miRNA expression profile changes in the peripheral blood of monozygotic discordant twins for epithelial ovarian carcinoma: potential new biomarkers for early diagnosis and prognosis of ovarian carcinoma.
Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual's miRNAs. The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms. After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant. The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data. There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.


OntoBrowser: a collaborative tool for curation of ontologies by subject matter experts.
The lack of controlled terminology and ontology usage leads to incomplete search results and poor interoperability between databases. One of the major underlying challenges of data integration is curating data to adhere to controlled terminologies and/or ontologies. Finding subject matter experts with the time and skills required to perform data curation is often problematic. In addition, existing tools are not designed for continuous data integration and collaborative curation. This results in time-consuming curation workflows that often become unsustainable. The primary objective of OntoBrowser is to provide an easy-to-use online collaborative solution for subject matter experts to map reported terms to preferred ontology (or code list) terms and facilitate ontology evolution. Additional features include web service access to data, visualization of ontologies in hierarchical/graph format and a peer review/approval workflow with alerting. The source code is freely available under the Apache v2.0 license. Source code and installation instructions are available at http://opensource.nibr.com This software is designed to run on a Java EE application server and store data in a relational database. firstname.lastname@example.com.


MealMate: improving the nutritional status of elders using a milk-based nutritional supplement.
MealMate was a longitudinal research project conducted by the staff at the Geriatric Health Institute, a joint venture between Sioux Valley Hospital and the University of South Dakota School of Medicine. During Fall 1994, 64 older adults enrolled in this nutrition study at a Sioux Falls congregate dining site and drank a half-pint of whole milk combined with Carnation Instant Breakfast daily for one month. Pre-test and post-test data collected included anthropometric measures, specific blood tests from a venipuncture blood draw and use of standardized instruments to assess nutritional risk, depression, mental status and general demographic information. Results suggest that a longitudinal study with elders can be done effectively (attrition rate of less than 11%). While elders were very healthy at the onset, they nevertheless showed improved nutritional status over time. Laboratory tests showed significant increases in Vitamin D levels in adults over age 79. Using a more malnourished, home-bound sample of elders over age 79 and adding only whole milk to their diets are discussed as possible considerations for future research.


Clarification and capture of high-concentration refold pools for E. coli-based therapeutics using expanded bed adsorption chromatography.
Expanded bed adsorption (EBA) chromatography was investigated for clarification and capture of high-concentration refold pools of Escherichia coli-based therapeutics. Refolding of denatured inclusion bodies (IBs) at high protein concentration significantly improved product throughput; however, direct filtration of the refold materials became very challenging because of high content of protein precipitates formed during refolding. In addition, irreversible protein precipitation caused by high local concentration was encountered in packed bed capture during cation exchange chromatography elution, which limited column loading capacity and capture step productivity. In this study, the two issues are addressed in one unit operation by using EBA. Specifically, EBA can handle feed streams with significant amount of particles and precipitates, which eliminated the need for refold pool clarification through filtration. The relatively broad EBA elution profile is particularly suitable for proteins of low solubility and can effectively avoid product loss previously associated with on-column precipitation during capture. As the EBA resin (RHOBUST(®) FastLine SP IEX) used here has unique properties, it can be operated at high linear velocity (800-1,600 cm/h), while achieving a selectivity and impurity clearance largely comparable to the packed bed resin of the same ligand chemistry (SP Sepharose FF). Furthermore, the filtration of the EBA elution pool is easily manageable within facility capability. Overall, this study demonstrates that the EBA process helps debottleneck the purification of high-turbidity refold pools by removing precipitates and concurrently capturing the product, which can be applied to other E. coli-based therapeutics that also requires refolding of IBs.


Toward a physical environmental continuum for occupational intervention in a rehabilitation hospital.
ABSTRACT A study was conducted to explore occupational therapists' perceptions of rehabilitation environments and the influence of these perceptions on practice and occupational interventions. Traditionally, inpatient occupational therapists have a choice of intervention environments, ranging from a gym-like to a more home-like setting. Choosing to provide interventions in these different environments can have an impact on occupational performance. In this qualitative exploration, 21 occupational therapists participated in focus groups designed to explore their perceptions of practice environments. Analysis of the transcribed data revealed that therapists felt rehabilitation environments should offer choices and be flexible, that environments influenced intervention strategies, and that the practice environment had an impact on professional identity. On the basis of this data, a conceptual matrix of the intersection of environmental setting and occupation-based interventions is presented to highlight the importance of these two aspects of therapy. Future research in this understudied area is needed to transform this matrix into a clinically useful model.


[Endocrine-metabolic adjustments during Ramadan fasting in young athletes].
The Islamic precept of R implies important physiological modifications due to the hydric and dietetic restrictions along a whole month plus a day, all of which have a crucial repercussion over the physical and intellectual performance of Muslims, particularly in occidental societies, in which there is no hour readjustments for daily activities. Among the imposed modifications by Ramadan in daily habits, intermittent fasting along day and night causes adaptation mechanisms to optimize the energy consumption. The objective of this study was to analyze the metabolic-endocrine changes that happen during daily working hours, along the month of fasting in young subjects who have to continue their usual activities and sport training. Ten young muslim subjects, male, healthy, set to sport training, ages in between 18 and 25 who completed Ramadan. Plasma biochemical and hormonal parameters were analyzed in plasma, a week before Ramadan, in the first and fourth of the fasting month and a week after conclusion. During Ramadan, have been observed a drop of biochemical parameters along daytime, especially those related to glycemia, being these changes stronger in the first week. The concentration of cortisol found to be significantly high during the whole month as a consequence of adaptation to the change of circadian secretion rhythms. Ramadan obliges subject's organisms to readjust their endocrine and metabolic system in order to preserve the energetic efficiency during daytime. This auto control becomes more efficient as long as the month advances due to physiological adaptations.


Soft tissue reactions to plaque formation at implant abutments with different surface topography. An experimental study in dogs.
The mucosal attachment that forms to titanium implants, uncontaminated by bacterial plaque comprises, independent of the surface characteristics of the abutment, one barrier epithelium and one zone of connective tissue attachment. It was suggested that abutments with a rough surface may accumulate more plaque than abutments with a smooth surface and that such an enhanced rate of plaque build-up may favor the development of inflammatory lesions in the periimplant mucosa. The aim of the present experiment was to study some reactions of the periimplant mucosa to plaque accumulation on implant abutments designed with either a rough or a smooth external surface. In five beagle dogs, four fixtures were placed and submerged in the premolar region. In a second stage procedure performed after 3 months, abutments with two different types of surface topography, one rough, acid-etched (OA) and one smooth, turned abutment (TA), were installed in a random order. After 6 months of undisturbed plaque formation, the animals were sacrificed and biopsies obtained. Tissue samples were prepared for light microscopy and exposed to histometric and morphometric measurements. Six months of plaque accumulation resulted in the establishment of an inflammatory lesion (pl-ICT) in the connective tissue of the periimplant mucosa, the location, size and composition of which did not differ between OA and TA sites. In addition, most OA and TA sites harbored a second inflammatory cell infiltrate in the tissue lateral to the abutment/fixture junction (ab-ICT). While pl-ICT was dominated by plasma cells and lymphocytes, ab-ICT contained a comparatively large number of polymorphonuclear leukocytes. The different surface characteristics of abutment made of c.p. titanium failed to influence plaque formation and the establishment of inflammatory cell lesions in the periimplant mucosa.


8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver.
8-Cyclopentadienyltricarbonyl 99mTc 8-oxooctanoic acid (99mTc-CpTTOA; 1a) was synthesized for evaluation of medium chain fatty acid metabolism in the liver. 99mTc-CpTTOA was prepared in high radiochemical yield (50-63%) by a double ligand transfer reaction of methyl 8-ferrocenyl-8-oxooctanoate and Na99mTcO4 in the presence of CrCl3 and Cr(CO)6, followed by hydrolysis. This radiotracer was shown to be stable (>90% at 6 h) when incubated with human serum. Aqueous extraction of the radioactivity from the liver and blood samples of mice suggested that 99mTc-CpTTOA was mainly metabolized via beta-oxidation in the liver, and the radioactivity was retained longer in CCl4-treated mice than in control mice, possibly due to impaired beta-oxidation in the former. Planar images of rats injected with 99mTc-CpTTOA showed accumulation of the radioactivity in the liver, kidneys, and bladder with rapid hepatic clearance as a function of time. Analysis of the metabolites from the liver and urine samples of rats further supported that 99mTc-CpTTOA was metabolized to 4-cyclopentadienyltricarbonyl 99mTc 4-oxobutanoic acid (99mTc-CpTTBA; 1c) via beta-oxidation. The results suggested that this radiotracer might be of valuable use in the evaluation of fatty acid metabolism in the liver.


Metabolic state determines sensitivity to cellular stress in Huntington disease: normalization by activation of PPARγ.
Impairments in mitochondria and transcription are important factors in the pathogenesis of Huntington disease (HD), a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. This study investigated the effect of different metabolic states and peroxisome proliferator-activated receptor γ (PPARγ) activation on sensitivity to cellular stressors such as H(2)O(2) or thapsigargin in HD. Striatal precursor cells expressing wild type (STHdh(Q7)) or mutant huntingtin (STHdh(Q111)) were prepared in different metabolic conditions (glucose vs. pyruvate). Due to the fact that STHdh(Q111) cells exhibit mitochondrial deficits, we expected that in the pyruvate condition, where ATP is generated primarily by the mitochondria, there would be greater differences in cell death between the two cell types compared to the glucose condition. Intriguingly, it was the glucose condition that gave rise to greater differences in cell death. In the glucose condition, thapsigargin treatment resulted in a more rapid loss of mitochondrial membrane potential (ΔΨm), a greater activation of caspases (3, 8, and 9), and a significant increase in superoxide/reactive oxygen species (ROS) in STHdh(Q111) compared to STHdh(Q7), while both cell types showed similar kinetics of ΔΨm-loss and similar levels of superoxide/ROS in the pyruvate condition. This suggests that bioenergetic deficiencies are not the primary contributor to the enhanced sensitivity of STHdh(Q111) cells to stressors compared to the STHdh(Q7) cells. PPARγ activation significantly attenuated thapsigargin-induced cell death, concomitant with an inhibition of caspase activation, a delay in ΔΨm loss, and a reduction of superoxide/ROS generation in STHdh(Q111) cells. Expression of mutant huntingtin in primary neurons induced superoxide/ROS, an effect that was significantly reduced by constitutively active PPARγ. These results provide significant insight into the bioenergetic disturbances in HD with PPARγ being a potential therapeutic target for HD.


the management of vulval intraepithelial neoplasia in Northern Ireland.
In this study, we present the findings of a regional retrospective audit of all cases of vulval intraepithelial neoplasia (VIN) diagnosed in Northern Ireland (NI) over an 11-year period (1989-1999). During the period of the study, there were 97 cases of VIN. Cases of VIN were treated by many different clinicians at 14 hospitals. The commonest symptom at presentation was pruritus vulvae. The most common histopathologic diagnosis was VIN III (73%). In 52% of the cases, there was multifocal VIN, and in 43%, there was involvement of other sites such as the cervix, vagina, or anal region. The most common initial treatment was surgical excision, but a multitude of different treatments were performed initially. During the study period, 18 of 90 patients (20%) for whom follow-up was available developed invasive vulval squamous carcinoma. Most of the vulval cancers were superficially invasive, but three patients died of vulval cancer during the study period. This study illustrates that in NI, VIN is treated at many institutions by a multitude of clinicians. Management seems largely dependent on personal clinician preference and has been haphazard with little central coordination and organized strategy. VIN should be managed by clinicians with expertise in this field and who are treating significant numbers of patients according to evidence-based protocols.


[ELISA for diagnosis of infections by viruses].
The assay used most widely to detect or diagnose virus infection, especially infection of blood borne viruses e.g. HBV, HCV, HIV and HTLV, is the enzyme linked immunosorbent assay (ELISA), whose sensitivity and practicability have rendered it the most common primary screening assay. ELISA can be mass screening used automatic or semiautomatic machines. ELISAs can be indirect assay, competition assays or sandwich assays. In indirect and sandwich assays, the development of color indicates the presence of antigen or antibody, whereas in competition assays the absence of color development signifies a positive reaction. Alkaline phosphatase and horseradish peroxidase the most commonly used enzymes, are associated with their respective substrates, usually p-nitro-phenyl phosphate and hydrogen peroxide. The ELISA for antigen detection is used polyclonal antibody or monoclonal antibodies. The other hand, the ELISA for antibody screening is used whole virus, synthetic peptides or recombinant antigens.


Chlordiazepoxide counteracts activity-induced suppression of eating in rats.
Because benzodiazepines such as chlordiazepoxide increase food intake, the present experiments tested the effect of chlordiazepoxide on food intake in an animal model of anorexia nervosa, called activity anorexia (AA). To induce AA, rats (Rattus norvegicus) were maintained in activity wheels and restricted to a single 60-min feeding period each day. As previously found, this procedure suppressed food intake. After several days of this training, food intake was measured 30 min after the rats were injected with chlordiazepoxide (5 mg/kg) or saline. In 2 experiments, chlordiazepoxide counteracted the suppression of food intake produced by AA. Because benzodiazepines have been found to increase food intake in many mammalian species including primates, the present results suggest that benzodiazepines could be useful in the treatment of anorexia nervosa.


Cross-border comparison of antibiotic prescriptions among children and adolescents between the north of the Netherlands and the north-west of Germany.
Antibiotic resistance is a worldwide problem and inappropriate prescriptions are a cause. Especially among children, prescriptions tend to be high. It is unclear how they differ in bordering regions. This study therefore examined the antibiotic prescription prevalence among children in primary care between northern Netherlands and north-west of Germany. Two datasets were used: The Dutch (IADB) comprises representative data of pharmacists in North Netherland and the German (BARMER GEK) includes nationwide health insurance data. Both were filtered using postal codes to define two comparable bordering regions with patients under 18 years for 2010. The proportion of primary care patients receiving at least one antibiotic was lower in northern Netherlands (29.8 %; 95 % confidence interval [95 % CI]: 29.3-30.3), compared to north-west Germany (38.9 %; 95 % CI: 38.2-39.6). Within the respective countries, there were variations ranging from 27.0 to 44.1 % between different areas. Most profound was the difference in second-generation cephalosporins: for German children 25 % of the total prescriptions, while for Dutch children it was less than 0.1 %. This study is the first to compare outpatient antibiotic prescriptions among children in primary care practices in bordering regions of two countries. Large differences were seen within and between the countries, with overall higher prescription prevalence in Germany. Considering increasing cross-border healthcare, these comparisons are highly valuable and help act upon antibiotic resistance in the first line of care in an international approach.


Human microglial cells: characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV-1 infection.
Neuropathological studies have shown that human immunodeficiency virus type 1-infected cells within the brain express several markers characteristic of macrophages and could either be microglial cells, or monocytes invading the CNS, or both. To better define the target cells of human immunodeficiency virus type 1 within the brain, we have studied human microglial cells, both in vivo and in vitro, and compared them to monocytes for their antigenic markers and their susceptibility to human immunodeficiency virus type 1 infection. Brain-derived macrophages were isolated from primary cortical and spinal cord cultures obtained from 8 to 12-week-old human embryos. The isolated cells presented esterase activity, phagocyted zymosan particles, expressed several (Fc receptors, and CD68/Ki-M7 and CD11b/CR3 receptors) of the macrophagic antigenic markers, and appeared to be resident microglial cells from human embryonic brain. Conversely, brain-derived macrophages did not express antigens CD4, CD14, or CD68/Ki-M6, which are easily detected on freshly isolated monocytes. Using these antigenic differences between isolated microglial cells and monocytes, we have observed that two populations of macrophages could be individualized. In the normal adult brain, microglial cells were numerous in both the gray and the white matter. The infrequent cells sharing antigens with monocytes were found almost exclusively around vessels. In 8 to 12-week-old human embryos, microglial cells were found in both the parenchyma and the germinative layer. Cells sharing antigens with monocytes were only found at the top of and inside the germinative layer. In brain tissue from patients with human immunodeficiency virus type 1 encephalitis, cells sharing antigens with monocytes are abundant not only around the vessels but also in the parenchyma. In double-labeling experiments, human immunodeficiency virus type 1-infected cells showed monocyte antigens. Finally, microglial cells also differ from monocytes in their in vitro susceptibility to human immunodeficiency virus type 1 infection; after stimulation by r-TNF alpha or GmCSF, monocytes but not microglial cells can replicate human immunodeficiency virus type 1. This in vitro difference in human immunodeficiency virus type 1 susceptibility between monocytes and microglial cells together with the presence of monocytic antigens within the brain tissue of human immunodeficiency virus type 1-infected patients suggest that human immunodeficiency virus type 1-infected cells within the brain are either monocytes that have crossed the blood-brain barrier and spread through the tissue or perivascular microglial cells that, after phagocyting infected blood lymphocytes, subsequently contain viral antigen and migrate to brain tissue.


Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial.
The doxorubicin-docetaxel combination is active in breast cancer; the aim of the present study was to evaluate the complete response rate and safety profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in metastatic breast cancer patients. Forty-three patients entered the study. Treatment plan was: doxorubicin (50 mg/m2, i.v. bolus) followed 1 hour later by docetaxel (75 mg/m2 i.v. infusion over 1 hour), q 3 weeks, for up to six courses. The patients achieving a response or a stabilisation of disease after 6 courses were allowed to intensify the treatment with docetaxel (100 mg/m2, q 3 weeks) for up to 2 courses. G-CSF (or GM-CSF) was administered if clinically indicated. Patients' median age was 57years (range 32-75) and 72% of them had visceral disease. A total of 217 doxorubicin-docetaxel courses were delivered, with 70% of patients receiving all the 6 planned cycles. Among the 40 patients assessable for response (WHO criteria), 7 (16%) achieved a complete remission and 22 (51%) a partial remission, for an overall response rate (intent-to-treat) of 67% (95% C.I. =53% to 81%). In 19 patients, the treatment was intensified with two more single-agent docetaxel cycles, without ameliorating the response. Twenty-seven patients with oestrogen receptor-positive received hormonal therapy as 'maintenance' after completing chemotherapy treatment. NCIC G3-G4 neutropenia was recorded in 58% of patients, with G/GM-CSF used in 23 (53%) patients and 91 (38%) cycles. No patients experienced severe cardiac or neurological toxicity. No toxic death occurred. With a median follow-up of 41 months among alive patients, we observed in responder patients an overall median time to progression and survival of 18 and 33 months respectively, with ten long-survivors still alive. This study confirmed the combination doxorubicin-docetaxel as a very active regimen for metastatic breast cancer. Remarkably long survival times were observed not only in complete responders, but also in those patients who responded partially. This might be equally attributed to first-line treatment and sequential maintenance hormonal therapy.


lncRNA HOTAIR Promotes DNA Repair and Radioresistance of Breast Cancer via EZH2.
Mounting evidence shows that long noncoding RNAs play important roles in human diseases and radioresistance could be an important factor for tumor recurrence. We observed that HOX antisense intergenic RNA (HOTAIR) expression increased in invasive ductal carcinoma (IDC) tissue. The irradiation effect of HOTAIR was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, cell cycle and apoptosis analysis, and xenografts in nude mice. Western blot, RNA pulldown assay, and RNA immunoprecipitation were used for mechanistic studies. HOTAIR, upregulated in IDC of breast cancer tissue, could promote breast cancer cell proliferation by regulating cell cycle and apoptosis. Overexpression of HOTAIR promoted DNA damage repair factors KU70, KU80, DNA-PKs, and ATM expression, and these could be impeded by small molecular inhibitors of enhancer of zeste homolog 2 (EZH2). Meanwhile, we found that HOTAIR could facilitate recruitment of EZH2 to the Avian Myelocytomatosis Viral Oncogene Homolog (MYC) promoter. HOTAIR is an important modulator not only to the prognostic of breast cancer, but also a good marker for radiotherapy.


Thymic Adenocarcinoma with Positivity for Thyroid Transcription Factor-1 and a BRAF V600E Mutation.
Thymic adenocarcinomas are rare. We herein report for the first time a case of thymic adenocarcinoma with positivity for thyroid transcription factor-1 (TTF-1) and a BRAF V600E mutation. A 50-year-old woman had persistent suffocation and chest pain. Computed tomography revealed a 42×28-mm tumor in the anterior mediastinum. The patient underwent tumor resection using video-assisted thoracoscopic surgery. Histopathological findings showed thymic papillary adenocarcinoma, Masaoka stage II. Immunohistochemically, the tumor was positive for TTF-1. A sequencing analysis revealed a BRAF V600E mutation. The patient underwent postoperative radiotherapy and was in good health without recurrence at five months after resection.


Auxin inhibition of ripening in bartlett pears.
The effect of indoleacetic acid and 2,4-dichlorophenoxyacetic acid on the ripening of intact mature-green pears (Pyrus communis var. Bartlett) was investigated using a vacuum infiltration technique.The effects of indoleacetic acid and 2,4-dichlorophenoxyacetic acid at concentrations of 0.01, 0.1, and 1.0 mm each were studied on softening, degreening, and on ethylene and CO(2) evolution. Softening and degreening were inhibited increasingly in response to increased concentrations of indoleacetic acid. This inhibitory property was amplified by 2,4-dichlorophenoxyacetic acid at concentrations comparable to those of indoleacetic acid. Application of the auxins also prevented the climacteric rise in respiration, but stimulated ethylene synthesis. Despite the presence of elevated ethylene levels, the inhibitory auxin effect was predominant.It is proposed that endogenous auxins in fruit represent a resistance factor in ripening and must be inactivated before ripening can occur.


Anion encapsulation and geometric changes in hepta- and hexanuclear copper(I) dichalcogeno clusters: a theoretical and experimental investigation.
Whereas stable octanuclear clusters of the type M(I)8(E(∩)E)6 (M = Cu, Ag; E(∩)E = dithio or diseleno ligand) are known for being able to encapsulate a hydride or main-group anion under some circumstances, only the related hydride-containing heptanuclear [M(I)]7(H)(E(∩)E)6 and empty hexanuclear [M(I)]6(E(∩)E)6 species have been characterized so far. In this paper we investigate by the means of theoretical calculations and experiments the viability of empty and anion-centered clusters of the type [Cu(I)]7(X)(E(∩)E)6 and [Cu(I)]6(X)(E(∩)E)6 (X = vacancy, H or a main-group atom). The theoretical prediction for the existence of anion-containing heptanuclear species, the shape of which is modulated by the anion nature and size, have been fully confirmed by the synthesis and characterization of [Cu7(X){S2P(O(i)Pr)2}6] (X = H, Br). This consistency between experiment and theory allows us to predict the stability and shape-modulated structure of a whole series of [Cu(I)]7(X)(E(∩)E)6 (X = vacancy, H, O, S, halogen) and [Cu(I)]6(X)(E(∩)E)6 (X = H, halogen) clusters.


Biomimetic Design for Bio-Matrix Interfaces and Regenerative Organs.
The urgent demand for transplanted organs has motivated the development of regenerative medicine to biomimetically reconstruct the structure and function of natural tissues or organs. The prerequisites for constructing multicellular organs include specific cell sources, suitable scaffolding material, and interconnective biofunctional interfaces. As some of the most complex systems in nature, human organs, tissues, and cellular units have unique "bio-matrix" physicochemical interfaces. Human tissues support a large number of cells with distinct biofunctional interfaces for compartmentalization related to metabolism, material exchange, and physical barriers. These naturally shaped biofunctional interfaces support critical metabolic functions that drive adaptive human behavior. In contrast, mutations and disorders during organogenesis can disrupt these interfaces as a consequence of disease and trauma. To replicate the appropriate structure and physiological function of tissues and organs, the biomaterials used in these approaches should have properties that mimic those of natural biofunctional interfaces. In this review, the focus is on the biomimetic design of functional interfaces and hierarchical structures for four regenerative organs, liver, kidney, lung, heart, and the immune system. Research on these organs provides understanding of cell-matrix interactions for hierarchically bioinspired material engineering, and guidance for the design of bioartificial organs. Finally, we provide perspectives on future challenges in biofunctional interface designs and discuss the obstacles that remain toward the generation of functional bioartificial organs.


Concordance between nucleic acid amplification technique and culture for the diagnosis of gonorrhoea.
The objective of the study was to evaluate the concordance between nucleic acid amplification technique (NAAT) and culture for the diagnosis of Neisseria gonorrhoeae among attendees at a genitourinary medicine clinic in East London. All patients testing positive for N. gonorrhoeae on NAAT and/or culture between 1 April 2007 and 31 August 2008 at the Department of Sexual Health at Homerton University Hospital were included. Male patients had a first void urine sample for NAAT and urethral culture; female patients had a self-taken vulval swab or endocervical sample sent for NAAT and an endocervical culture sample. After interim analysis, discrepant results had both NAAT and culture repeated prior to treatment. Of 159 male patients with a positive NAAT, 22 (13%) had a negative culture. Among 135 female patients with a positive NAAT, 36 (27%) had a negative culture. Three men had a positive culture and negative NAAT. Nineteen of the discrepant samples were retested prior to treatment and 12 (63%) had spontaneously revered to negative. In conclusion, there was concordance in 84% of male and 67% of female samples. In two-thirds of the discrepant cases, the previously positive NAAT had become negative prior to treatment. This study highlights the importance of consideration of the clinical picture when assessing results.


Epidemiology of Malnutrition among Children with Cerebral Palsy in Low- and Middle-Income Countries: Findings from the Global LMIC CP Register.
This study aimed to describe the epidemiology of malnutrition among children with cerebral palsy (CP) in low- and middle-income countries (LMICs). Data from children with confirmed CP aged <18 years registered into the Global LMIC CP Register (GLM CPR) from Bangladesh, Indonesia, Nepal, and Ghana were included. Anthropometric measurements were collected, and nutritional status was determined following the WHO guidelines. Descriptive statistics and adjusted logistic regression were used to describe the nutritional status and identify predictors of malnutrition. Between January 2015 and December 2020, 3619 children with CP were registered into the GLM CPR (median age at assessment: 7.0 years, 39% female). Overall, 72-98% of children from Bangladesh, Indonesia, Nepal, and Ghana had at least one form of undernutrition. The adjusted analysis showed, older age, low maternal education, spastic tri/quadriplegia, and Gross Motor Functional Classification System (GMFCS) levels III-V were significant predictors of underweight and stunting among children with CP in Bangladesh. In Nepal, female children, GMFCS III-V had higher odds of underweight and stunting. In Ghana, low maternal education was significantly associated with underweight, whereas older age and the presence of associated impairments were the significant predictors of stunting among children with CP. Having a GMFCS of III-V increased the odds of being underweight among children in Indonesia; however, no predictors were identified for stunting, as nearly all children with CP registered from Indonesia were stunted. Most children with CP in GLM CPR had undernutrition. Maternal education and moderate-to-severe motor impairment (GMFCS III-V) were significant predictors. Practical nutrition education to mothers/caregivers and management guidelines according to the motor severity using local resources could improve the nutritional outcome of children with CP in LMICs.


Percutaneous embolization of ruptured splanchnic artery pseudoaneurysms.
The usefulness of emergent embolotherapy was evaluated in 17 patients with life-threatening hemorrhage from 18 ruptured splanchnic artery pseudoaneurysms. Complete hemostasis was obtained in 16 out of 17 patients by embolotherapy. Of the 12 initial embolization procedures with permanent embolic materials including stainless steel coils, microcoils, and Ivalon, complete cessation of bleeding was obtained in 11. On the other hand, 6 out of 9 initial embolization procedures with Gelfoam particles failed to halt bleeding, and additional embolization with permanent embolic materials was required. Emergent embolization with permanent embolic materials using superselective catheterization should be considered the initial treatment of choice for ruptured splanchnic artery pseudoaneurysms.


Time for Re-Evaluating the Human Carcinogenicity of Ethylenedithiocarbamate Fungicides? A Systematic Review.
In January 2021, the European Union ended the license of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, because of some properties typical of human carcinogens. This decision contrasts the IARC classification of EBDC fungicides (Group 3, not classifiable as to human carcinogenicity). A systematic review of the scientific literature was conducted to explore the current evidence. Human and experimental studies of cancer and exposure to EBDC fungicides (Mancozeb, Maneb, Zineb, and others) and ethylene thiourea (ETU), their major metabolite, published in English as of December 2021, were retrieved using PubMed, the list of references of the relevant reports, and grey literature. The epidemiological evidence of EBDC carcinogenicity is inadequate, with two studies each suggesting an association with melanoma and brain cancer and inconsistent findings for thyroid cancer. Experimental animal studies point at thyroid cancer in rats and liver cancer in mice, while multiple organs were affected following the long-term oral administration of Mancozeb. The mechanism of thyroid carcinogenesis in rats has also been shown to occur in humans. Genotoxic effects have been reported. The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted.


Opportunistic infections associated with retroviral infections in cats.
Naturally occurring infection of cats with feline leukemia virus and feline immunodeficiency virus is common. A wide variety of clinical manifestations occur in retrovirus-infected cats including gastrointestinal tract disease, respiratory tract disease, central nervous system disease, ophthalmic disease, hepatic disease, urogenital tract disease, dermatologic disease, hematologic disease, and musculoskeletal disease. Clinical signs are often directly attributable to the primary viral infection, but because both feline leukemia virus and feline immunodeficiency virus can induce immunodeficiency, opportunistic secondary infections may cause the clinical manifestations of disease in some cats. Diagnosis, treatment, and zoonotic potential of the common opportunistic agents associated with feline retroviral infections are reviewed.


Carnitine deprivation adversely affects cardiac performance in the lipopolysaccharide- and hypoxia/reoxygenation-stressed piglet heart.
Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine and develop low carnitine plasma and tissue levels. Because of its high metabolic rate and dependence on fatty acids for energy, the newborn heart may be particularly vulnerable to stress in the face of an inadequate carnitine supply. To investigate whether carnitine deprivation affects cardiac performance under stress, 23 neonatal piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN -) or supplemented (CARN +) with L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or saline vehicle was administered to anesthetized piglets 3 h prior to study of isolated perfused hearts. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under aerobic, hypoxic, and reoxygenation conditions in all animals. Plasma and tissue carnitine values were lower in CARN - than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in ventricular compliance between CARN - and CARN + groups. LVSP and LVDP were lower in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but left ventricular end diastolic pressure increased in hearts from both LPS- and saline- treated piglets. Reoxygenation led to poorer recovery in CARN - than CARN + hearts from LPS-treated animals, but not from saline controls. During hypoxia/reoxygenation, lactate efflux initially rose and then fell, while carnitine efflux increased continually. Acetyl- and medium-chain acylcarnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impairs cardiac recovery from combined endotoxic and hypoxic stress. Possible mechanisms include reduced acyl buffering and/or impaired transport of fatty acyl groups into mitochondria.


Toughening and functionalization of bioactive ceramic and glass bone scaffolds by biopolymer coatings and infiltration: a review of the last 5 years.
Inorganic scaffolds with high interconnected porosity based on bioactive glasses and ceramics are prime candidates for applications in bone tissue engineering. These materials however exhibit relatively low fracture strength and high brittleness. A simple and effective approach to improve the toughness is to combine the basic scaffold structure with polymer coatings or through the formation of interpenetrating polymer-bioactive ceramic microstructures. The polymeric phase can additionally serve as a carrier for growth factors and therapeutic drugs, thus adding biological functionalities. The present paper reviews the state-of-the art in the field of polymer coated and infiltrated bioactive inorganic scaffolds. Based on the notable combination of bioactivity, improved mechanical properties and drug or growth factor delivery capability, this scaffold type is a candidate for bone and osteochondral regeneration strategies. Remaining challenges for the improvement of the materials are discussed and opportunities to broaden the application potential of this scaffold type are also highlighted.


Validated models for predicting skin penetration from different vehicles.
The permeability of a penetrant though skin is controlled by the properties of the penetrants and the mixture components, which in turn relates to the molecular structures. Despite the well-investigated models for compound permeation through skin, the effect of vehicles and mixture components has not received much attention. The aim of this Quantitative Structure Activity Relationship (QSAR) study was to develop a statistically validated model for the prediction of skin permeability coefficients of compounds dissolved in different vehicles. Furthermore, the model can help with the elucidation of the mechanisms involved in the permeation process. With this goal in mind, the skin permeability of four different penetrants each blended in 24 different solvent mixtures were determined from diffusion cell studies using porcine skin. The resulting 96 kp values were combined with a previous dataset of 288 kp data for QSAR analysis. Stepwise regression analysis was used for the selection of the most significant molecular descriptors and development of several regression models. The selected QSAR employed two penetrant descriptors of Wiener topological index and total lipole moment, boiling point of the solvent and the difference between the melting point of the penetrant and the melting point of the solvent. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.454 for the logkp value of the test set.


[Effect of Kozak sequence on mice DNA vaccine immunization of Staphylococcus aureus adhesion fibronectin-binding protein FnBPA-A].
Fibronectin-binding protein (FnBPA) is a protein that expresses on cell surface of Staphylococcus aureus during early stage of infection. FnBPA was capable of promoting Staphylococcus aureus to invade cells and was viewed as a potential immune target. Based on the FnBPA-A gene two recombinant expression vectors with or without Kozak sequence were constructed. After identified and confirmed by restriction enzyme digestion and sequencing they were used to immunize C57BL/6 mice. Then induced antibody titer, T lymphocyte proliferative response and experiment mice challenge test were measured. Our result indicates that humoral immune responses and challenge experiment induced by recombinant DNA with Kozak sequence were better than those without Kozak sequence (P < 0.05). For T lymphocyte proliferative response the induced effect of recombinant DNA with Kozak sequence was higher than that without Kozak sequence, but there was no significant difference (P > 0.05). We conclude that Kozak sequence could play an important role in immune response induced by FnBPA-A recombinant DNA.


Multi-Omics Revealed the Protective Effects of Rhamnolipids in Lipopolysaccharide Challenged Broilers.
Rhamnolipid (RL) is a glycolipid biosurfactant and exhibits the following outstanding characteristics: strong antibacterial properties, low toxicity, and high biodegradability. The present research was conducted to explore the protective effects and mechanisms of rhamnolipids as an alternative to antibiotics in LPS (lipopolysaccharide)-challenged broilers. 16S rRNA gene sequencing and metabolomics were used for analyzing the cecal microbial composition and serum metabolites. Dietary antibiotics and RLS supplementation decreased the weight loss rate, enhanced serum immunoglobulin levels, reduced serum diamine oxidase and D-lactate acid concentration, and improved the symptoms of intestinal bleeding and villus height, when broilers were challenged with LPS. The addition of RLS in the diet enhanced serum interleukin-4 and interleukin-10 contents and reduced serum interleukin-6 and tumor necrosis factor-α levels in LPS-challenged broilers compared with the antibiotics group. Spearman's correlation analysis revealed that RLS may alleviate LPS-induced inflammatory responses through altering the 6-methoxymellein level in broilers. The genus Bacteroides may contribute to the decreased weight loss rate via regulating the serum lysoPC [20:5(5Z,8Z,11Z,14Z,17Z)] secretion. RLS alleviates LPS-induced intestinal injury, enhances the growth and immunity, ameliorates intestinal microflora, and improves serum metabolites in LPS-challenged broilers. RLS exhibited better protective effect than antibiotic supplementation in the diet of LPS-challenged broilers. These findings provide potential regulation strategies and novel insights for RLS enhancing its protective effect in LPS-challenged broilers.


Characterisation of disproportionating enzyme from wheat endosperm.
Disproportionating enzyme or D-enzyme (EC 220.127.116.11) is an alpha-1,4 glucanotransferase which catalyses cleavage and transfer reactions involving alpha-1,4 linked glucans altering (disproportionating) the chain length distribution of pools of oligosaccharides. While D-enzyme has been well characterised in some plants, e.g. potato and Arabidopsis, very little is known about its abundance and function in cereals which constitute the major source of starch worldwide. To address this we have investigated D-enzyme in wheat (Triticum aestivum). Two putative D-enzyme cDNA clones have been isolated from tissue-specific cDNA libraries. TaDPE1-e, from an endosperm cDNA library, encodes a putative polypeptide of 575 amino acid residues including a predicted transit peptide of 41 amino acids. The second cDNA clone, TaDPE1-l, from an Aegilops taushii leaf cDNA library, encodes a putative polypeptide of 579 amino acids including a predicted transit peptide of 45 amino acids. The mature polypeptides TaDPE1-e and TaDPE1-l were calculated to be 59 and 60 kDa, respectively, and had 96% identity. The putative polypeptides had significant identity with deduced D-enzyme sequences from corn and rice, and all the expected conserved residues were present. Protein analysis revealed that D-enzyme is present in the amyloplast of developing endosperm and in the germinating seeds. D-enzyme was partially purified from wheat endosperm and shown to exhibit disproportionating activity in vitro by cleaving maltotriose to produce glucose as well as being able to use maltoheptaose as the donor for the addition of glucans to the outer chains of glycogen and amylopectin.


Accumulation of extracellular matrix in the liver induces high metastatic potential of hepatocellular carcinoma to the lung.
The liver undergoes pathogenic changes such as hepatitis, fibrosis and cirrhosis under continuous stimulation by hepatitis virus or alcohol intake, leading to the development of hepatocellular carcinoma. The metastatic potential of HCC can be positively or negatively regulated by pathogenic alterations of liver. We investigated whether the metastatic abilities of HCC after orthotopic implantation can be influenced in the fibrotic liver by continuous injection of carbon-tetrachloride (CCl4) for seven weeks. The incidence of lung metastasis after orthotopic implantation of murine HCC (CBO140C12) fragments into CCl4-treated livers was higher than into normal livers. The amount of mRNA for MMP-2 increased in the CCl4-treated livers as compared with normal livers, and CBO140C12 cells constitutively expressed mRNA for MT1-MMP in early amplification cycles by RT-PCR. In addition, we found that the culture of CBO140C12 cells on the substrates pre-coated with ECM components increased the expression of MMP-2 mRNA. Thus, enhanced incidence of lung metastasis in the fibrotic liver might be partly due to: i) over-expression of MMP-2 in the fibrotic liver in cooperation with MT1-MMP on the CBO140C12 cell surface, ii) over-expression of MMP-2 in CBO140C12 cells, possibly mediated by the interaction of tumor cells (surface integrins) with accumulated ECM in the fibrotic liver. This is the first report showing that increase of MMP-2 in the fibrotic liver can influence the metastatic potential of HCC cells.


Recognition of the measles virus nucleocapsid as a mechanism of IRF-3 activation.
The mechanisms of cellular recognition for virus infection remain poorly understood despite the wealth of information regarding the signaling events and transcriptional responses that ensue. Host cells respond to viral infection through the activation of multiple signaling cascades, including the activation of NF-kappaB, c-Jun/ATF-2 (AP-1), and the interferon regulatory factors (IRFs). Although viral products such as double-stranded RNA (dsRNA) and the processes of viral binding and fusion have been implicated in the activation of NF-kappaB and AP-1, the mechanism(s) of IRF-1, IRF-3, and IRF-7 activation has yet to be fully elucidated. Using recombinant measles virus (MeV) constructs, we now demonstrate that phosphorylation-dependent IRF-3 activation represents a novel cellular detection system that recognizes the MeV nucleocapsid structure. At low multiplicities of infection, IRF-3 activation is dependent on viral transcription, since UV cross-linking and a deficient MeV containing a truncated polymerase L gene failed to induce IRF-3 phosphorylation. Expression of the MeV nucleocapsid (N) protein, without the requirement for any additional viral proteins or the generation of dsRNA, was sufficient for IRF-3 activation. In addition, the nucleocapsid protein was found to associate with both IRF-3 and the IRF-3 virus-activated kinase, suggesting that it may aid in the colocalization of the kinase and the substrate. Altogether, this study suggests that IRF-3 recognizes nucleocapsid structures during the course of an MeV infection and triggers the induction of interferon production.


Survey of US obstetrician opinions regarding NIPT use in general practice: implementation and barriers.
To evaluate the knowledge and opinions of US obstetric providers who use noninvasive prenatal testing (NIPT) to understand current utilization and guide future best practices. A questionnaire was designed to assess the level of knowledge and attitudes of OBGYNs toward screening options for aneuploidy, with a focus on NIPT. Initial questions evaluated obstetrician demographics, practice type, and NIPT familiarity. Subsequent questions were designed to solicit current practices regarding aneuploidy screening as well as opinions, experiences, and implications of NIPT. Survey respondents identified NIPT as clinically superior to traditional screening methods and indicated that they would like ACOG to formally recommend NIPT for any pregnant woman. Insurance coverage, and therefore cost, was noted as the biggest barrier, and over 81% of surveyed providers would utilize NIPT as a first-line screening test if patients' insurance offered full coverage. The majority of providers who have implemented NIPT into clinical practice indicated improved patient care. While most providers demonstrated accurate understanding of the technology and its application, nearly 15% misunderstood NIPT as being a diagnostic test for fetal aneuploidy. The results of the survey suggest that there is a desire for changes to current practice guidelines and insurance coverage. Additionally, provider education remains paramount.


An accurate and efficient bayesian method for automatic segmentation of brain MRI.
Automatic three-dimensional (3-D) segmentation of the brain from magnetic resonance (MR) scans is a challenging problem that has received an enormous amount of attention lately. Of the techniques reported in the literature, very few are fully automatic. In this paper, we present an efficient and accurate, fully automatic 3-D segmentation procedure for brain MR scans. It has several salient features; namely, the following. 1) Instead of a single multiplicative bias field that affects all tissue intensities, separate parametric smooth models are used for the intensity of each class. 2) A brain atlas is used in conjunction with a robust registration procedure to find a nonrigid transformation that maps the standard brain to the specimen to be segmented. This transformation is then used to: segment the brain from nonbrain tissue; compute prior probabilities for each class at each voxel location and find an appropriate automatic initialization. 3) Finally, a novel algorithm is presented which is a variant of the expectation-maximization procedure, that incorporates a fast and accurate way to find optimal segmentations, given the intensity models along with the spatial coherence assumption. Experimental results with both synthetic and real data are included, as well as comparisons of the performance of our algorithm with that of other published methods.


Mutations in the cyclic AMP binding site of the cyclic AMP receptor protein of Escherichia coli.
Mutants in the cyclic AMP binding site of the cyclic AMP receptor protein (CRP) of Escherichia coli have been constructed by oligonucleotide-directed mutagenesis. They have been phenotypically characterized and their ability to enhance the expression of catabolite-repressible operons has been tested. In addition, the binding of cyclic nucleotides to the mutants has been investigated. It is shown that the six mutants made fall into one of three classes: (i) those that bind cyclic AMP better than the wild type protein (Ser-62----Ala) and result in greater transcription enhancement; (ii) those that bind cyclic AMP similarly to wild type (Ser-83----Ala, Ser-83----Lys, Thr-127----Ala, Ser-129----Ala); and (iii) those that do not bind cyclic AMP at all (Arg-82----Leu). Implications of these findings with respect to present models of the cyclic nucleotide binding pocket of CRP are discussed.


Cutaneous Radiation Injuries: Models, Assessment and Treatments.
Many cases of human exposures to high-dose radiation have been documented, including individuals exposed during the detonation of atomic bombs in Hiroshima and Nagasaki, nuclear power plant disasters (e.g., Chernobyl), as well as industrial and medical accidents. For many of these exposures, injuries to the skin have been present and have played a significant role in the progression of the injuries and survivability from the radiation exposure. There are also instances of radiation-induced skin complications in routine clinical radiotherapy and radiation diagnostic imaging procedures. In response to the threat of a radiological or nuclear mass casualty incident, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries, including those to the skin. To appropriately assess the severity of radiation-induced skin injuries and determine efficacy of different approaches to mitigate/treat them, it is necessary to develop animal models that appropriately simulate what is seen in humans who have been exposed. In addition, it is important to understand the techniques that are used in other clinical indications (e.g., thermal burns, diabetic ulcers, etc.) to accurately assess the extent of skin injury and progression of healing. For these reasons, the NIAID partnered with two other U.S. Government funding and regulatory agencies, the Biomedical Advanced Research and Development Authority (BARDA) and the Food and Drug Administration (FDA), to identify state-of-the-art methods in assessment of skin injuries, explore animal models to better understand radiation-induced cutaneous damage and investigate treatment approaches. A two-day workshop was convened in May 2019 highlighting talks from 28 subject matter experts across five scientific sessions. This report provides an overview of information that was presented and the subsequent guided discussions.


Emerging techniques in the management of acute pain: epidural analgesia.
Epidural analgesia, often using opioids intraoperatively and postoperatively, is widely accepted as a valuable modality for perioperative pain management. In this review I present data from meta-analyses and recently published trials that evaluate the perioperative use of opioids administered epidurally or parenterally (as-needed or by patient-controlled analgesia) and their effect on outcome. Published effects of perioperative epidural techniques on cardiac and pulmonary function are reviewed. Clinical and practical issues associated with epidural anesthesia and analgesia include the existence of analgesic gaps (often related to technical difficulties with the pump or use of an indwelling catheter), the occurrence of hypotension, and compatibility with anticoagulation therapy. A new treatment option, a single epidural injection of morphine for continuous perioperative analgesia (DepoDur; Endo Pharmaceuticals Inc, Chadds Ford, PA), may reduce some of these problems. Data from recent clinical studies are presented.


Quality of life in patients with locked-in syndrome: Evolution over a 6-year period.
Improved knowledge of the quality of life (QoL) of locked-in syndrome (LIS) patients have implications for managing their care, and assists clinicians in choosing the most appropriate interventions. We performed a survey of a population of LIS patients to describe the course of the QoL of LIS patients over a 6-year period and to determine the potential predictive factors of QoL changes over time. This is a study performed over a 6-year period in patients with a LIS diagnosis. Questionnaires were sent in 2007 and 2013. The following data were recorded: i) sociodemographic data; ii) clinical data related to LIS, physical/handicap status, psychological status; iii) self-reported QoL: Anamnestic Comparative Self-Assessment (ACSA); iv) Integration in life: French Reintegration to Normal Living Index (RNLI). Among the 67 patients included in 2007, 39 (58 %) patients returned their questionnaire in 2013. The LIS etiology was stroke in 51 individuals. The QoL of the patients was relatively satisfactory compared to populations in other severe conditions. Twenty-one (70 %) individuals reported a stable/improved QoL between 2007 and 2013. The physical/handicap statuses in 2007 and 2013 were not related to the QoL 6 years later, with the exception of one communication parameter: the individuals who used yes-no code reported significantly lower QoL levels than those who did not in 2013. In opposition to a widespread opinion, LIS persons report a relatively satisfactory QoL level that stays stable over time, suggesting that life with LIS is worth living. Preservation of autonomy and communication may help them to live as normal life as possible.


Overcoming barriers to population-based injury research: development and validation of an ICD10-to-AIS algorithm.
Hospital administrative databases are a useful source of population-level data on injured patients; however, these databases use the International Classification of Diseases (ICD) system, which does not provide a direct means of estimating injury severity. We created and validated a crosswalk to derive Abbreviated Injury Scale (AIS) scores from injury-related diagnostic codes in the tenth revision of the ICD (ICD-10). We assessed the validity of the crosswalk using data from the Ontario Trauma Registry Comprehensive Data Set (OTRCDS). The AIS and Injury Severity Scores (ISS) derived using the algorithm were compared with those assigned by expert abstractors. We evaluated the ability of the algorithm to identify patients with AIS scores of 3 or greater. We used κ and intraclass correlation coefficients (ICC) as measures of concordance. In total, 10 431 patients were identified in the OTRCDS. The algorithm accurately identified patients with at least 1 AIS score of 3 or greater (κ 0.65), as well as patients with a head AIS score of 3 or greater (κ 0.78). Mapped and abstracted ISS were similar; ICC across the entire cohort was 0.83 (95% confidence interval 0.81-0.84), indicating good agreement. When comparing mapped and abstracted ISS, the difference between scores was 10 or less in 87% of patients. Concordance between mapped and abstracted ISS was similar across strata of age, mechanism of injury and mortality. Our ICD-10-to-AIS algorithm produces reliable estimates of injury severity from data available in administrative databases. This algorithm can facilitate the use of administrative data for population-based injury research in jurisdictions using ICD-10.


Forest Attendance in the Times of COVID-19-A Case Study on the Example of the Czech Republic.
The COVID-19 pandemic affected people all over the world, including the Czech Republic (CZ). In the CZ, a number of measures were applied in 2020 to reduce the contact between people and their mobility. This article dealt with the importance of forests during the pandemic. Data from 2019 and 2020 were compared. The qualitative data were obtained from two nationwide surveys, the first focused on forest attendance and forest fruit collection (about 1000 respondents per year), the second on the motivation to visit the forests (about 3700 respondents per year). The quantitative data were obtained on the regional level by analysing data from mobility counters. The impact of government restrictions was assessed. Findings: (1) there was a significant increase in the number of people who frequently visited the forest in 2020; (2) in 2020, the amount of households that collected forest fruits increased and was the highest for the monitored period; (3) the increased forest attendance significantly corresponded to the government restrictions. The analysis confirmed the great importance of forests for the citizens and, at the same time, the increased pressure on the forests' use-forest attendance and forest crops picking-(especially suburban ones) in times of COVID-19 restrictions.


Probing the internal field gradients of porous media.
We devise a modified Carr-Purcell-Meiboom-Gill pulse sequence that allows us to probe the apparent internal field gradient distribution of a fluid-saturated porous medium as a function of the pore size. This distribution is displayed as a two-dimensional map with one axis being the field gradient, another axis being the T2 relaxation time reflecting different pore sizes, and the vertical amplitudes being proportional to the proton population. Such a scheme of two-dimensional representation for fluid-saturated porous media can also be used for the identification of pore fluids using the contrast of their diffusion coefficients.


Effects of chronic factor VIII substitution on immune parameters in HIV seronegative haemophiliacs: a comparison between cryoprecipitate and factor VIII concentrate.
Chronic substitution therapy of HIV-negative haemophiliacs with factor VIII products can result in abnormalities of ex-vivo measured immune parameters. To assess a possible relation between these abnormalities and product purity, we analyzed two groups of HIV-negative HCV-positive haemophiliacs, one treated with cryoprecipitate exclusively, the other with more purified factor VIII concentrates. Compared to age matched non-transfused male controls, increased numbers of white cells, granulocytes, IgG and IgM levels and decreased CD4+/CD8+ ratios were found in both patient groups. In the concentrate receivers, the numbers of mononuclear cells, CD4+, CD8+ and CD3+/HLA-DR+ cells indicating activated T-cells, were higher than in the cryoprecipitate group. In conclusion, both cryoprecipitate and intermediate/high purity concentrate recipients showed immune parameter abnormalities. These abnormalities tended to be somewhat more pronounced in patients treated with concentrates. By now there is no indication of the clinical relevance of the abnormalities in previously treated HIV seronegative haemophiliacs.


Enzymatic computing.
The conformational dynamics of enzymes is a computational resource that fuses milieu signals in a nonlinear fashion. Response surface methodology can be used to elicit computational functionality from enzyme dynamics. We constructed a tabletop prototype to implement enzymatic signal processing in a device context and employed it in conjunction with malate dehydrogenase to perform the linearly inseparable exclusive-or operation. This shows that proteins can execute signal processing operations that are more complex than those performed by individual threshold elements. We view the experiments reported, though restricted to the two-variable case, as a stepping stone to computational networks that utilize the precise reproducibility of proteins, and the concomitant reproducibility of their nonlinear dynamics, to implement complex pattern transformations.


[Computer-assisted search and optimization of new integrase inhibitor of human immunodeficiency virus].
Finding and optimization of new HIV-1 integrase inhibitors is an important task due to the drawbacks of the existing antiretroviral therapy caused by the significant adverse effects, high cost of the treatment, and emerging resistance. In this study we used computer-assisted methods for finding and optimization of new HIV-1 integrase inhibitors blocking the 3'-processing reaction. Possibility of application of the specialized version of computer program PASS for searching original inhibitors of 3'-processing reaction among the commercially available samples of chemical compounds, belonging to a new chemical class, is shown. We compared the general pharmacological profiles calculated by PASS for the sets of original integrase inhibitors discovered in the study with those for known inhibitors published in literature. It was shown that the predicted average selectivity is close for the compounds from both sets, while the predicted adverse/toxic actions are less for the original compounds. Differences of pharmacological profiles of original compounds and known from literature inhibitors of 3'-processing pointed out to the essential novelty of our substances. Significantly less deviations from the recommended values for QikProp parameters, which characterized the ADME properties, have been observed for the original compounds than for the integrase inhibitors published in literature. Thus, one may come to the conclusion that the original compounds look more prospective comparing to the earlier known inhibitors of 3'-processing.


Induction of lactate dehydrogenase isozymes by oxygen deficit in barley root tissue.
Lactate dehydrogenase (LDH) activity in attached roots of barley and other cereals increased up to 20-fold during several days of severe hypoxia, reaching a maximum of about 2 micromoles per minute per gram fresh weight. In barley, induction of LDH activity was significant at 2.6% O(2) and greatest at 0.06%, the lowest O(2) concentration tested. Upon return to aerobic conditions, induced LDH activity declined with an apparent half-life of 2 days. The isozyme profile of barley LDH comprised 5 bands, consistent with a tetrameric enzyme with subunits encoded by two different Ldh genes. Changes in staining intensity of the isozymes as a function of O(2) level suggested that one Ldh gene was preferentially expressed in severe hypoxia. When tracer [U-(14)C]glucose was supplied to induced roots under hypoxic conditions, lactate acquired label, but much less than either ethanol or alanine. Most of the [(14)C] lactate was secreted into the medium, whereas most other labeled anionic products were retained in the root. Neither hypoxic induction of LDH, nor lactate secretion by induced roots, is predicted from the Davies-Roberts hypothesis, which holds that lactate glycolysis ceases soon after the onset of hypoxia due to acidosis brought about by lactate accumulation in the cytoplasm. These results imply a functional significance for LDH beyond that assigned it in this hypothesis.


Arendse v. Roode, 17 November 1988.
In an action to declare a marriage a nullity on the ground of bigamy, the Court ruled that the plaintiff could obtain damages for injury resulting from her deception as to the fact that the marriage was a nullity and damages for seduction resulting in her loss of virginity and diminished chances of making a suitable marriage.


Abstractive Arabic Text Summarization Based on Deep Learning.
Text summarization (TS) is considered one of the most difficult tasks in natural language processing (NLP). It is one of the most important challenges that stand against the modern computer system's capabilities with all its new improvement. Many papers and research studies address this task in literature but are being carried out in extractive summarization, and few of them are being carried out in abstractive summarization, especially in the Arabic language due to its complexity. In this paper, an abstractive Arabic text summarization system is proposed, based on a sequence-to-sequence model. This model works through two components, encoder and decoder. Our aim is to develop the sequence-to-sequence model using several deep artificial neural networks to investigate which of them achieves the best performance. Different layers of Gated Recurrent Units (GRU), Long Short-Term Memory (LSTM), and Bidirectional Long Short-Term Memory (BiLSTM) have been used to develop the encoder and the decoder. In addition, the global attention mechanism has been used because it provides better results than the local attention mechanism. Furthermore, AraBERT preprocess has been applied in the data preprocessing stage that helps the model to understand the Arabic words and achieves state-of-the-art results. Moreover, a comparison between the skip-gram and the continuous bag of words (CBOW) word2Vec word embedding models has been made. We have built these models using the Keras library and run-on Google Colab Jupiter notebook to run seamlessly. Finally, the proposed system is evaluated through ROUGE-1, ROUGE-2, ROUGE-L, and BLEU evaluation metrics. The experimental results show that three layers of BiLSTM hidden states at the encoder achieve the best performance. In addition, our proposed system outperforms the other latest research studies. Also, the results show that abstractive summarization models that use the skip-gram word2Vec model outperform the models that use the CBOW word2Vec model.


Purification and characterization of cellobiose dehydrogenase from the plant pathogen Sclerotium (Athelia) rolfsii.
Cellobiose dehydrogenase (CDH) is an extracellular hemoflavoenzyme produced by several wood-degrading fungi. In the presence of a suitable electron acceptor, e.g., 2,6-dichloro-indophenol (DCIP), cytochrome c, or metal ions, CDH oxidizes cellobiose to cellobionolactone. The phytopathogenic fungus Sclerotium rolfsii (teleomorph: Athelia rolfsii) strain CBS 191.62 produces remarkably high levels of CDH activity when grown on a cellulose-containing medium. Of the 7,500 U of extracellular enzyme activity formed per liter, less than 10% can be attributed to the proteolytic product cellobiose:quinone oxidoreductase. As with CDH from wood-rotting fungi, the intact, monomeric enzyme from S. rolfsii contains one heme b and one flavin adenine dinucleotide cofactor per molecule. It has a molecular size of 101 kDa, of which 15% is glycosylation, and a pI value of 4.2. The preferred substrates are cellobiose and cellooligosaccharides; additionally, beta-lactose, thiocellobiose, and xylobiose are efficiently oxidized. Cytochrome c (equine) and the azino-di-(3-ethyl-benzthiazolin-6-sulfonic acid) cation radical were the best electron acceptors, while DCIP, 1,4-benzoquinone, phenothiazine dyes such as methylene blue, phenoxazine dyes such as Meldola's blue, and ferricyanide were also excellent acceptors. In addition, electrons can be transferred to oxygen. Limited in vitro proteolysis with papain resulted in the formation of several protein fragments that are active with DCIP but not with cytochrome c. Such a flavin-containing fragment, with a mass of 75 kDa and a pI of 5.1 and lacking the heme domain, was isolated and partially characterized.


The impact of preoperative statin therapy on open and endovascular abdominal aortic aneurysm repair outcomes.
This study evaluated the utilization of preoperative statins and their impact on perioperative outcomes in patients undergoing open or endovascular aortic repair. Patients ≥50 years of age with non-ruptured abdominal aortic aneurysm repair were identified in MedPAR files 2007-2008 utilizing ICD-9-CM codes. Preoperative statins use was identified using National Drug Codes in Part D. Chi-square test, multivariable logistic regression, Kaplan-Meier and Cox regression modeling were performed. In all, 19,323 patients were identified undergoing abdominal aortic aneurysm repair (14,602 endovascular aortic repair and 4721 open aortic repair); 9913 (50.3%) used statins before surgery. Bivariate analysis demonstrated lower rates of hospital, 30-, 90-day and 1-year mortality in patients with statins compared to those without statins after endovascular aortic repair (1.0% vs. 1.45%, p = 0.01; 1.51% vs. 2.3%, p = 0.0004; 3.05% vs. 4.66%, p < 0.0001; 7.91% vs. 11.56%, p < 0.0001, respectively). Multivariable logistic regression adjusting for age, gender, race, comorbidities and procedure demonstrated preoperative statins use was associated with a mortality reduction at 90-days postoperatively (odds ratio = 0.80; 95% CI 0.70-0.91, p = 0.0014) and 1-year postoperatively (odds ratio = 0.76; 95% CI 0.69-0.84, p = 0.0001). Only half of the patients undergoing abdominal aortic aneurysm repair were prescribed preoperative statins. After adjustment, statins were significantly associated with improved survival during 1 year after surgery and a decreased incidence of lower extremity embolic complications after endovascular aortic repair. These data support a beneficial role of statin use prior to surgery for patients undergoing abdominal aortic aneurysm repair. Further prospective studies are needed to assess the benefit of statins in the perioperative period after 365 days.


Beta propellers: structural rigidity and functional diversity.
Recently solved structures and proposed models have helped to reveal the structural characteristics of the beta-propeller fold, as well as the features that contribute to its high rigidity and stability. Possible strategies for identifying beta-propeller proteins in newly characterised sequences are helping to overcome the problems of predicting the beta-propeller fold from amino acid sequences.


PSEUDYANA for NMR structure calculation of paramagnetic metalloproteins using torsion angle molecular dynamics.
The program DYANA, for calculation of solution structures of biomolecules with an algorithm based on simulated annealing by torsion angle dynamics, has been supplemented with a new routine, PSEUDYANA, that enables efficient use of pseudocontact shifts as additional constraints in structure calculations of paramagnetic metalloproteins. PSEUDYANA can determine the location of the metal ion inside the protein frame and allows to define a single tensor of magnetic susceptibility from a family of conformers. As an illustration, a PSEUDYANA structure calculation is provided for a metal-undecapeptide complex, where simulated pseudocontact shifts but no NOE restraints are used as conformational constraints.


Hierarchical imputation of systematically and sporadically missing data: An approximate Bayesian approach using chained equations.
In health and medical sciences, multiple imputation (MI) is now becoming popular to obtain valid inferences in the presence of missing data. However, MI of clustered data such as multicenter studies and individual participant data meta-analysis requires advanced imputation routines that preserve the hierarchical structure of data. In clustered data, a specific challenge is the presence of systematically missing data, when a variable is completely missing in some clusters, and sporadically missing data, when it is partly missing in some clusters. Unfortunately, little is known about how to perform MI when both types of missing data occur simultaneously. We develop a new class of hierarchical imputation approach based on chained equations methodology that simultaneously imputes systematically and sporadically missing data while allowing for arbitrary patterns of missingness among them. Here, we use a random effect imputation model and adopt a simplification over fully Bayesian techniques such as Gibbs sampler to directly obtain draws of parameters within each step of the chained equations. We justify through theoretical arguments and extensive simulation studies that the proposed imputation methodology has good statistical properties in terms of bias and coverage rates of parameter estimates. An illustration is given in a case study with eight individual participant datasets.


Incidence of contrast-induced nephropathy in intensive care patients undergoing computerised tomography and prevalence of risk factors.
Computerised tomography (CT) with contrast is frequently used in intensive care. Contrast-induced nephropathy (CIN) is an important complication largely studied in stable cardiology patients and can lead to acute renal failure. The aim of this study was to determine the incidence of CIN in an intensive care unit (ICU) setting and describe the prevalence of associated risk factors. We performed a retrospective analysis by review of electronic laboratory database and manual chart review of all patients in two tertiary intensive care units in Newcastle, New South Wales who underwent CT with intravenous contrast during their ICU stay in 2006. CIN was defined as an absolute increment in serum creatinine of 44.2 micromol/l or a relative increment of 25% from baseline at 48 to 72 hours following intravenous contrast. Patients' demographic, biochemical and contrast media data, physiological parameters, fluid and drug administrations and previously described as well as ICU specific risk factors were analysed. We compared CIN positive and CIN negative patients to identify risk factors associated with CIN. In total, 2043 patients were admitted to ICU during 2006 and 509 CT studies were performed. One hundred and forty-one of these included administration of intravenous contrast and 139 charts were reviewed. Sixteen out of 139 patients developed CIN (11.5%). More than 70% of patients had two or more risk factors. Age was the only risk factor found to be significantly associated with the development of CIN in a multivariate analysis (P value 0.04, OR 1.041, 95% confidence interval 1.002 to 1.081). Mortality was higher in CIN positive patients (31 vs 13%, P value 0.068). ICU and hospital length of stay was not significantly different in CIN positive and negative patients and persisting renal impairment was not found in CIN positive survivors. Based on this study, we cannot predict who will develop CIN in ICU using the described risk factors. Further prospective studies are needed to evaluate the incidence and outcomes of CIN in an ICU setting.


Classification of difference between inhibition constants of an inhibitor to facilitate identifying the inhibition type.
To identify the common inhibition types, the putative decision system is unsatisfactory. In a new decision system, Michaelis-Menten constants and maximal reaction rates were plotted versus inhibitor concentrations for deriving K(ik) and K(iv) as the inhibition constants, respectively; their difference was quantified as the ratio of the larger one to the smaller one. Such ratios below 2.0 suggested uncompetitive inhibitors, over 5.0 suggested noncompetitive or competitive inhibitors, and from 2.0 to 5.0 suggested mixed inhibitors. By the new decision system, (i) the simulation recovery of uncompetitive inhibitors under CVs of 2% or 5% was improved by four times, but that of competitive or noncompetitive inhibitors was improved slightly; (ii) the recovery of L-phenylalanine as an uncompetitive inhibitor of intestinal alkaline phosphatase reached 38%, while the putative decision system lost all; the recovery of xanthine as a competitive inhibitor of uricase was improved slightly. Therefore, the new decision system was better.


Gap Plasmon Resonance in a Suspended Plasmonic Nanowire Coupled to a Metallic Substrate.
We present an experimental demonstration of nanoscale gap plasmon resonators that consist of an individual suspended plasmonic nanowire (NW) over a metallic substrate. Our study demonstrates that the NW supports strong gap plasmon resonances of various gap sizes including single-nanometer-scale gaps. The obtained resonance features agree well with intuitive resonance models for near- and far-field regimes. We also illustrate that our suspended NW geometry is capable of constructing plasmonic coupled systems dominated by quasi-electrostatics.


The reliability and validity of the psychopathy checklist: youth version (PCL:YV) in nonincarcerated adolescent males.
Current knowledge about the validity of the psychopathy syndrome in youth is limited largely to studies relying on parent-teacher rating scales or slight modifications of adult measures. Recently, the Psychopathy Checklist: Youth Version (PCL:YV) was designed for use with adolescents. However, most studies that have used this measure examined incarcerated males and addressed only validity criteria related to antisocial behavior. We investigated the generality and construct validity of the psychopathy syndrome in an adolescent sample by assessing 115 adolescent males on probation with the PCL:YV. Reliability of measurement was high. PCL:YV ratings predicted not only antisocial behaviour but also other indices of childhood psychopathology, interpersonal behaviors associated with adult psychopathy, and a lack of attachment to parents. These findings suggest that the PCL:YV identifies a syndrome in adolescence consistent with theory and research on adult males.


Cellular therapy: A promising tool in the future of colorectal surgery.
Cellular therapy may be the solution of challenging problems in colorectal surgery such as impaired healing leading to anastomotic leakage and metastatic colorectal cancer (CRC). This review aimed to illustrate the role of cellular therapy in promotion of wound healing and management of metastatic CRC. An organized literature search for the role of cellular therapy in promotion of wound healing and management of metastatic CRC was conducted. Electronic databases including PubMed/Medline, Scopus, and Embase were queried for the search process. Two types of cellular therapy have been recognized, the mesenchymal stem cells (MSCs) and bone marrow-mononuclear cells (BM-MNCs) therapy. These cells have been shown to accelerate and promote healing of various tissue injuries in animal and human studies. In addition, experimental studies have reported that MSCs may help suppress the progression of colon cancer in rat models. This article reviews the possible mechanisms of action and clinical utility of MSCs and BM-MNCs in promotion of healing and suppression of tumor growth in light of the published literature. Cellular therapy has a potentially important role in colorectal surgery, particularly in the promotion of wound healing and management of metastatic CRC. Future directions of cellular therapy in colorectal surgery were explored which may help stimulate futures studies on the role of cellular therapy in colorectal surgery.


Reduced 6,6,8-trimethylpterins. Preparation, properties and enzymic reactivities with dihydropteridine reductase, phenylalanine hydroxylase and tyrosine hydroxylase.
The substrates of dihydropteridine reductase (EC 188.8.131.52), quinonoid 7,8-dihydro(6 H)pterins, are unstable and decompose in various ways. In attempting to prepare a more stable substrate, 6,6,8-trimethyl-5,6,7,8-tetrahydro(3 H)pterin was synthesised and the quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin derived from it is extremely stable with a half-life in 0.1 M Tris/HCl (pH 7.6, 25 degrees C) of 33 h. Quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin is not a substrate for dihydropteridine reductase but it is reduced non-enzymically by NADH at a significant rate and it is a weak inhibitor of the enzyme: I50 200 microM, pH 7.6, 25 degrees C when using quinonoid 6-methyl-7,8-dihydro(6 H)pterin as substrate. 6,6,8-Trimethyl-5,6,7,8-tetrahydropterin is a cofactor for phenylalanine hydroxylase (EC 184.108.40.206) with an apparent Km of 0.33 mM, but no cofactor activity could be detected with tyrosine hydroxylase (EC 188.8.131.52). Its phenylalanine hydroxylase activity, together with the enhanced stability of quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin, suggest that it may have potential for the treatment of variant forms of phenylketonuria.


Tying new knots in synthetic biology.
Recent years have seen the emergence of synthetic biology, which encompasses the engineering of living organisms as well as the implementation of biological behavior in non-living substrates. Many of these engineered systems have harnessed the diverse toolkit of proteins, genes, and cellular processes that nature offers. While these efforts have been fruitful, they have also illustrated the difficulty associated with programming highly complex functions by tapping into cellular processes. Another set of efforts has focused on building circuits, performing computation, and constructing nanoscale machines using nucleic acids. Zhang et al., 2007, Science 318, 1121-1125 and Yin et al., 2008, Nature 451, 318-322 recently demonstrated flexible approaches for the modular construction of such biochemical devices exclusively using DNA. These approaches have exciting implications both for engineering living cells and for mimicking life-like behavior at the nanoscale.


Production, purification, and characterization of a highly glucose-tolerant novel beta-glucosidase from Candida peltata.
Candida peltata (NRRL Y-6888) produced beta-glucosidase when grown in liquid culture on various substrates (glucose, xylose, L-arabinose, cellobiose, sucrose, and maltose). An extracellular beta-glucosidase was purified 1,800-fold to homogeneity from the culture supernatant of the yeast grown on glucose by salting out with ammonium sulfate, ion-exchange chromatography with DEAE Bio-Gel A agarose, Bio-Gel A-0.5m gel filtration, and cellobiose-Sepharose affinity chromatography. The enzyme was a monomeric protein with an apparent molecular weight of 43,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. It was optimally active at pH 5.0 and 50 degrees C and had a specific activity of 108 mumol.min-1.mg of protein-1 against p-nitrophenyl-beta-D-glucoside (pNP beta G). The purified beta-glucosidase readily hydrolyzed pNP beta G, cellobiose, cellotriose, cellotetraose, cellopentaose, and cellohexaose, with Km values of 2.3, 66, 39, 35, 21, and 18 mM, respectively. The enzyme was highly tolerant to glucose inhibition, with a Ki of 1.4 M (252 mg/ml). Substrate inhibition was not observed with 40 mM pNP beta G or 15% cellobiose. The enzyme did not require divalent cations for activity, and its activity was not affected by p-chloromercuribenzoate (0.2 mM), EDTA (10 mM), or dithiothreitol (10 mM). Ethanol at an optimal concentration (0.75%, vol/vol) stimulated the initial enzyme activity by only 11%. Cellobiose (10%, wt/vol) was almost completely hydrolyzed to glucose by the purified beta-glucosidase (1.5 U/ml) in both the absence and presence of glucose (6%). Glucose production was enhanced by 8.3% when microcrystalline cellulose (2%, wt/vol) was treated for 24 h with a commercial cellulase preparation (cellulase, 5 U/ml; beta-glucosidase, 0.45 U/ml) that was supplemented with purified beta-glucosidase (0.4 U/ml).


Age estimation based on pulp/tooth volume ratio measured on cone-beam CT images.
After tooth eruption, the size of the pulp cavity decreases with age owing to deposition of secondary dentine. The aim of this study was to investigate the relation between the chronological age and the ratio of pulp volume (PV) to tooth volume (TV) measurements using CBCT images of single rooted teeth. Maxillary anterior, canine and mandibular canine/premolar CBCT scans of patients older than 15 years of age were collected from the archives between 2013 and 2015 years. Patients with CBCT scans of teeth were seen in detail and patients with known chronological age were included. Teeth with caries, filling or crown restorations, periapical pathologies or pulps that could not be identified were excluded. Consequently, 204 patients with 655 teeth were evaluated. The PV and the TV of each tooth was measured and then the PV/TV ratio was calculated. Simple linear regression analysis was performed in order to predict age estimation by using PV/TV. The PV/TV of all teeth ranged between 0.01 and 0.08. A negative correlation was found between the PV/TV ratio and age (p < 0.05). The regression analysis showed the highest Pearson correlation (0.532) for the maxillary central incisor tooth. Considering measurements of the PV/TV of all assessed teeth, there was no significant difference in the intercept between both gender (p > 0.05). This study revealed that PV/TV ratio was not gender dependent and the strongest correlation was found between the age and PV/TV ratio measured on maxillary central incisors than other teeth.


Contrast Agents Delivery: An Up-to-Date Review of Nanodiagnostics in Neuroimaging.
Neuroimaging is a highly important field of neuroscience, with direct implications for the early diagnosis and progression monitoring of brain-associated diseases. Neuroimaging techniques are categorized into structural, functional and molecular neuroimaging, each possessing advantages and disadvantages in terms of resolution, invasiveness, toxicity of contrast agents and costs. Nanotechnology-based approaches for neuroimaging mostly involve the development of nanocarriers for incorporating contrast agents or the use of nanomaterials as imaging agents. Inorganic and organic nanoparticles, liposomes, micelles, nanobodies and quantum dots are some of the most studied candidates for the delivery of contrast agents for neuroimaging. This paper focuses on describing the conventional modalities used for imaging and the applications of nanotechnology for developing novel strategies for neuroimaging. The aim is to highlight the roles of nanocarriers for enhancing and/or overcome the limitations associated with the most commonly utilized neuroimaging modalities. For future directions, several techniques that could benefit from the increased contrast induced by using imaging probes are presented.


Design considerations for PET scanners.
In 2-D PET scanners employing septa, scattered radiation is reduced by the septa, placing less importance on good energy resolution. Additionally, the reduced sensitivity in 2-D limits the maximum countrates encountered in clinical FDG studies. In contrast, 3-D PET scanners rely on good energy resolution to reduce the scattered radiation and also must deal with countrates, which are typically 5 times higher than in 2-D mode. To achieve good energy resolution, 3 factors must be considered: 1) choice of a scintillator with good intrinsic energy resolution, 2) choice of a crystal dimension which transmits a uniform amount of light to the PMT in order to avoid light loss along the length of the crystal and 3) choice of a crystal-to-PMT coupling which collects a uniform amount of light from all crystals. As PET scanners are being designed using new, faster scintillators for 3-D imaging, the appropriate trade-off between energy resolution and countrate capability must be found to give the best overall system performance. An example of a fully 3-D PET scanner is the Allegro (ADAC Laboratories), which uses GSO as the detector material. Given the right choice of material and design parameters, good quality, high contrast images can be obtained in 3-D in a relatively short time.


Effect of Mahuang Gancao Ganjiang Decoction on Fusion and Fission of Mitochondria and Apoptosis of Lymphocytes in Mice under Cold Stress.
Mahuang Gancao Ganjiang Decoction (MGGD) can effectively alleviate the symptoms of the patients suffering from exogenous cold stress. However, the curative mechanism has not been fully clarified. This study was designed to investigate the effect of MGGD on the apoptosis of lymphocytes induced by cold stress in mice. The model mice were randomly divided into four groups: the normal control group (no handling mice), cold stress group, MGGD + cold stress group, and MGGD group. Lymphocytes of the mice were isolated from the peripheral blood. Electron microscopy analysis revealed cold stress resulted in mitochondrial fragmentation. Accompanied with the change of morphology of mitochondria, ATP production and the activity of respiratory chain complex decreased in these cells. Western blot analysis showed that these cells expressed decreased fusion-related proteins Mitofusin 1 (Mfn1), Mitofusin 2 (Mfn2), and optic atrophy protein-1 (Opa-1) and increased fission-related proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis-1); our results also show that decreased mitochondrial fusion induces cell apoptosis during cold stress. Meanwhile, we found MGGD can inhibit cell apoptosis induced by cold stress through regulating expression level of Mfn1, Mfn2, Drp1, Fis-1, and Opa-1. These findings are very significant for understanding how MGGD regulates cold-stress-induced cell apoptosis.


Comparison of the interactomic networks of different species in terms of accessibility.
Protein-protein interaction networks were investigated in terms of outward accessibility, which quantifies the effectiveness of each protein in accessing other proteins and is related to the internality of nodes. By comparing the accessibility between 144 ortholog proteins in yeast and the fruit fly, we found that the accessibility tends to be higher among proteins in the fly than in yeast. In addition, z-scores of the accessibility calculated for different species revealed that the protein networks of less evolved species tend to be more random than those of more evolved species. The accessibility was also used to identify the border of the yeast protein interaction network, which was found to be mainly composed of viable proteins.


Commentary: Evaluating oversight of human drugs and medical devices.
This article seeks to provide insights into appropriate FDA oversight of nanotechnology. This commentary identifies limitations in the methodology employed and concludes that the analysis would be stronger with a more in-depth institutional dimension based on administrative law and political science research.