid productivity respectively, were consistent, i.e., CO2 content in aeration (1 %), phosphorus concentration in medium (181 μmol/L), incident light intensity (150 μE/(m(2)s)), temperature (25 °C). Different culture modes of the two stages were compared. The overall lipid productivity of the two-stage continuous-batch mode achieved 0.123 g/(L day), which was 60.3, 48.2, 34.9 and 13.5 % higher than that of single nitrogen-replete batch, single nitrogen-limited batch, continuous nitrogen-replete culture and two-stage batch-batch culture, respectively, and also higher than most reported values. This contribution provides fundamental data for the two-stage NR-ND cultivation process design of Nannochloropsis sp.


How feedback loops between meso- and macrofauna and organic residues contrasting in chemical quality determine decomposition dynamics in soils.
The concept of feedback loops between changes in chemical quality of decomposing organic residues and changes in faunal communities was employed in studying how such feedback loops, representing distinct ecological successional stages, determine decomposition dynamics in soils. A 52-week litterbag decomposition study was superimposed onto an 18-year long term field experiment. Four types of organic residues contrasting in chemical quality (i.e., nitrogen (N), lignin, polyphenols, cellulose) were incorporated into soil annually to assess decomposition and associated meso- and macrofauna communities. In the first 4 weeks after residue incorporation (loop #1), the abundances (densities) of both mesofauna and macrofauna were positively influenced by labile cellulose and N. The mesofauna Collembola and Acari contributed 70-100% and 0-30% to the decomposition, respectively, while the macrofauna beetles and flies contributed 20-90% and 10-66%, respectively. The abundances were highest under groundnut (high N, low lignin) ([1.35 and 0.85 individual number (g dry litter)-1] for mesofauna and macrofauna, respectively). The presence of macrofauna at week 2 led to a mass loss (R2 = 0.67**), indicating that macrofauna preceded mesofauna in degrading residue. In week 8 (transition of loop #2 to #3), only macrofauna (beetles dominated contributing 65%) played an important role in lignin decomposition (R2 = 0.56**), resulting in a mass loss (R2 = 0.52**). In week 52 (loop #4) macrofauna, ants (Formicidae) replaced beetles as the dominant decomposers showing a feedback reaction to availability of protected cellulose. The Formicidans contributed 94% to the decomposition and influenced losses of mass (R2 = 0.36*) and N (R2 = 0.78***). The feedback loop concept provides a more comprehensive "two-sided" view into decomposition, as regulated simultaneously by two factors, than earlier "one-sided" approaches to soil fauna-mediated decomposition.


CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves.
The velocity of nerve conduction is moderately enhanced by larger axonal diameters and potently sped up by myelination of axons. Myelination thus allows rapid impulse propagation with reduced axonal diameters; however, no myelin-dependent mechanism has been reported that restricts radial growth of axons. By label-free proteomics, STED-microscopy and cryo-immuno electron-microscopy we here identify CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) as a myelin protein specifically localized to the Schwann cell membrane exposed to the axon. We find that disruption of Cmtm6-expression in Schwann cells causes a substantial increase of axonal diameters but does not impair myelin biogenesis, radial sorting or integrity of axons. Increased axonal diameters correlate with accelerated sensory nerve conduction and sensory responses and perturbed motor performance. These data show that Schwann cells utilize CMTM6 to restrict the radial growth of axons, which optimizes nerve function.


Synthetic Biology Provides a Toehold in the Fight against Zika.
The World Health Organization has identified the development of a rapid point-of-care diagnostic test for Zika virus as a top research priority. In a recent Cell paper, Pardee et al. (2016) have exploited recent advances in synthetic biology and molecular engineering to deliver a sensitive, affordable, and field-ready Zika test.


Halogenated metabolites from Japanese Laurencia spp.
Further investigation of Laurencia species from Japanese waters, which were collected at three locations, yielded brominated metabolites, a labdane- type diterpene and a C15 acetogenin possessing a terminal bromoallene group. Their structures were deduced from analysis of spectroscopic data.


Two tightly linked genes coding for NAD-dependent malic enzyme and dynamin-related protein are associated with resistance to Cercospora leaf spot disease in cowpea (Vigna unguiculata (L.) Walp.).
Cercospora leaf spot (CLS) caused by Cercospora canescens is an important disease of cowpea (Vigna unguiculata). A previous study using an F2 population [CSR12906 (susceptible) × IT90K-59-120 (resistant)] identified a major QTL qCLS9.1 for resistance to CLS. In this study, we finely mapped and identified candidate genes of qCLS9.1 using an F3:4 population of 699 individuals derived from two F2:3 individuals segregating at qCLS9.1 from the original population. Fine mapping narrowed down the qCLS9.1 for the resistance to a 60.6-Kb region on cowpea chromosome 10. There were two annotated genes in the 60.6-Kb region; Vigun10g019300 coding for NAD-dependent malic enzyme 1 (NAD-ME1) and Vigun10g019400 coding for dynamin-related protein 1C (DRP1C). DNA sequence analysis revealed 12 and 2 single nucleotide polymorphisms (SNPs) in the coding sequence (CDS) and the 5' untranslated region and TATA boxes of Vigun10g019300 and Vigun10g019400, respectively. Three SNPs caused amino acid changes in NAD-ME1 in CSR12906, N299S, S488N and S544N. Protein prediction analysis suggested that S488N of CSR12906 may have a deleterious effect on the function of NAD-ME1. Gene expression analysis demonstrated that IT90K-59-120 and CSR12906 challenged with C. canescens showed different expression in both Vigun10g019300 and Vigun10g019400. Taken together, these results indicated that Vigun10g019300 and Vigun10g019400 are the candidate genes for CLS resistance in the cowpea IT90K-59-120. Two derived cleaved amplified polymorphic sequence markers were developed to detect the resistance alleles at Vigun10g019300 and Vigun10g019400 in IT90K-59-120.


Back to the drawing board. Hospitals, insurer support not enough to save California's universal coverage plan; lack of physician backing hurt chances.
A defeat in California for Gov. Arnold Schwarzenegger's comprehensive healthcare reform plan was not only a blow to advocates of the initiative but also could be a setback for other states that were hoping to follow in the Golden State's footsteps. Lloyd Dean, left, president and CEO of Catholic Healthcare West, said that he is "concerned this lack of progress will result in further deterioration of California's healthcare system".


Surgical resection of a rare primary retroperitoneal mucinous borderline tumor of Müllerian Origin: A case report.
•Primary retroperitoneal mucinous tumors (PRMTs) are a rare group of cystic neoplasms consisting of three subtypes.•PRMTs are histologically similar to ovarian mucinous tumors but lack true ovarian tissue.•PRMTs should be considered in the differential diagnosis when encountering retroperitoneal cystic lesions.•During surgical resection tumor disruption should be avoided.•Surgical resection alone provides durable disease control for mucinous borderline tumors of low malignant potential.


Long-term outcome of complete cardiovascular implantable electronic device removal with cardiopulmonary bypass.
Definitive endovascular techniques have been developed for pacemaker lead extraction; however, a few patients require immediate secondary open heart surgery because of incomplete transvenous lead extraction. This study examined the safety, effectiveness, and long-term outcome of the removal of cardiovascular implantable electronic device (CIED) via median sternotomy under cardiopulmonary bypass. The removal of CIED was performed in 6 patients (mean age 57 ± 16 years, 5 males and 1 female), from September 2000 to April 2011. The reasons for removal included eradication of an infection in 5 patients and elimination of pacemaker component allergy in 1. Positive culture results, including methicillin-sensitive Staphylococcus aureus (MSSA, n = 2), methicillin-resistant S. aureus (MRSA, n = 1), coagulase-negative staphylococci (CNS, n = 1), and methicillin-resistant S. epidermidis (MRSE, n = 1) were observed in all 5 infected patients. Mitral annuloplasty (n = 1), mitral valvuloplasty (n = 1), tricuspid annuloplasty (n = 3). Implantation of myocardial pacing leads (n = 5) were performed concomitantly (n = 4), or secondarily (n = 1). All 6 patients were alive in good condition at 72 ± 55 months following CIED removal. New device infection occurred in 1 patient during long-term follow up. Complete surgical removal of pacing systems via median sternotomy with cardiopulmonary bypass is, therefore, considered to be safe and feasible with acceptable long term results.


Adaptive servo-ventilation: How does it fit into the treatment of central sleep apnoea syndrome? Expert opinions.
The preliminary results of the SERVE-HF study have led to the release of safety information with subsequent contraindication to the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnoeas in patients with chronic symptomatic systolic heart failure with left ventricular ejection fraction (LVEF) ≤ 45%. The aim of this article is to review these results, and to provide more detailed arguments based on data from the literature advocating the continued use of ASV in different indications, including heart failure with preserved LVEF, complex sleep apnoea syndrome, opioid-induced central sleep apnea syndrome, idiopathic central SAS, and central SAS due to a stroke. Based on these findings, we propose to set up registers dedicated to patients in whom ASV has been stopped and in the context of the next setting up of ASV in these specific indications to ensure patient safety and allow reasoned decisions on the use of ASV.


Status of lung transplantation.
Selected patients with terminal lung disease have been managed effectively by lung transplantation. Strict selection criteria for donors and recipients, attention to technical detail, and avoidance of perioperative corticosteroids increase the likelihood of success. The underlying pulmonary disease determines the appropriate procedure. Single-lung transplantation is most appropriate for patients with pulmonary fibrosis. Patients with emphysema or septic pulmonary disease who have adequate or recoverable cardiac function can be well served by double-lung transplantation. However, such patients are still treated in some centers by combined heart-lung transplantation. Patients with right-heart failure secondary to vascular or parenchymal pulmonary disease are best managed by combined heart-lung transplantation. Donor availability, airway healing, and diagnosis of rejection remain significant problems and are the focus of experimental and clinical investigation in many centers.


Thyroid Dysfunction in Patients with Pulmonary Artery Hypertension (PAH): The Effect of Therapies Affecting the Prostanoid Pathway.
Epoprostenol, a synthetic prostaglandin I2 (PGI2) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another synthetic prostaglandin analog, and selexipag, an oral selective Inositol Phosphate (IP) prostacyclin receptor agonist, have also been approved for treatment of PAH. Prostacyclin and its analogs cause a variety of side effects in patients with PAH; however, thyroid dysfunction is rarely reported. After treating an index case of thyroid dysfunction occurring after initiation of epoprostenol, we reviewed our databases of PAH patients treated with epoprostenol, treprostinil or selexipag to identify the occurrence of this association. We identified six cases of thyroid dysfunction in our cohort: five after initiation of an intravenous prostacyclin (epoprostenol) and one after initiation of an oral prostacyclin receptor agonist (selexipag). Four of the patients presented with hyperthyroidism and two with a large autoimmune goiter. Graves' disease was seen in three patients, Hashimoto's disease in two patients and thyrotoxicosis in one patient. Therapy with medications targeting the prostacyclin pathway is a potential risk factor for the development of symptomatic thyroid disease.


Does aging have an impact on hemoglobin? Study in elderly population at rural teaching hospital.
The prevalence of anemia increases with age. Some serious underlying conditions may lead to anemia in the old age. The present study was undertaken to detect and do morphological typing of anemia and further delineate etiological factors in elderly patients. In this hospital-based prevalence study carried out a tertiary care center over one and half years, a total of 90 patients were fully evaluated for etiology and typing of anemia in elderly (>60 years age) patients. Details of other significant medical and surgical history were noted. Laboratory investigations were conducted, which included complete hemogram, peripheral blood smear, reticulocyte count, erythrocyte sedimentation rate estimation, serum urea, serum creatinine and serum lactate dehydrogenase, bone marrow examination (with Prussian blue marrow iron staining), serum iron and serum total iron-binding capacity, serum ferritin, and stool and urine examination. The mean hemoglobin as per age was 60-64 years- 5.95 gm%, 65-69 years - 6.7 gm%, 70-74 years - 6.58 gm%, and 75-79 years - 6.87 gm%. The difference not being significant (p = 0.33). Morphologically, 53 patients (24 males and 29 females) had microcytic anemia, 27 (17 males and 10 females) had normocytic anemia, and 10 (8 males and 2 females) had macrocytic anemia. Anemia of chronic disease (ACD) was the most common occurrence (50, 55.56%), followed by iron deficiency anemia (IDA) (27, 30%), macrocytic anemia (9, 10%), and others 4 (4.44%). The cause of anemia was found in 10 out of 27 (37.03%) patients in the IDA group, 28 out of 50 (56%) in the ACD group, whereas the etiology was discernible in only one out of nine cases (11.1%) of macrocytic anemias. There was no significant difference observed in the mean hemoglobin levels as the age increased. Morphologically, the majority of the patients had microcytic anemia, followed by normocytic anemia. A population-based study is recommended for further assessment of the prevalence and causes of anemias in asymptomatic elderly subjects.


A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. II. Strongly Correlated MCSCF Wave Functions.
A methodology is developed for the quantitative identification of the quasi-atomic orbitals that are embedded in a strongly correlated molecular wave function. The wave function is presumed to be generated from configurations in an internal orbital space whose dimension is equal to (or slightly larger) than that of the molecular minimal basis set. The quasi-atomic orbitals are found to have large overlaps with corresponding orbitals on the free atoms. They separate into bonding and nonbonding orbitals. From the bonding quasi-atomic orbitals, localized bonding and antibonding molecular orbitals are formed. The resolution of molecular density matrices in terms of these orbitals furnishes a basis for analyzing the interatomic bonding patterns in molecules and the changes in these bonding patterns along reaction paths. A new bond strength measure, the kinetic bond order, is introduced.


No mutagenicity and oral toxicity of winter mushroom powder treated with atmospheric non-thermal plasma.
This study aimed to evaluate the mutagenicity and oral acute toxicity of winter mushroom powder (PW) treated by atmospheric non-thermal plasma (ANP). Winter mushroom powder without plasma treatment (CW) containing an equivalent amount of sodium nitrite as PW was used as a control. The Ames test revealed that the number of revertant colonies did not significantly increase compared to that in the control. Acute toxicity was assessed in rats that were fed a single dose of winter mushroom powder (5000 mg/kg body weight). Results of the acute toxicity test revealed no remarkable clinical symptoms in any of the rats. No significant difference was observed in of the serum biochemical parameters between the treatments. Regardless of the ANP treatment, mild histological changes were observed in few rats in all groups. Therefore, it is concluded that ANP treatment did not cause any mutagenicity or acute toxicity in the winter mushroom.


Repair capability and the cellular age response for killing and mutation induction after UV.
The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D0 of 0.3 as compared to 3.2 J/m2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. A variation in the ability of this repair process to act in eliminating potentially lethal and mutagenic lesions (either due to a variation in repair enzyme activities through the cell cycle, or in the time available for repair) would account for most of the age response which is seen in the wild-type for killing and mutation induction by ultraviolet light.


Critically ischemic myocardium in clinically stable patients following thrombolytic therapy for acute myocardial infarction: potential implications for early coronary angioplasty in selected patients.
The utility of post-thrombolysis, rest-redistribution thallium (TI)-201 scintigraphy was studied in 32 patients with a first myocardial infarction who were clinically stable following reperfusion. Day 1 scintigraphy obtained 5 +/- 4 hours (range 1 to 16) after thrombolysis revealed an average perfusion defect of 6.5 +/- 2.6 segments (range 1 to 11). There was a total of 208 abnormal segments, 137 of which were nonreversible at 4 hours, 50 of which were fully or partially reversible, and 21 of which had a reverse redistribution pattern. Repeat TI-201 scintigraphy on day 10 revealed significantly smaller perfusion defects of 4.9 +/- 2.4 segments (range 0 to 9) with improvement predominantly of the day 1 reversible segments, and the improvement in segmental perfusion correlated with better regional left ventricular function. Twenty-nine (58%) of the 50 reversible segments normalized by day 10, and 11 (22%) improved, whereas only 16 (12%) of 137 nonreversible segments had normalized by day 10, only 9 had (6%) improved and 112 (82%) were unchanged (p less than 0.001 reversible versus nonreversible). There was no significant change in segments with a pattern of reverse redistribution. The improvement of reversible segments was greater in the 16 patients who underwent coronary angioplasty (PTCA) during the interval between the two scintigrams than in the 16 who did not. All 24 reversible segments in the PTCA group improved or normalized by day 10 compared with 16 (62%) of 26 reversible segments in the No PTCA group (p less than 0.001). Furthermore, 8 of the 10 reversible segments in the No PTCA group that did not improve actually deteriorated and became nonreversible by day 10. The minor improvement of nonreversible segments was not related to PTCA. Consistent with the findings in individual segments, the 19 patients with a reversible component on the day 1 TI-201 scintigram had significantly greater improvement in perfusion defect by day 10 than the 13 patients without a reversible component (37 +/- 33% versus 7 +/- 22% decrease in perfusion defect severity, p less than 0.05), and this improvement was greatest in the 10 patients with a reversible component who underwent PTCA. In contrast, PTCA had no impact on the perfusion defect in the 13 patients without a reversible component. Our data suggest that following thrombolytic therapy for acute myocardial infarction, viable myocardium in the reperfused zone may remain ischemic, as manifested by a reversible pattern of TI-201 redistribution at rest, and thus may be in jeopardy of gradual progression to necrosis.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of Neuroinflammation and Autophagy on the Structure of the Blood-Brain Barrier in ADHD Model.
Spontaneously hypertensive rats (SHR) are the most common animal model used to study attention deficit hyperactivity disorder (ADHD). The purpose of this study was to look at the impact of neuroinflammation and autophagy on blood-brain barrier function in the prefrontal cortex and hippocampus of ADHD rats. The rats were separated into three groups: juvenile SHR (6 weeks), mature SHR (12 weeks), and comparable age WKY groups. An open-field test was used to assess rats' ability to move on their own. Immunofluorescence was used to detect the Iba1-immunopositive microglia, ZO-1 and TNF-α. Meanwhile, the expression of p62, Beclin-1, LC3B, and MMP9, MMP2, TNF-α, ZO-1, and occludin were detected by Western blot. The results have shown that Iba1-immunopositive microglia and TNF-α protein in the brain of SHR rats were significantly increased. Moreover, autophagy of cells and the level of MMP2 and MPP9 in the prefrontal cortex and hippocampus increased in SHR rats. In addition, the expression of ZO-1 and occludin was decreased in SHR rats. To sum up, the increase of neuroinflammation and excessive autophagy were essential factors for the damage of blood-brain barrier structure and function.


Effect of leaf nitrogen content of tomato plants on preference and performance of a leafmining fly.
In a study on intraspecific host plant acceptability, Liriomyza trifolii females that had previously been exposed to plants of high nitrogen content, showed a feeding and oviposition preference for plants of high nitrogen (Minkenberg and Fredrix 1989). Females showed a preference to feed and oviposit on the high middle leaves within plants. It was hypothesized that the preference between plants was related to a better performance of females and offspring on high nitrogen plants compared to low nitrogen plants. Different nitrogen dosages were applied to tomato plants, resulting in plants containing 3.4, 3.9, 4.6 or 4.9% leaf nitrogen. L. trifolii females responded to increased leaf nitrogen with significantly increased feeding and fecundity, longer oviposition periods, and higher feeding and oviposition rates. Their offspring on the same plants showed reduced developmental time, lower mortality and increased pupal size. Consequently, intrinsic rate of increase was positively linearly related to leaf nitrogen. Size of L. trifolii females appeared to be independent of fecundity, longevity and developmental time. Pupal length of males increased with increasing developmental time. These results indicate that L. trifolii is well adapted in its intraspecific host plant selection, because the ability to distinguish between plants with differences in leaf nitrogen content will directly lead to an increase in their fecundity, longevity and overall fitness. The implications of leaf nitrogen as a significant factor in the behavior and population dynamics of L. trifolii are discussed.


Association between HLA and red cell antigens. V. A further study of the nature and behaviour of the HLA antigens on red blood cells and their corresponding haemagglutinins.
The variation in the reactivity of red blood cells (RBC) with HLA haemagglutinins was studied, and the influence of some variable factors evaluated. A comparison of the HLA reactivity of RBC with automated and manual methods, showed the superiority of the Auto-Analyzer technique. The similarity in the nature and behaviour of HLA RBC antigens and the related Chido and Rg antigens is discussed. Inhibition/adsorption experiments were performed, and the results did not support the theory that HLA antigens on RBC originate from serum-HLA-active substance. The strength of the HLA reactivity of RBC from a donor was shown to vary from time to time without evidence of clinical disease.


Childhood Hyperlipidemia and its Association with Early Growth Among Full-Term-Born Children at 5 to 6 Years of Age in China.
This study's aim was to assess the prevalence of hyperlipidemia and its association with birth weight and BMI at 2 years of age and 5 to 6 years of age in full-term-born children. A population-based, large-scale survey of hyperlipidemia was conducted. Information on 12,701 children aged 5 to 6 years was retrospectively collected from electronic health care records. The rate of high total cholesterol (≥5.18 mmol/L) and/or high triglycerides (≥1.70 mmol/L) was 10.2%. The multivariate-adjusted odds ratios of high total cholesterol and/or triglycerides were 1.33 (1.04-1.69), 1.00, and 0.95 (0.81-1.11) based on birth weight groups (small for gestational age [SGA], appropriate for gestational age, and large for gestational age); 1.06 (0.77-1.45), 1.00, and 0.99 (0.88-1.11) based on BMI groups at around 2 years of age (<10th, 10th to <75th, and ≥75th percentiles); and 1.56 (1.08-2.25), 1.00, and 1.71 (1.44-2.03) based on BMI groups at 5 to 6 years of age (<-2 SD, -2 SD to <2 SD and ≥2 SD), respectively. In the SGA group, hyperlipidemia was not associated with BMI at 2 years of age but was significantly associated with having underweight or obesity at 5 to <6 years of age. SGA infants are at an increased risk for childhood hyperlipidemia, and catch-up growth before the age of 2 years would not affect this risk. For SGA infants, having underweight or obesity after 2 years of age can increase the risk of childhood hyperlipidemia.


Chronic subdural haematoma: a possible relationship with tamoxifen.
Five patients operated on between 6 months and 7 years earlier for breast cancer were surgically treated for chronic subdural haematoma. This unusual association may be explained on the basis of known factors such as coagulative impairment subsequent to chemotherapy, a degree of cerebral atrophy or mild trauma. On the other hand, since four of the patients were taking antioestrogen therapy to control the disease, it is speculated that the oestrogenic properties of tamoxifen may have contributed to subdural bleeding.


[Elastofibroma dorsi: a 7-year follow-up of 37 cases and a review of the literature].
Elastofibroma dorsi (ED) is an infrequent benign, slow growing, soft tissue tumour that is usually located in the scapular zone. A series of 37 ED patients diagnosed and treated in our hospital between August 1993 and November 2009 were retrospectively reviewed. The average follow up was 7 years. Ten of them presented bilaterally. The male/female ratio was 4:3, and the mean age was 57 years. An MRI was performed, and the diagnosis confirmed by histopathology. Seven cases were treated conservatively. The clinical results were evaluated using a visual analogue score (VAS) for pain and a comparison of the range of movement during follow up. Some 18% of the patients worked or practiced sports that called for the use of the affected limb. The 40% of the patients required a post-operative transfusion was required by 40% of the patients, due to having a haemoglobin <8 g/d. The VAS improved from 6 to 2 after the surgery. The range of movement improved on an average of 40. The complications included an infection, 1 hyperalgesic scar, 8 haematomas and 3 seromas, which were resolved in the follow up without incidence. All the patients were free of illness after a mean follow-up of 85 months. Good results were achieved with a long follow-up. Based on these results and a literature review of the current state of this pathology, an algorithm for its diagnosis and treatment is suggested.


The relationship between N-acetylcysteine, hyperbaric oxygen, and inflammation in a rat model of acetaminophen-induced nephrotoxicity.
An overdose of acetaminophen (APAP) produces acute tubular necrosis. The aim of this study was to observe the effects of hyperbaric oxygen (HBO) only and combined with N-acetylcysteine (NAC) on inflammatory cytokines in kidney. Thirty-two male Sprague-Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC + HBO. In the APAP, NAC, and NAC + HBO groups, renal injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC + HBO group received NAC (100 mg/kg/day) intraperitoneally and HBO underwent at 2.8 ATA pressure with 100 % oxygen inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on 6 days after APAP or distilled water administration. Creatinine, urea, neopterin, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 levels were measured in sera. There was a significant increase in serum creatinine and urea levels in the control group compared to the sham group (in both, p = 0.001). NAC and NAC + HBO significantly decreased serum neopterin, TNF-α, and IL-6 levels compared to control group. APAP administration caused tubular necrosis in the renal. NAC and NAC + HBO treatments significantly reduced APAP-induced renal damage. The results of this study showed that renal dysfunction in APAP toxicity was attenuated by the use of HBO and NAC treatments. The combination of NAC and HBO treatments might be recommended as an effective treatment modality for APAP-induced nephrotoxicity.


Active site model of cytochrome P-450 LM2.
Based on (i) a detailed analysis of the physicochemical properties of selected benzphetamine derived substrates and (ii) the identification of Tyr-380 as active site residue trans to thiolate theoretical studies (computer aided molecular design) revealed a model of the substrate binding site of cytochrome P-450 LM2. The results indicate that substrates with a butterfly-like bulky conformation exhibit the highest intrinsic activity. Those substrates which preferably exist in an extended conformation are sterically hindered to intensively interact with the binding site which is demonstrated by computer graphics.


Anterograde axoplasmic transport of peroxidase in the rat visual system after intraocular neurotoxin injection.
The effect of intraocular injection of the neurotoxin, kainic acid, on the retinofugal pathway has been examined by anterograde transport of horseradish peroxidase. Although less peroxidase was present in all the primary optic centers after the intraocular injection of kainic acid than in the controls, the area occupied by the retinal terminals remained fairly constant except for the pretectal region where there is a smaller area of peroxidase precipitate. These results suggest that certain ganglion cells are killed by kainic acid but some others survive and their terminals are present in the majority of the terminal fields.


Internal exposure risk based on urinary metabolites of PAHs of occupation and non-occupation populations around a non-ferrous metal smelting plant.
The emission of various metals from non-ferrous metal smelting activities is well known. However, relative investigations on potential occupational exposure of organic pollutants are still limited. Herein, total of 619 human urine samples were collected from workers engaged in smelting activities and residents living near and/or far from the smelting sites, and ten mono-hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) in human urine were determined. The median levels of Σ10OH-PAHs in smelting workers (25.6 ng/mL) were significantly higher (p < 0.01) than that of surrounding residents (9.00 ng/mL) and rural residents as the control (8.17 ng/mL), indicating an increase in occupational PAH exposure in non-ferrous metal smelting activities. The composition profiles of OH-PAH congeners were similar in three groups, in which naphthalene metabolites accounted for 76-82% of the total. The effects of smoking, drinking, gender, BMI, and occupational categories on urinary OH-PAHs were considered. The partial correlation analysis showed an insignificant effect of non-ferrous metal smelting activities on PAH exposure for surrounding residents. In the health risk assessments, almost all smelting workers had cancer risks exceeded the acceptable level of 10-6. This study provides a reference to occupational PAH exposure and reinforce the necessary of health monitoring among smelting workers.


The comparison of health care systems through regional analysis: the case of hospital admissions in Belgium and The Netherlands.
One of the problems in the international comparison of health care systems is the small number of units of analysis. Usually only a small number of systems is compared which makes cross-sectional statistical analysis impossible. The two obvious solutions to this problem--neither of which is generally feasible--are either to enlarge the number of systems being compared or to use time series on a small number of health care systems. Quite another solution is to study regional variations within and between a small number of systems. The number of regions has to be sufficiently large to make statistical analysis possible. This is the solution chosen in this article. The phenomenon which is central to our analysis is the number of hospital admissions per 1000 of the population. To explain variations in the hospital admission rate, it is hypothesized that there are a number of variables that have the same kind of influence on hospital admission rates in all western industrialized countries (such as the supply of hospital beds and the health status of the population). On the other hand there are determinants of regional variation in the number of admissions which either exert an influence dependent on the nature of the system, or are unique to a particular health care system. Concerning the first group of hypotheses (the general model), our analysis based on data for 1974 showed that the only variables to have a clear and equal influence on the regional variation in hospital admission rates in the Netherlands as well as in Belgium are the number of hospital beds per 1000 inhabitants and standardized mortality (an operationalization of the concept of health status). The influence of system-specific variables (the second group of hypotheses) has been analysed, taking the difference between the actual number of admissions and the number of admissions expected on the basis of the number of beds and mortality as the dependent variable. In the Netherlands, none of the variables appears to have a clear influence on the level of this ratio, whereas in Belgium there is a greater number of admissions than expected in regions with a higher birth-rate and a higher number of both general practitioners and specialists in the common disciplines (internal medicine, pediatrics, gynaecology) in relation to the total number of specialists.


Cancer: a missing link in ecosystem functioning?
Cancer is a disease that affects the majority of metazoan species and, before directly causing host death, is likely to influence the competitive abilities of individuals, their susceptibility to pathogens, their vulnerability to predators, and their ability to disperse. Despite the potential importance of these ecological impacts, cancer is rarely incorporated into model ecosystems. We describe here the diversity of ways in which oncogenic phenomena, from precancerous lesions to generalized metastatic cancers, may affect ecological processes that govern biotic interactions. We argue that oncogenic phenomena, despite their complexity, can have significant and sometimes predictable ecological consequences. Our aim is to provide a new perspective on the ecological and evolutionary significance of cancer in wildlife, and to stimulate research on this topic.


Indocyanine green intrinsic hepatic clearance as a prognostic index of survival in patients with cirrhosis.
The prognostic value of quantitative liver function tests in patients with cirrhosis is not clearly established. Indocyanine green intrinsic hepatic clearance (ICG-IHC) is a quantitative liver function parameter independent of liver blood flow, which was shown to correlate strictly with the Child-Turcotte-Pugh (CTP) classification of severity of liver disease. Few data are available on its prognostic value. One hundred and five patients with cirrhosis were studied. ICG-IHC was measured according to the 'sinusoidal perfusion' model. Median ICG-IHC in the whole series was 374 ml/min (interquartile range: 214-496 ml/min). During follow-up (mean 31 months; max. 48 months) 38 patients died. The probability of survival was lower in patients with ICG-IHC lower than 300 ml/min (35% at 48 months) than in patients with ICG-IHC between 300 and 1000 ml/min (70%), or with ICG-IHC over 1000 ml/min (80%) (P = 0.02). Also s-albumin (P less than 0.01), ascites (P = 0.001) and CTP class (P less than 0.001) were significant predictors of survival. On incorporation of age, sex, etiology of cirrhosis, ICG-IHC, s-albumin, s-bilirubin, prothrombin index, ascites and encephalopathy, into a multiple regression analysis according to the Cox's model, the results showed only ascites and s-albumin to be independent significant predictors of survival, while ICG-IHC was not among the covariates independently predictive of survival. When CTP class was added to the investigated covariates, the results showed it as the only independent predictor of survival.(ABSTRACT TRUNCATED AT 250 WORDS)


Improved high-performance liquid chromatographic procedure for the determination of chlormethiazole levels following solid-phase extraction from plasma.
An improved high-performance liquid chromatographic method for the determination of chlormethiazole levels in plasma is described. The drug is extracted from plasma using commercially available reversed-phase extraction columns; recovery values obtained using Sep-Pak C18 and Bond Elut C1, C2, C4, C6, C8, C18 columns are compared. Separation was achieved by reversed-phase chromatography, using a mobile phase consisting of 0.025 M sodium acetate buffer, pH 4.5-acetonitrile (67:33) at a flow-rate of 1.6 ml/min in conjunction with a 15-cm Jones Chromatography Apex ODS column. The analytical column was protected by a Waters Assoc. Guard-Pak module containing a Guard-Pak CN insert. Using ultraviolet detection at 254 nm chlormethiazole levels in the region of 50 ng/ml can be measured with only 500 microliter of plasma.


Defect of CD8+ memory T cells developed in absence of IL-12 priming for secondary expansion.
IL-12 priming plays an important role in stimulation of CD8+ effector T cells and development of CD8+ memory T (Tm) cells. However, the functional alteration of CD8+ Tm cells developed in the absence of IL-12 priming is elusive. In this study, we investigated the capacity of secondary expansion of CD8+ Tm cells developed from transgenic OT I CD8+ T cells. The latter cells were in vitro and in vivo stimulated by ovalbumin (OVA)-pulsed dendritic cells [DCOVA and (IL-12-/-)DCOVA] derived from wild-type C57BL/6 and IL-12 gene knockout mice, respectively. We demonstrated that IL-12 priming is important not only in CD8+ T cell clonal expansion, but also in generation of CD8+ Tm cells with the capacity of secondary expansion upon antigen re-encounter. However, IL-12 signaling is not involved in CD8+ Tm cell survival and recall responses. Therefore, this study provides useful information for vaccine design and development.


Compliance of the total respiratory system in healthy preterm and full-term newborns.
The compliance of the total respiratory system (CRS) was determined by the occlusion technique during expiration in 19 preterm newborns (NB) over 31 weeks of gestational age (mean, 34 +/- 1.5 SD) and in 20 full-term NB. Postnatal age ranged from 1 to 28 days. No sedation was used during the test. In absolute terms, CRS was significantly greater (P less than 0.01) in full-term than in preterm NB (3.17 +/- 0.71 ml/cm H2O vs 2.37 +/- 0.81 ml/cm H2O). When normalized for body weight, length cubed, [corrected] body surface area, and the Quetelet index (body weight/length squared) [corrected], CRS was similar in preterm and full-term NB. These results suggest that, normalized for biometric data, passive elastic properties of the total respiratory system are similar in full-term and preterm NB, at least in the gestation age range studied.


Abnormal regulation of de novo purine synthesis and purine salvage in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase.
The isolation and characterization of a mutant murine T-cell lymphoma (S49) with altered purine metabolism is described. This mutant, AU-100, was isolated from a mutagenized population of S49 cells by virtue of its resistance to 0.1 mM 6-azauridine in semisolid agarose. The AU-100 cells are resistant to adenosine mediated cytotoxicity but are extraordinarily sensitive to killing by guanosine. High performance liquid chromatography of AU-100 cell extracts has demonstrated that intracellular levels of GTP, IMP, and GMP are all elevated about 3-fold over those levels found in wild type cells. The AU-100 cells also contain an elevated intracellular level of pyrophosphoribosylphosphate (PPriboseP), which as in wild type cells is diminished by incubation of AU-100 cells with adenosine. However AU-100 cells synthesize purines de novo at a rate less than 35% of that found in wild type cells. In other growth rate experiments, the AU-100 cell line was shown to be resistant to 6-thioguanine and 6-mercaptopurine. Levels of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) measured in AU-100 cell extracts, however, are 50-66% greater than those levels of HGPRTase found in wild type cell extracts. Nevertheless this mutant S49 cell line cannot efficiently incorporate labeled hypoxanthine into nucleotides since the salvage enzyme HGPRTase is inhibited in vivo. The AU-100 cell line was found to be 80% deficient in adenylosuccinate synthetase, but these cells are not auxotrophic for adenosine or other purines. The significant alterations in the control of purine de novo and salvage metabolism caused by the defect in adenylosuccinate synthetase are mediated by the resulting increased levels of guanosine nucleotides.