Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats.
Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2'-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.


New and emerging chlamydial infections of creatures great and small.
Until recently, our knowledge of the host range and diversity of members of the Chlamydiaceae, obligate intracellular bacterial pathogens of humans and animals, was thought to be nearly complete. Aided by advances in molecular diagnostics, a new picture is emerging, however, that the host barriers may be looser than previously thought for many chlamydial species. While cross-host transmission of chlamydial species is a concern for animal health, new reports highlight an emerging zoonotic risk for several species associated with intensification of farming and the widespread popularity of companion animals. The description of an expanded cohort of new species within this family from avian and reptilian hosts has also highlighted how much we still have to learn about the biology and pathogenicity of the Chlamydiaceae as a whole. Reports emerging about these relatives of the traditional chlamydial pathogens are matched by the continued identification of novel Chlamydia-related bacteria in the phylum Chlamydiae, providing evidence that many may be pathogenic to humans or animals and pose a zoonotic or vector-borne risk. The review examines the new hosts described for well-characterized chlamydial veterinary pathogens, emerging novel chlamydial species and the potential for these to cause disease in their respective hosts.


[Diagnosis, Prognosis, Monitoring of Cardiac Complications of Arterial Hypertension. Hypertensive Heart Disease].
of the study was further investigation of diagnostics and management of cardiac complications of essential hypertension (EH). Retrospective analysis of annual reports of cardiological departments for 10 year period was carried out. Internists (n=330) from 6 regions of Russia participated in the study. Anonymous questioning was used for the study of physicians views on diagnosis, prognostication of outcomes, and monitoring of hypertensive heart disease (HHD). Responses were compared with information from practical clinical recommendations. Clinicians were poorly informed about nosology, echocardiographic criteria of diagnosis of HHD. They did not use prognostication of development of cardiac arrhythmias caused by hypertension. Large portion of participants (39.09%) was not aware of possibilities of drug therapy of HHD. About 1/3 of physicians could not select appropriate indications for echocardiographic examination of patients with EH. One third of participating physicians did not know EH induced echocardiographic changes. These results stress the importance of creation of a complex method of ambulatory monitoring of EH complications. Such method is suggested in this paper.


Modulation of autonomic balance by tumors and viruses.
Autonomic balance, a function generally under host control, is subject to modulation by other signalers. In some cases, modulation of host autonomic function through behavioral and physical stressors exerted by another individual may have negative consequences for the stress recipient by inducing sympathetic bias. Modulation of autonomic function may sometimes benefit one party at the expense of another. Tumors and HIV are examples of illegitimate signalers who may induce host sympathetic bias to promote their own growth and evade host immune surveillance. Paraneoplastic and paraviral syndromes such as hypertrophic osteoarthopathy, QTc prolongation, insomnia, and cachexia could be viewed as epiphenomena related to the tumoral and viral manipulation of host autonomic balance. In a more general framework, other paraneoplastic and paraviral syndromes may represent epiphenomena related to modulation of endocrine, cytokine, and autonomic functions by tumors and viruses to promote their own survival. Spatial distribution of cancers and viruses within the host may reflect affinity for strategic locations that facilitate manipulation of a variety of host functions including autonomic, endocrine, and cytokine regulation. A more general for understanding spatial distribution of diseases based on gradients of autonomic balance in the body are explored. Darwinian perspectives are discussed.


New laser apparatus to measure oscillation amplitude down to picometer at megahertz frequencies.
A laser setup to study shear oscillations at small amplitudes with resonance frequencies up to 3 MHz is presented. The new approach combines gauging of the Gaussian laser beam and a lock-in amplifier. The device is tested with a 3 MHz AT-cut quartz crystal. The oscillation amplitude at the edge of the electrode on the quartz crystal is measured with a resolution of 2 pm.


Informing pre-registration nurse education: a proposal outline on the value, methods and ethical considerations of involving children in doctoral research.
As pre-registration nurse education programmes evolve within the United Kingdom, it is imperative to involve patient/client groups within the research process, as the outcome may invoke a change in the care delivery of the registered nurse (RN). This paper focuses upon children and how children might hypothetically contribute to informing a generic nursing programme in their capacity as a rights holder and expert in their own lives. Even though their contribution and value has been debated around their capacity as research advisor, research participant and co researcher, this paper explores how the child's view of their experience of hospital and of the good nurse could be best captured. Research is a powerful vehicle that can enable their voice to equally inform UK nurse educators and policy makers so that the child's health care needs are effectively met in hospital by RN's who complete a generic programme.


Kinetic Studies for the Reaction of syn-CH3CHOO with CF3CH═CH2.
Hydrofluoroolefins (HFOs, CxF2x+1CH═CH2) have great potential to replace hydrofluorocarbons (HFCs) as refrigerants. Here the kinetics for the reaction of syn-CH3CHOO with CF3CH═CH2 (HFO-1243zf), the simplest of HFOs, have been studied in a flash photolysis flow reactor at a total pressure of 50 Torr, by using the OH laser-induced fluorescence (LIF) method. The bimolecular reaction rate coefficients were measured at temperatures ranging from 283 to 318 K. A weak positive temperature dependence was observed, with an activation energy of 1.41 ± 0.12 kcal mol-1. At 298 K, the measured rate coefficient was (2.42 ± 0.51) × 10-14 cm3 s-1, in the vicinity of the previously reported upper limit value for the reaction of CH2OO with CF3CH═CH2.


Exposure to dissolved TNT causes multilevel biological effects in Baltic mussels (Mytilus spp.).
Baltic mussels (Mytilus spp.) were exposed to the explosive trinitrotoluene (TNT) for 96 h (0.31-10.0 mg/L) and 21 d (0.31-2.5 mg/L). Bioaccumulation of TNT and its degradation products (2- and 4-ADNT) as well as biological effects ranging from the gene and cellular levels to behaviour were investigated. Although no mortality occurred in the concentration range tested, uptake and metabolism of TNT and responses in antioxidant enzymes and histochemical biomarkers were observed already at the lowest concentrations. The characteristic shell closure behaviour of bivalves at trigger concentrations led to complex exposure patterns and non-linear responses to the exposure concentrations. Conclusively, exposure to TNT exerts biomarker reponses in mussels already at 0.31 mg/L while effects are recorded also after a prolonged exposure although no mortality occurs. Finally, more attention should be paid on shell closure of bivalves in exposure studies since it plays a marked role in definining toxicity threshold levels.


Transtracheal aspiration in the horse: a photo essay.
Transtracheal aspiration is used to obtain samples for culture and cytologic examination of respiratory tract secretions and exudates. A 15-cm-long area of the ventral midcervical region is surgically prepared, a small site infiltrated SC with 2-3 ml lidocaine, and a stab incision made in the skin. A trocar with cannula is inserted through the incision and annular ligament into the trachea and the trocar removed. An 8-Fr polypropylene catheter is inserted about 35-40 cm down the trachea and attached to a 30-ml syringe, containing 20 ml sterile saline, with a 3-way stopcock . The saline is rapidly injected and a 3- to 4-ml sample is aspirated after the horse coughs and as the catheter is slowly withdrawn. The catheter and cannula are withdrawn, the area covered with antibacterial ointment and gauze sponges, and elastic tape applied. Complications are rare but include SC emphysema or infection, pneumomediastinum and cartilage ring damage.


Lipid bilayer electrostatic energy, curvature stress, and assembly of gramicidin channels.
Hydrophobic interactions between lipid bilayers and imbedded membrane proteins couple protein conformation to the mechanical properties of the bilayer. This coupling is widely assumed to account for the regulation of membrane protein function by the membrane lipids' propensity to form nonbilayer phases, which will produce a curvature stress in the bilayer. Nevertheless, there is only limited experimental evidence for an effect of bilayer curvature stress on membrane protein structure. We show that alterations in curvature stress, due to alterations in the electrostatic energy of dioleoylphosphatidylserine bilayers, modulate the structurally well-defined gramicidin A monomer <--> dimer reaction. Maneuvers that decrease the electrostatic energy of the unperturbed bilayer promote channel dissociation; we measure the change in interaction energy. The bilayer electrostatic energy thus can affect membrane protein structure by a mechanism that does not involve the electrostatic field across the bilayer, but rather electrostatic interactions among the phospholipid head groups in each monolayer which affect the bilayer curvature stress. These results provide further evidence for the importance of mechanical interactions between a bilayer and its imbedded proteins for protein structure and function.


Association study of NAT2 gene polymorphism and risk of oral cancer in Southern Punjab, Pakistan.
To investigate the single nucleotide polymorphic variations of N-acetyltransferase 2, phase-II metabolising enzyme, and associated risk factors for oral cancer. The case-control study was conducted from November 2017 to April 2018 after approval from the Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan, and comprised oral cancer patients and healthy controls. Single nucleotide polymorphism of the N-acetyltransferase 2 gene associated with oral cancer was analysed. Factors assessed using tetra-primer amplification refractory mutation system polymerase chain reaction included age, smoking, naswar, betel leaves and nuts. Of the 201 subjects, 94(47%) were patients and 107(53%) were controls, while 108(54%) were aged 10-30 years. Single nucleotide polymorphism rs1208 of N-acetyltransferase 2 gene was primarily A803G and Lys268Arg, with allelic frequency of G/A. Age range 51-70 was significantly (p=0.00001) associated with the prevalence of oral cancer in terms of genotypic relationship with A803G. Substantial allelic association was found between the gene and oral cancer (p=0.006895). Smoking increased the cacner risk 7-fold (odds ratio: 7.0). The genetic variant of N-acetyltransferase 2 rs1208 was found to be significantly associated with oral cancer progression and development of associated risk factors.


Fingolimod for the treatment of relapsing multiple sclerosis.
Fingolimod is the first oral agent approved in the USA for the treatment of relapsing forms of multiple sclerosis. Fingolimod is a sphingosine 1-phosphate receptor modulator that binds to sphingosine 1-phosphate receptors on lymphocytes, resulting in a downregulation of the receptor and a reversible sequestration of lymphocytes in lymphoid tissue. Effector memory T cells are not sequestered so that immune surveillance may be minimally affected. Two large-scale Phase III clinical trials have demonstrated the efficacy of fingolimod compared with placebo and intramuscular interferon β-1a in relapsing-remitting multiple sclerosis. Due to its mechanism of action, fingolimod administration may be associated with first-dose bradycardia and macular edema. Therefore, patients should be observed for 6 h at the time of their first dose and undergo ophthalmologic evaluation prior to treatment initiation and at 3-4 months after initiation.


Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: implications for surveillance studies and new adjuvant therapies.
The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow-up 1303 +/- 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow-up 836 +/- 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from -3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of < or =0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of > or =3 have a high risk for recurrence.


Of monkeys and men: Spitz and Harlow on the consequences of maternal deprivation.
In this contribution the reciprocal influence of Harlow and Spitz concerning the consequences of maternal deprivation of monkeys and men, respectively, is described. On the basis of recently disclosed correspondence between Harlow and Spitz, it is argued that not only was Spitz's work on hospitalism an inspiration for Harlow to start his cloth and wire surrogate work with rhesus monkeys but, at the same time, Harlow's work was a new impetus for Spitz's work on the sexual development of (deprived) infants. It is described how the two men first established personal contact in the early 1960s, after Harlow had published his first surrogate papers, how they became close friends subsequently, and inspired each other mutually.


Effects of growth factors and growth factor-extracellular matrix interactions on mouse trophoblast outgrowth in vitro.
A variety of cell types at the blastocyst implantation site produce growth factors that could play important role(s) in the implantation process. Recent evidence indicates that decidual cells and/or embryos produce transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and colony-stimulating factor (CSF-1). Furthermore, receptors for EGF, PDGF, and CSF-1 have been detected on embryonic and trophoblastic cells. The purpose of this study was to investigate the effects of these growth factors and possibly growth factor-extracellular matrix interactions on mouse blastocyst attachment and trophoblast outgrowth in vitro. Various dilutions of the growth factors TGF-alpha, EGF, PDGF, FGF, and CSF-1 were added to cultures of 5-day-old hatched blastocysts in fibronectin-coated plastic wells. Blastocysts were scored for attachment, trophoblast outgrowth, and surface area at 24, 48, and 72 h. Each of these growth factors significantly enhanced trophoblast outgrowth, and a cocktail containing all of the growth factors had a significantly stronger effect. PDGF and FGF, but no other growth factors, also enhanced trophoblast outgrowth following pulsatile incubation with the fibronectin matrix coating of the culture wells, indicating that interactions between these growth factors and extracellular matrix elements could influence implantation. This study suggests that various growth factors may play an important role in the implantation process, that synergistic effects may be obtained by combinations of growth factors, and that interactions between certain growth factors and extracellular matrix elements may be significant.(ABSTRACT TRUNCATED AT 250 WORDS)


NIH Establishes Early Version of Personalized Medicine Platform.
Will "All of Us" provide clues on the origins of various illnesses? Congress hopes that analyzing the medical and biological data of millions of people will boost precision medicine and help predict outcomes.


High prevalence and risk factors of dropout intention among Chinese medical postgraduates.
A high attrition rate in medical students has exacerbated the physician shortage in China. However, few studies have explored the risk factors of dropout intention in medical postgraduates. This study compared the prevalence of dropout intention and mental distress between medical and non-medical postgraduates in China and investigated risk factors for dropout intention. This study also explored the impact of medical postgraduates' perception of the Chinese healthcare environment on their mental status and dropout intention. This cross-sectional study was conducted using online questionnaires from October 2020 to April 2021. Convenience sampling was used to recruit postgraduates in different majors. Outcomes included dropout intention and potential risk factors, including mental distress, quality of life, and fatigue. Medical postgraduates were additionally assessed for healthcare environment satisfaction, burnout, career choice regret, and experiences of workplace violence. A logistic regression model was constructed to evaluate the association between dissatisfaction, mental distress, and turnover intention. A total of 740 medical and 670 non-medical postgraduates participated in the survey. The rates of depression symptoms (33.8% vs. 39.0%, p < 0.001), anxiety symptoms (22.2% vs. 32.4%, p < 0.001), and somatic symptoms (34.7% vs. 42.4%, p = 0.004) were lower in medical postgraduates, while more medical postgraduates (58.4% vs. 48.4%, p < 0.001) reported dropout intention. Dissatisfaction with the healthcare environment (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.17-2.34, p = 0.005), career choice regret (OR: 6.23; 95% CI: 4.42-8.78, p < 0.001), and high perceived stress (OR: 2.74; 95%CI: 1.90-3.94, p < 0.001) remained independently associated with turnover intention. Mental distress is common among postgraduates, calling for timely interventions. Medical postgraduates reported higher turnover intention. Healthcare environment perception also affected the mental health and dropout intentions of medical students. A decent future income, reduced workload, shorter duration medical training, and better doctor-patient relationships are urgently needed.


LEOPARD Syndrome with PTPN11 Gene Mutation Showing Six Cardinal Symptoms of LEOPARD.
LEOPARD multiple congenital anomaly syndrome inherited in an autosomal dominant manner. LEOPARD is an acronym for Lentigines, Eletrocardiographic conduction defects, Ocular hypertelorism, Pulmonary valve stenosis, Abnormalities of the genitalia, Retardation of growth, and Deafness. Clinical diagnosis is primarily based on multiple lentigines, typical facial features, and the presence of hypertrophic cardiomyopathy and/or café-au-lait macules. We report a typical case of LEOPARD syndrome with PTPN11 gene mutation associated with lentigines, electrocardiograph abnormality, ocular hypertelorism, pulmonary valve stenosis, growth retardation, and sensorineural hearing loss.


Expression, refolding and crystallization of Aquifex aeolicus elongation factor P.
Elongation factor P is a universally conserved protein stimulating peptidyltransferase activity during protein synthesis. The factor is sensitive to classical inhibitors of the ribosomal peptidyltransferase activity and is possibly involved in alignment of the substrate tRNAs in the catalytic centre of 70S ribosomes. Elongation factor P from the thermophilic Aquifex aeolicus was overexpressed as a soluble protein in Escherichia coli and crystallized. A fast generally applicable refolding protocol was developed to improve crystal quality and circumvent strong binding of oligonucleotides to the protein. Diffraction data collected to 2.7 A resolution present twinning.


The reproducibility and validity of a self-administered semiquantitative food frequency questionnaire in subjects from South Dakota and Wyoming.
Most validation studies of food frequency questionnaires have been done in populations capable of reporting their diet with unusual accuracy. In this study of ranchers and subjects selected at random, we compared nutrient intakes as assessed with multiple diet records with those assessed with a self-administered food frequency questionnaire (the Harvard-Willett instrument with 116 food items). One hundred thirty-eight subjects from South Dakota and Wyoming, 64 males and 74 females, completed at least one food frequency questionnaire and multiple 1-day diet records (mean = 5 days) during a 6-month to 1-year period. Of invited subjects, 88% participated; 59% of participants had a high school education or less. For 22 dietary nutrients (excluding supplements) and alcohol, the median crude correlation between intakes based on diet records and the food frequency questionnaire completed before the diet records was 0.42; after adjustment for energy, age, and sex, and after correction for attenuation in the correlation coefficients due to error from a limited number of diet records, the median correlation was 0.52. Correlations for men and women were similar. The validity of the food frequency questionnaire in this population was similar to that reported previously and supports the use of self-administered food frequency questionnaires in studies of general populations.


Can vaccination coverage be improved by reducing missed opportunities for vaccination? Findings from assessments in Chad and Malawi using the new WHO methodology.
In 2015, the World Health Organization (WHO) updated the global methodology for assessing and reducing missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. This paper presents the results of two pilot assessments conducted in Chad and Malawi. Using the ten-step global WHO MOV strategy, we purposively selected districts and health facilities, with non-probabilistic sampling of <24 month old children for exit interviews of caregivers and self-administered knowledge, attitudes, and practices (KAP) surveys of health workers. MOV were calculated based on a child's documented vaccination history (i.e., from a home-based record (HBR) or a health facility vaccination register), including selected vaccines in the national schedule. Respondents included caregivers of 353 children in Chad and of 580 children in Malawi. Among those with documented vaccination history, 82% (195/238) were eligible for vaccination in Chad and 47% (225/483) in Malawi. Among eligible children, 51% (99/195) in Chad, and 66% (149/225) in Malawi had one or more MOV on the survey date. During non-vaccination visits, 77% (24/31) of children eligible for vaccination in Chad and 92% (119/129) in Malawi had a MOV compared to 46% (75/164) and 31% (30/96) during vaccination visits, respectively. Among health workers, 92% in Chad and 88% in Malawi were unable to correctly identify valid contraindications for vaccination. The new MOV tool was able to characterize the type and potential causes of MOV. In both countries, the findings of the assessments point to two major barriers to full vaccination of eligible children-a lack of coordination between vaccination and curative health services and incomplete vaccination during vaccination visits. National immunization programs should explore tailored efforts to improve health worker practices and to increase vaccine delivery by making better use of existing health service contacts.


Proportional-Integral Observer-Based State Estimation for Singularly Perturbed Complex Networks With Cyberattacks.
This article investigates the asynchronous proportional-integral observer (PIO) design issue for singularly perturbed complex networks (SPCNs) subject to cyberattacks. The switching topology of SPCNs is regulated by a nonhomogeneous Markov switching process, whose time-varying transition probabilities are polytope structured. Besides, the multiple scalar Winner processes are applied to character the stochastic disturbances of the inner linking strengths. Two mutually independent Bernoulli stochastic variables are exploited to characterize the random occurrences of cyberattacks. In a practical viewpoint, by resorting to the hidden nonhomogeneous Markov model, an asynchronous PIO is formulated. Under such a framework, by applying the Lyapunov theory, sufficient conditions are established such that the augmented dynamic is mean-square exponentially ultimately bounded. Finally, the effectiveness of the theoretical results is verified by two numerical simulations.


Fe@C carbonized resin for peroxymonosulfate activation and bisphenol S degradation.
Aiming at realizing heavy metal recycling and resource utilization, a carbon-based iron catalyst (Fe@C) was synthesized through a resin carbonization method, and adopted for peroxymonosulfate (PMS) activation to remove bisphenol S (BPS), an emerging aquatic contaminant. This study demonstrated that Fe@C exhibited excellent catalytic potential for BPS degradation with a relatively low activation energy (Ea = 29.90 kJ/mol). Kinetic factors affecting the activation performance were thoroughly investigated. The obtained results indicated that Fe@C composite exhibited the superior uniformity with carbon as the framework and granular iron oxide as the coverage. pH increase could cause the inhibitive effect on BPS degradation, while the increasing catalyst loading (0.05-0.5 g/L) was conducive for the catalytic performance of Fe@C, with an optimal PMS concentration at 1.0 mM. A negative influence on BPS degradation was obtained in the presence of SO42-, HCO3- and lower concentration of Cl- (0-20 mM), compared to the promotion at higher concentration of Cl- (>50 mM). Based on the electron spin resonance (ESR) monitoring and radical scavenging results, it is demonstrated that singlet oxygen, a non-radical species, emerged together with ·SO4- and ·OH for BPS degradation. A three-channel catalytic mechanism was verified through typical characterizations. Furthermore, the degradation pathway of BPS was proposed based on the identified intermediates. This novel carbon-based activator for PMS showed notable potential for the waste resin recycling and water decontamination. A novel Fe-based activator carbonized from a saturated resin exhibits excellent performance for Bisphenol S degradation with activated peroxymonosulfate.


Normal mast cell numbers in the tissues of AhR-deficient mice.
The transcription factor aryl hydrocarbon receptor (AhR) acts as an immunomodulatory molecule in several immune cell lineages. Recently, it has been implicated in development and maintenance of immune cells in barrier tissues such as skin and mucosa. To investigate its role on mast cell development and maintenance in skin, peritoneal exudate cells (PECs) and lymph nodes, we studied in depth their phenotype in AhR-deficient mice. Our findings do not provide any evidence for a suspected role of the AhR in mast cell homeostasis.


Associations between childhood maltreatment and adult depression: a mediation analysis.
There is ample evidence showing that childhood maltreatment (CM) is a risk factor for the development of depression in adulthood. However, little is known about the psychological processes mediating this relationship. This study used a large community sample to investigate the mediating role of emotional, cognitive and/or interpersonal dysfunctions on the one hand and posttraumatic stress disorder symptoms on the other hand. One thousand twenty seven participants of a community sample filled out an online survey. Mediation analyses were computed via linear structural equation modelling. Results showed a significant mediation of the association between CM and adult depression via emotional impairments, depressogenic attribution style and symptoms of posttraumatic stress disorder. Our study design was cross-sectional and therefore did not allow testing temporal precedence of mediators and causality. Data was collected retrospectively, a confounding effect of current depressive symptoms on retrospective recall of CM therefore cannot be ruled out. The a priori mediation model showed a good fit with the data. The model suggests promising objectives for further research on CM-related depression and potential treatment targets in the future.


The hundred most-cited publications in orthopaedic knee research.
Despite its limitations, citation analysis remains one of the best currently available tools for quantifying the impact of articles. Bibliometric studies list the "best-sellers" in a single location, and they have been published frequently in many fields during recent years. The purpose of the present study was to report the qualities and characteristics of citation classics in orthopaedic knee research. The database of the Institute for Scientific Information (ISI) was utilized for identification of articles published from 1945 to March 2014. All knee articles that had been published in sixty-five orthopaedic and twenty-nine rheumatology journals and that had been cited at least 200 times were identified. The top 100 were selected for further analysis of authorship, source journal, number of citations, citation rate (both since publication and in 2013), geographic origin, article type, and level of evidence. The publication dates of the 100 most-cited articles ranged from 1948 to 2007, with the greatest number of articles published in the 1980s. Citations per article ranged from 2640 to 287. All articles were published in eleven of the ninety-four journals. The leading countries of origin were the U.S. followed by the U.K. and Sweden. The two main focus areas were sports traumatology and degenerative disease. The number of citations per article was also greatest for articles published in the 1980s. Basic research articles were cited more quickly, but not more often, than clinical articles. Most articles represented Level-IV evidence, followed by Levels II, III, and I. This bibliometric study is likely to include a list of intellectual milestones in orthopaedic knee research. It is apparent that a high level of evidence is not mandatory for an article to gain a large number of citations. Bibliometric reports provide a reflection of the quality of cited research published in a specific field and should therefore provoke thinking within the scientific community.


Noninvasive focused monitoring and irradiation of head tissue phantoms at microwave frequencies.
In this study, new aspects of our research regarding a novel hybrid system able to provide focused microwave radiometric temperature and/or conductivity measurements and hyperthermia treatment via microwave irradiation are presented. On one hand, it is examined whether the system is capable of sensing real-time progressive local variations of temperature and/or conductivity in customized phantom setups; on the other hand, the focusing attributes of the system are explored for different positions and types of phantoms used for hyperthermia in conjunction with dielectric matching layers surrounding the areas of interest. The main module of the system is an ellipsoidal cavity, which provides the appropriate focusing of the electromagnetic energy on the area of interest. The system has been used for the past few years in experiments with different configuration setups including phantom, animal, and human volunteer measurements yielding promising outcome. The present results show that the system is able to detect local concentrated gradual temperature and conductivity variations expressed as an increase of the output radiometric voltage. Moreover, when contactless focused hyperthermia is performed, the results show significant temperature increase at specific phantom areas. In this case, the effect of the dielectric matching layers placed around the phantoms is critical, thus resulting in the enhancement of the energy penetration depth.


Functional correction of CNS phenotypes in a lysosomal storage disease model using adeno-associated virus type 4 vectors.
Lysosomal storage diseases (LSDs) represent a significant portion of inborn metabolic disorders. More than 60% of LSDs have CNS involvement. LSD therapies for systemic diseases have been developed, but efficacy does not extend to the CNS. In this study, we tested whether adeno-associated virus type 4 (AAV4) vectors could mediate global functional and pathological improvements in a murine model of mucopolysaccharidosis type VII (MPS VII) caused by beta-glucuronidase deficiency. Recombinant AAV4 vectors encoding beta-glucuronidase were injected unilaterally into the lateral ventricle of MPS VII mice with established disease. Transduced ependyma expressed high levels of recombinant enzyme, with secreted enzyme penetrating cerebral and cerebellar structures, as well as the brainstem. Immunohistochemical studies revealed close association of recombinant enzyme and brain microvasculature, indicating that beta-glucuronidase reached brain parenchyma via the perivascular spaces lining blood vessels. Aversive associative learning was tested by context fear conditioning. Compared with age-matched heterozygous controls, affected mice showed impaired conditioned fear response and context discrimination. This behavioral deficit was reversed 6 weeks after gene transfer in AAV4 beta-glucuronidase-treated MPS VII mice. Our data show that ependymal cells can serve as a source of enzyme secretion into the surrounding brain parenchyma and CSF. Secreted enzymes subsequently spread via various routes to reach structures throughout the brain and mediated pathological and functional disease correction. Together, our proof-of-principal experiments suggest a unique and efficient manner for treating the global CNS deficits in LSD patients.


[The value of prognostic factors in patients who underwent a resection of pulmonary metastases].
155 patients were operated on pulmonary metastases in Jena during the period from 1.1.1984 to the 31.12.1994. The findings of 151 patients were analysed. 128 patients suffered from a carcinoma, 15 from a sarcoma, 6 from a malignant melanoma and 2 from a Wilms-tumor. The prognostic factors discussed in the international publications at present were investigated in those patients. Significant differences in the long-term survival were found for the following features: a possible radical resection, the tumor entity, the site, the histology and the grading of the primary tumor, the size and the site of the metastases and the resection of recurrent metastases. Tendencies are described for the type of dissemination and the staging of the primary tumor, the site of the pulmonary metastases in the lung lobes, solitary extrapulmonary metastases and more than 6 lung metastases. In addition patients who showed metastases of a renal cell carcinoma are considered separately.


Renal tubular disturbances induced by tributyl-tin oxide in guinea pigs: a secondary Fanconi syndrome.
Painting of tributyl-tin oxide on the skin induced a secondary Fanconi syndrome in guinea pigs. In the urine of these animals, excretion of sodium, chloride, phosphate, glucose and many kinds of amino acids increased and reached a maximum between day 40 and 50. In sera, the concentrations of phosphate and certain amino acids were low due to excessive loss into urine. Histological examination of the kidney revealed damage to the tubular epithelium with no glomerular change. It was also found that cytochrome P-450 in the kidney and 1-25-dihydroxy vitamin D in serum were reduced in the tin-treated animals. It is most likely that tributyl-tin oxide caused a secondary Fanconi syndrome as defined by renal tubular disturbances represented by glucosuria, generalized amino aciduria, phosphaturia, and hypophosphatemia.


Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats.
Neuronal apoptosis is a crucial pathological process in early brain injury after subarachnoid hemorrhage (SAH). The effective therapeutic strategies to ameliorate neuronal apoptosis are still absent. We intended to determine whether intranasal administration of exogenous Netrin-1 (NTN-1) could attenuate neuronal apoptosis after experimental SAH, specifically via activating DCC-dependent APPL-1/AKT signaling cascade. Two hundred twenty-five male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH. Recombinant human NTN-1 (rNTN-1) was administered intranasally. NTN-1 small interfering RNA (siRNA), APPL-1 siRNA, and AKT inhibitor MK2206 were administered through intracerebroventricular (i.c.v.) injection. SAH grade, neurological score, neuronal apoptosis assessed by cleaved caspase-3 (CC-3) expression and Fluoro-Jade C (FJC) staining, double immunofluorescence staining, and Western blot were examined. Our results revealed that endogenous NTN-1 level was increased after SAH. Administration of rNTN-1 improved neurological outcomes at 24 h and 72 h after SAH, while knockdown of endogenous NTN-1 worsened neurological impairments. Furthermore, exogenous rNTN-1 treatment promoted APPL-1 activation, increased phosphorylated-AKT and Bcl-2 expression, as well as decreased apoptotic marker CC-3 expression and the number of FJC-positive neurons, thereby alleviated neuronal apoptosis. Conversely, APPL-1 siRNA and MK2206 abolished the anti-apoptotic effect of exogenous rNTN-1 at 24 h after SAH. Collectively, intranasal administration of exogenous rNTN-1 attenuated neuronal apoptosis and improved neurological function in SAH rats, at least in apart via activating DCC/APPL-1/AKT signaling pathway.


Rational Design and Synthesis of Carboxylate Gemini Surfactants with an Excellent Aggregate Behavior for Nano-La2O3 Morphology-Controllable Preparation.
A series of carboxylate gemini surfactants (CGS, Cn-Φ-Cn, n = 12, 14, 16, 18) with diphenyl ketone as a spacer group were prepared using a simple and feasible synthetic method. These CGS exhibited an excellent surface activity with extremely low critical micelle concentration (CMC) value (approximately 10-5 mol/L), good performance in reducing surface tension (nearly 30 mN/m), and the ability of molecular self-assembly into different aggregate morphologies via adjusting the concentrations, which is attributed to the introduction of diphenyl ketone and carboxylic acid ammonium salt in the molecular structure. Moreover, the surface activity and self-assembly ability of CGS were further optimized by tuning the length of the tail chain. These excellent properties imply that CGS can be a soft template to prepare nanomaterials, especially in morphology-controllable synthesis. By adjusting the concentration of one of CGS (C12-Φ-C12), nano-La2O3 particles with diverse morphologies were obtained, including spherical shape, bead-chain shape, rod shape, velvet-antler shape, cedar shape, and bowknot shape. This work offers a vital insight into the rational design of template agents for the development of morphology-controllable nanomaterials.


Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis.
We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43-21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36-15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10-0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30-6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39-17.57; p = 0.014). Several subtle immune defects are found in CPA.


Moderate alcohol use and cardiovascular disease from Mendelian randomization.
Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use. We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study. ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45). Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.


Static ocular counterroll is implemented through the 3-D neural integrator.
Static head roll about the naso-occipital axis is known to produce an opposite ocular counterroll with a gain of approximately 10%, but the purpose and neural mechanism of this response remain obscure. In theory counterroll could be maintained either by direct tonic vestibular inputs to motoneurons, or by a neurally integrated pulse, as observed in the saccade generator and vestibulo-ocular reflex. When simulated together with ocular drift related to torsional integrator failure, the direct tonic input model predicted that the pattern of drift would shift torsionally as in ordinary counterroll, but the integrated pulse model predicted that the equilibrium position of torsional drift would be unaffected by head roll. This was tested experimentally by measuring ocular counterroll in 2 monkeys after injection of muscimol into the mesencephalic interstitial nucleus of Cajal. Whereas 90 degrees head roll produced a mean ocular counterroll of 8.5 degrees (+/-0.7 degrees SE) in control experiments, the torsional equilibrium position observed during integrator failure failed to counterroll, showing a torsional shift of only 0.3 degrees (+/-0.6 degrees SE). This result contradicted the direct tonic input model, but was consistent with models that implement counterroll by a neurally integrated pulse.


[Revenue for the German federal budget from cigarette smoking by persons younger than 18 years].
The purpose of this study was to estimate the tax value of tobacco products consumed by persons younger than 18 years in 2007. Tax, population, and consumption data were used to compute an estimate of the tax value of tobacco products consumed by minors. Youth smoking generated an estimated 193 Million Euro in federal tax revenue in one year. The revenues from cigarettes smoked by youth should be used to finance youth-specific prevention programmes.


[Hemostasis monitoring in intensive therapy--studies using resonance thrombography].
The resonance-thrombogram (RTG) is the result of a new investigation method verifying the clotting process as a whole. It provides a far reaching breakdown of the main factors of coagulation and thus a means for diagnosing and treating coagulation disorders. A special field of application is indication and control of therapy in cases of disseminated intravascular clotting and hyperfibrinolysis in intensive care. Simple operation, relatively quick results and the possibility of rapid diagnosis using the RTG curve appear to make it suitable as a bed-side method of investigating blood coagulation.


Circulating MicroRNAs in Serum from Cattle Challenged with Bovine Viral Diarrhea Virus.
Bovine viral diarrhea virus (BVDV) is an RNA virus that is often associated with respiratory disease in cattle. MicroRNAs have been proposed as indicators of exposure to respiratory pathogens. The objective of this study was to identify microRNAs in cattle that had been challenged with a non-cytopathic field strain of BVDV. Five colostrum deprived neonate Holstein calves were inoculated with BVDV (challenged) and 4 were mock challenged (control). Serum from all calves was collected at four different times: prior to challenge (day 0) and at 4, 9, and 16 days post-challenge. RNA was extracted from sera, and expression, via read counts, of small non-coding RNAs were obtained using next-generation sequencing. A total of 905,861 sequences identified 427 microRNAs. Sixty-two microRNAs had >1,000 total reads across all samples. Bta-miR-339a, bta-miR-185, bta-miR-486, Bta-miR-92a, bta-miR-30e-5p, bta-let-7c, and bta-miR-2284x were significantly different (P < 0.05) across time regardless of challenge status. Bta-miR-423-5p (P = 0.008) and bta-miR-151-3p (P = 0.005) were significantly different between challenged and control animals across time. In challenged animals, bta-miR-423-5p peaked in number of reads by day 4 and steadily declined from day 4 to day 16. In control animals, bta-miR-423-5p declined from day 0 to day 9 and increased in number by day 16. By day 16, both challenged and control animals had similar levels of bta-miR-423-5p, and these levels were similar to day 0 levels. Bta-miR-151-3p peaked at day 9 in challenged animals, while control animals decreased across time. By day 16, the number of reads of bta-miR-151-3p were similar between challenged and control animals. The level in challenged animals had returned to day 0 levels by day 16, whereas the levels for control animals was significantly lower (P = 0.006) than day 0. Further studies are needed to establish if bta-miR-423-5p or bta-miR-151-3p could be used as a biomarker for exposure to BVDV.


Seroprevalence of Toxoplasma gondii among HIV Patients in Jahrom, Southern Iran.
Toxoplasma gondii is an important opportunistic agent especially in immunocompromised hosts and can cause significant morbidity and mortality. Hence, detection and monitoring of anti-Toxoplasma antibodies are of a great interest in HIV-infected patients. A study on the prevalence of toxoplasmosis and associated risk factors was carried out among HIV-infected patients in Jahrom, southern Iran. The prevalence of anti-Toxoplasma IgG antibodies was 21.1% in HIV-infected patients by ELISA. PCR was performed on all of the samples, and 1 of the blood samples was positively detected. Among the HIV patients, anti-Toxoplasma IgG antibodies were significantly higher in age group of 30-39 years old (P=0.05). The seroprevalence of toxoplasmosis in patients with CD4+<100 cells/μl was 33.3% that was significantly higher than the other groups (P=0.042) with or without IgG antibodies. The CD4+ count mean of seropositive patients was lower than that of seronegative patients. The seroprevalence of toxoplasmosis in patients with highly active antiretroviral therapy was significantly less than patients without therapy (P=0.02). In conclusion, this study showed low seroprevalence of latent toxoplasmosis among HIV-infected patients in the region and confirmed the need for intensifying prevention efforts among this high-risk population and also the risk of toxoplasmosis reactivation which could be important among this population.


In vitro digestion of fresh alfalfa under different conditions of ruminal pH.
Relatively low ruminal pH values have been frequently registered in dairy cows grazing alfalfa, which can be involved in reducing feed digestion. An in vitro experiment was carried out to study the effect of ruminal pH (6.4, 6.1, 5.8 and 5.5) on the digestion of fresh alfalfa. Decreasing the pH, in vitro gas production (ivGP) decreased (P < 0.05). The lowest ivGP was registered at pH 5.5 and it was product of a higher lag time and a lower digestion rate. Dry matter disappearance (DMD) was not affected by pH at 48 h (P > 0.05). Neutral detergent disappearance (NDFD) at 48 h decreased below pH 6.1. The NDFD was reduced by 62% at pH 5.5 with respect to results at pH 6.4 and 6.1 (where the highest DMD and NDFD were observed). As expected, low rumen pH decreased alfalfa digestion. However, limits to ruminal digestion activity differed from those usually proposed for TMR diets. It is apparent that different relationships between rumen pH and NDFD exist when cows graze fresh alfalfa or grasses. Moreover, our results suggest the convenience to complement the data obtained through ivGP, DMD and NDFD. While ivGP and DMD seem to be more useful at early digestion times, NDFD may be a good predictor of final digestion.


Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9.
In this report we provide evidence, for the first time, that bacterial DNA in the context of heat-killed Brucella abortus (HKBA) engages TLR9 in dendritic cells (DC), resulting in a Th1-like cytokine response. This is based on the findings that HKBA induction of IL-12p40 is: 1) abolished in DC from TLR9(-/-) mice; 2) blocked by suppressive oligodeoxynucleotides; 3) simulated by bacterial DNA derived from HKBA; and 4) abrogated by DNase or methylation of the DNA from HKBA. Furthermore, the effect of HKBA can be inhibited by chloroquine, indicating that endosomal acidification is required and supporting the notion that DNA from HKBA is interacting with TLR9 at the level of the endosome, as is the case with CpG oligodeoxynucleotides. In addition to DC, HKBA can elicit IL-12p40 secretion from macrophages, in which case the effect is wholly MyD88 dependent but only partially TLR9 dependent. This probably explains why HKBA effects in vivo are only partially reduced in TLR9(-/-), but absent in MyD88(-/-) mice. Because of their intimate interactions with T cells, the DC response is most likely to be critical for linking innate and adaptive immune responses, whereas the macrophage reaction may play a role in enhancing NK cell and bystander immune responses. In addition to IL-12p40, HKBA induces other Th1-like cytokines, namely, IFN-alpha and IFN-gamma, in a TLR9-dependent manner. These cytokines are important in protection against viruses and bacteria, and their induction enhances HKBA as a potential carrier for vaccines.


Contribution of pharmacologic tests to the diagnosis of left ventricular regurgitations and obstructions: a phono-echocardiographic confrontation.
Pharmacologic interventions--procedures akin to exercise tests--facilitate, and sometimes permit, the diagnosis of left ventricular regurgitations and obstructions. Particularly when, at rest, the resulting murmur a) is soft or atypical (or absent) and, b) reflects a disease combining both mechanisms (obstruction and regurgitation) during systole. In these circumstances, the echocardiogram may be nondiscriminating or incomplete, and the pharmacologic tests difficult to carry out and to interpret with this technique. Hence the necessity to combine both diagnostic procedures, phonocardiography with pharmacologic intervention, on the one hand; echocardiography, on the other. Each method provides specific and complementary information.


[Echography and computerized tomography in the diagnosis of complex abdominal lesions].
Complex abdominal lesions include a variety of pathologies, such as septated, infected, and hemorrhagic cysts, abscesses, tumors, and fluid collections of different etiology. These lesions present diagnostic difficulties with both Ultrasonography (US) and Computed Tomography (CT), since findings may not be present or, when present, are not specific. Keeping these limitations in mind, we evaluated 105 patients (111 abdominal lesions) with both US and CT in order to compare their adequacy in predicting the nature of the lesion. On the basis of US and CT results, complex abdominal lesions were divided in four classes: class I includes 43 cases in which both examinations gave the same contribution to the definition of the nature of the lesion, class II (14 lesions, mainly sepimentated cysts), in which US was superior to CT, class III includes 45 cases in which CT was superior to US, mainly in case of hemorrhagic cysts, abscesses, fluid collections and, less frequently, cystic tumors; class IV includes 9 cases in which US and CT results were complementary, which allowed the nature of the lesion to be defined. In conclusion, US and CT enable the identification and the characterization of complex abdominal lesions; an association of the two investigations enhances their diagnostic value. As a rule, CT is superior when the content of the lesion is either gas or hemorrhage, and in the definition of its peripheral wall. US is always superior in assessing septa, and sometimes even vegetations.


Comparison of weight change between face-to-face and digital delivery of the English National Health service diabetes prevention programme: An exploratory non-inferiority study with imputation of plausible weight outcomes.
Worldwide evidence suggests face-to-face diabetes prevention programmes are effective in preventing and delaying the onset of type 2 diabetes by encouraging behaviour change towards weight loss, healthy eating, and increased exercise. There is an absence of evidence on whether digital delivery is as effective as face-to-face. During 2017-18 patients in England were offered the National Health Service Diabetes Prevention Programme as group-based face-to-face delivery, digital delivery ('digital-only') or a choice between digital and face-to-face ('digital-choice'). The contemporaneous delivery allowed for a robust non-inferiority study, comparing face-to-face with digital only and digital choice cohorts. Changes in weight at 6 months were missing for around half of participants. Here we take a novel approach, estimating the average effect in all 65,741 individuals who enrolled in the programme, by making a range of plausible assumptions about weight change in individuals who did not provide outcome data. The benefit of this approach is that it includes everyone who enrolled in the programme, not restricted to those who completed. We analysed the data using multiple linear regression models. Under all scenarios explored, enrolment in the digital diabetes prevention programme was associated with clinically significant reductions in weight which were at least equivalent to weight loss in the face-to-face programme. Digital services can be just as effective as face-to-face in delivering a population-based approach to the prevention of type 2 diabetes. Imputation of plausible outcomes is a feasible methodological approach, suitable for analysis of routine data in settings where outcomes are missing for non-attenders.


Use of low-frequency repetitive transcranial magnetic stimulation to reduce context-dependent learning in people with Parkinson's disease.
Compared with age-matched non-disabled adults, people with Parkinson's disease (PD) demonstrated greater context-dependent learning, a phenomenon in which an individual shows inferior motor performance when the testing environmental context is different from the original practice context. Additionally, enhanced context-dependency has been shown to be associated with an increased activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine whether context-dependent learning in people with PD could be reduced by decreasing DLPFC activation with low frequency repetitive transcranial magnetic stimulation (rTMS). Quasi-experimental pre-/post-test controlled study. University laboratory. Twenty-seven participants (18 individuals with PD and 9 age-matched non-disabled adults) were recruited into the PD, PD_rTMS (PD participants who received low frequency rTMS), and Control groups. All participants practiced a finger sequence task containing 3 sequences embedded within specific contexts (colored circles and spatial location on a computer screen) on the first day. On day 2, the participants were tested under the SWITCH and SAME conditions. In the SWITCH condition, the sequence-context association changed from that of practice; in the SAME condition, the sequence-context association remained the same as practice. The PD_rTMS group received 1 Hz rTMS applied over the left DLPFC on the second day before the testing conditions. Switch cost, the performance difference between the SWITCH and SAME conditions, was calculated to indicate context-dependency. All participants improved throughout practice on the first day. Analysis of the switch cost revealed a significant group main effect (P=0.050). Post-hoc analysis revealed that the PD_rTMS group had significantly smaller switch cost than the PD group (P=0.031) but not the control group. Low frequency rTMS applied over DLPFC reduced context-dependency in people with PD. The findings provide a preliminary evidence of using low frequency rTMS as an adjuvant intervention approach to facilitate individuals with PD to generalize a learned motor task from one environmental context to another.


Metabolism of cadmium, zinc and copper in the rat kidney: the role of metallothionein and other binding sites.
Studies were undertaken to determine the effect of host zinc deficiency upon the distribution of Cd, Zn and Cu between and within male rat kidney cytosol and unfractionated cell pellet. In the first experiment male rates were fed stock diets supplemented with 100 micrograms Cd/mL in the drinking water for 30 days. Then Cd-treated rats and controls were segregated into groups, which received semipurified diets adequate or deficient in zinc for 14 days. After this regimen there were comparable concentrations of total Cd and metallothionein bound Cd in cytosol and the supernatant of sonicated, unfractionated pellet on a microgram Cd/g protein basis. Although less than 5% of cytosolic Cd is not bound to metallothionein (MT), 3-5 times as much non-MT Cd is present in the particulate fraction. The zinc-deficient (Zn-) dietary regime increases the non-MT Cd in the pellet. Quantitations were done of the Cu and Zn distribution in high molecular weight, superoxide dismutase, and metallothionein regions of the profiles of metals from Sephadex G-75 chromatography. In animals exposed to Cd and fed a zinc-normal (Zn+) diet, supernatant and pellet metal contents only change in the MT fraction. Similarly, zinc deficiency affects primarily the complement of metals bound to metallothionein: zinc is markedly decreased and Cu is lowered to a smaller extent. Cadmium is unchanged. Control kidney, unexposed to Cd, normally contains a substantial amount of Zn,CuMT. Two-week zinc deficiency greatly reduces MT-Zn and -Cu content without altering the metal content of other cellular pools.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986-90) and in the nationwide immunisation program.
Gambian infants were not routinely vaccinated against hepatitis B virus (HBV) before 1986. During 1986-90 the Gambia Hepatitis Intervention Study (GHIS) allocated 125,000 infants, by area, to vaccination or not and thereafter all infants were offered the vaccine through the nationwide immunisation programme. We report HBV serology from samples of GHIS vaccinees and unvaccinated controls, and from children born later. During 2007-08, 2670 young adults born during the GHIS (1986-90) were recruited from 80 randomly selected villages and four townships. Only 28% (753/2670) could be definitively linked to their infant HBV vaccination records (255 fully vaccinated, 23 partially vaccinated [1-2 doses], 475 not vaccinated). All were tested for current HBV infection (HBV surface antigen [HBsAg]) and, if HBsAg-negative, evidence of past infection (HBV core-protein antibody [anti-HBc]). HBsAg-positive samples (each with two age- and sex-matched HBsAg-negative samples) underwent liver function tests. In addition, 4613 children born since nationwide vaccination (in 1990-2007) were tested for HBsAg. Statistical analyses ignore clustering. Comparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy. Among unvaccinated individuals, the prevalence was higher in males (p = 0.015) and in rural areas (p = 0.009), but adjustment for this did not affect estimated vaccine efficacy. Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001. Chronic active hepatitis was not common: the proportion of HBsAg-positive subjects with abnormal liver function tests (ALT > 2 ULN) was 4.1%, compared with 0.2% in those HBsAg-negative. The prevalence of antibodies to hepatitis C virus was low (0.5%, 13/2592). In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990-97, and 0.3% (9/35150) in those born between 1998-2007. Infant HBV vaccination achieves substantial protection against chronic carriage in early adulthood, even though approximately a quarter of vaccinated young adults have been infected. This protection persists past the potential onset of sexual activity, reinforcing previous GHIS findings of protection during childhood and suggesting no need for a booster dose. Nationwide infant HBV vaccination is controlling chronic infection remarkably effectively.


Association between alcohol screening scores and mortality in black, Hispanic, and white male veterans.
Scores on the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire are associated with mortality, but whether or how associations vary across race/ethnicity is unknown. Self-reported black (n = 13,068), Hispanic (n = 9,466), and white (n = 182,688) male Veterans Affairs (VA) outpatients completed the AUDIT-C via mailed survey. Logistic regression models evaluated whether race/ethnicity modified the association between AUDIT-C scores (0, 1 to 4, 5 to 8, and 9 to 12) and mortality after 24 months, adjusting for demographics, smoking, and comorbidity. Adjusted mortality rates were 0.036, 0.033, and 0.054, for black, Hispanic, and white patients with AUDIT-C scores of 1 to 4, respectively. Race/ethnicity modified the association between AUDIT-C scores and mortality (p = 0.0022). Hispanic and white patients with scores of 0, 5 to 8, and 9 to 12 had significantly increased risk of death compared to those with scores of 1 to 4; Hispanic ORs: 1.93, 95% CI 1.50 to 2.49; 1.57, 1.07 to 2.30; 1.82, 1.04 to 3.17, respectively; white ORs: 1.34, 95% CI 1.29 to 1.40; 1.12, 1.03 to 1.21; 1.81, 1.59 to 2.07, respectively. Black patients with scores of 0 and 5 to 8 had increased risk relative to scores of 1 to 4 (ORs 1.28, 1.06 to 1.56 and 1.50, 1.13 to 1.99), but there was no significant increased risk for scores of 9 to 12 (ORs 1.27, 0.77 to 2.09). Post hoc exploratory analyses suggested an interaction between smoking and AUDIT-C scores might account for some of the observed differences across race/ethnicity. Among male VA outpatients, associations between alcohol screening scores and mortality varied significantly depending on race/ethnicity. Findings could be integrated into systems with automated risk calculators to provide demographically tailored feedback regarding medical consequences of drinking.


Cytomegalovirus as an occupational risk in daycare educators.
Cytomegalovirus (CMV) infection continues to be an important occupational risk in the daycare setting. A comprehensive update of scientific evidence is timely to inform and promote appropriate preventive measures. A review of the literature was conducted to examine the evidence for an occupational risk of CMV infection in daycare educators. Sources included Medline, government documents and additional references from published bibliographies. The key words used for searches were 'child day care centres' or 'nurseries' and 'cytomegalovirus' or 'cytomegalovirus infection'. EIGHT CMV SEROPREVALENCE STUDIES ON DAYCARE EDUCATORS IN INDUSTRIALIZED COUNTRIES WERE FOUND: four in the United States, three in Canada and one in Italy. Risk factors for seropositivity were older age, nonwhite race, foreign birth, birth in a low- or middle-income country, diaper changing, having children at home, and a child to educator ratio greater than 6:1 in children 18 to 35 months of age. Risk factors for seroconversion were younger age and working with young children. These studies suggest that daycare centres may be a high-risk setting for CMV infection. Recommendations to prevent CMV infection in this setting include handwashing, selective serological screening, avoiding work with younger children if pregnant and, in some cases, preventive leave from work. Evaluation and expert opinion of the effectiveness of various preventive options for CMV acquisition are needed to ensure that recommendations are evidence-based.


Newly identified bacteriolytic enzymes that target a wide range of clinical isolates of Clostridium difficile.
Clostridium difficile has emerged as a major cause of infectious diarrhea in hospitalized patients, with increasing mortality rate and annual healthcare costs exceeding $3 billion. Since C. difficile infections are associated with the use of antibiotics, there is an urgent need to develop treatments that can inactivate the bacterium selectively without affecting commensal microflora. Lytic enzymes from bacteria and bacteriophages show promise as highly selective and effective antimicrobial agents. These enzymes often have a modular structure, consisting of a catalytic domain and a binding domain. In the current work, using consensus catalytic domain and cell-wall binding domain sequences as probes, we analyzed in silico the genome of C. difficile, as well as phages infecting C. difficile. We identified two genes encoding cell lytic enzymes with possible activity against C. difficile. We cloned the genes in a suitable expression vector, expressed and purified the protein products, and tested enzyme activity in vitro. These newly identified enzymes were found to be active against C. difficile cells in a dose-dependent manner. We achieved a more than 4-log reduction in the number of viable bacteria within 5 h of application. Moreover, we found that the enzymes were active against a wide range of C. difficile clinical isolates. We also characterized the biocatalytic mechanism by identifying the specific bonds cleaved by these enzymes within the cell wall peptidoglycan. These results suggest a new approach to combating the growing healthcare problem associated with C. difficile infections. Biotechnol. Bioeng. 2016;113: 2568-2576. © 2016 Wiley Periodicals, Inc.


Protective Effect of Curcumin and Nanocurcumin on Sperm Parameters and Oxidant-antioxidants System of Rat Testis in Aluminium Phosphide Subacute Poisoning.
Aluminum phosphide (AlP) as an effective pesticide may contribute to oxidative stress and adversely influence sperm parameters. This study aimed to investigate the protective role of curcumin and nanocurcumin on oxidative damage in the testis of rats with AlP toxicity. A total of 42 adult male Wistar rats were equally randomized into the following study groups (n = 7): Control, Control+Curcumin, Control+Nanocurcumin, AlP, AlP+Curcumin, and AlP+Nanocurcumin. The testis tissue was used to investigate the levels of testicular malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and reduced glutathione (GSH) as well as the Catalase (CAT) and superoxide dismutase (SOD) enzyme activity. Epididymal sperm was used to perform sperm analysis. AlP administration led to a significant increase in MDA, and TOS levels and also markedly decreased the SOD activity and the levels of TAC and GSH in testis tissue (p <0.001). Moreover, the motility and viability of sperms were significantly reduced (p <0.001). Curcumin and Nanocurcumin co-administration with AlP remarkably decreased the MDA and TOS level (p <0.001) and significantly increased the GSH and TAC levels as well as the activity of SOD in AlP intoxicated groups (p<0.001). Our findings demonstrated that Nanocurcumin administration has significantly enhanced the sperm quality in AlP intoxicated rats as compared to the control group (p <0.001). According to the results of this study, Curcumin as a potential antioxidant could be an effective attenuative agent against AlP-induced oxidative damage in testis, especially when it is used in encapsulated form, nanocurcumin.


Enhancing the compost maturation of swine manure and rice straw by applying bioaugmentation.
Microorganisms capable of decomposing cellulose, xylan, starch and protein were individually isolated from swine manure compost and soil in this study. The correlations with pH, carbon source concentration, C/N ratio and enzyme activity among these isolated microorganisms were also investigated. Furthermore, the effect of additional inoculation in the compost was studied by measuring variations in the C/N ratio, enzyme activity and compost maturation rate. The inoculated microorganisms used in this study included four bacterial isolates and one commercial microorganism Phanerochaete chrysosporium. The results indicated that the isolated Kitasatospora phosalacinea strain C1, which is a cellulose-degraded microorganism, presented the highest enzyme activity at 31 ℃ and pH 5.5, while the C/N ratio was 0.8%. The isolated xylan-degraded microorganism Paenibacillus glycanilyticus X1 had the highest enzyme activity at 45 ℃ and pH 7.5, while the C/N ratio was 0.5%. The starch-degraded microorganism was identified as Bacillus licheniformis S3, and its highest enzyme activities were estimated to be 31 ℃ and pH 7.5 while the C/N ratio was 0.8%. The highest enzyme activity of the protein-degraded microorganism Brevinacillus agri E4 was obtained at 45 ℃ and pH 8.5, while the C/N ratio was 1.0%. The rate of temperature increase in the compost inoculated with P. chrysosporium was only higher than that of the compost without inoculation, and its compost maturation level was also lower than that of other composts with additional inoculation. The optimal initial C/N ratio of the compost was 27.5 and the final C/N ratio was 18.9. The composting results also indicated that the secondary inoculation would benefit compost maturation, and the lowest final C/N ratio of 17.0 was obtained.


Gender Differences in the Appetite Response to a Satiating Diet.
We examined gender differences in appetite sensations when exposed to Mediterranean diet (MedDiet) meals and determined whether there are gender differences in the change in the satiating properties of the MedDiet over time. Thirty-eight men and 32 premenopausal women consumed a 4-week isoenergetic MedDiet under controlled conditions. Visual analogue scales were used to measure perceived appetite sensations before and immediately after each meal consumed over the course of one day (Wednesday) of the first and the fourth week of intervention. Women reported greater decreases for desire to eat, hunger, and appetite score than men in response to the consumption of the MedDiet meals (gender-by-meal interactions, resp., P = 0.04, P = 0.048, and P = 0.03). Fullness and prospective food consumption responses did not significantly differ between men and women. Between the first and the fourth week of intervention, premeal prospective food consumption increased with time in men (P = 0.0007) but not in women (P = 0.84; P for gender-by-time interaction = 0.04). These results indicate gender differences in appetite sensations when exposed to the MedDiet. These results may be useful in order to have a better understanding of gender issues for body weight management.


[Dabigatran Reversal: A Practical Approach].
Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent reversal of its anticoagulant activity, such as in the case of severe bleeding that is life-threatening; urgent/ emergent surgery or invasive procedures with significant bleeding risk; and the need for thrombolysis in a patient with ischemic stroke, several measures can be taken, including the use of its specific reversal agent, idarucizumab. Based on the guidelines for the use of reversal agents for oral anticoagulants, and on the clinical experience of reversal of dabigatran, a practical guide is presented for use in clinical situations where reversal of dabigatran anticoagulation is required, including the use of idarucizumab. The adoption of this type of guideline contributes to therapeutic optimization and, consequently, greater reversal efficiency and a better resource management.


A structured, segregated model for genetically modified Escherichia coli cells and its use for prediction of plasmid stability.
A structured, segregated model is presented for an asynchronously growing population of genetically modified Escherichia coli cells. A finite representation method was modified so that 272 cells could be used to represent a microbial population. The concept of a "limbo" compartment was introduced to allow random plasmid distribution to daughter cells upon cell division while restricting the number of computer cells included in the calculation. This scheme enabled us to predict plasmid instability and distribution of plasmid-originated properties in a population without a priori determination of growth rates or probability of forming plasmid-free cells from plasmid-containing cells. Predictions of population behavior using a single-cell model requires no adjustable parameters. The results comparing different induction strategies suggest that in continuous culture, there exists an optimum efficiency of partial induction that maximizes the long-term productivity of the gene product due to plasmid stability. With the optimum efficiency of partial induction, constant induction appears to prove more stable than cycling induction.


Microfluidic platforms with monolithically integrated hierarchical apertures for the facile and rapid formation of cargo-carrying vesicles.
We fabricated a simple yet robust microfluidic platform with monolithically integrated hierarchical apertures. This platform showed efficient diffusive mixing of the introduced lipids through approximately 8000 divisions with tiny pores (~5 μm in diameter), resulting in massive, real-time production of various cargo-carrying particles via multi-hydrodynamic focusing.


Severe medication-induced peripheral neuropathy treated with topical doxepin cream in a paediatric patient with leukaemia.
A 17-year-old female with recently relapsed acute lymphoblastic leukaemia and a treatment course complicated by rhinocerebral mucormycosis infection developed severe peripheral neuropathy during the treatment for mucormycosis infection. This was felt to be a medication side effect. Her peripheral neuropathy was refractory to many well-established treatments, but ultimately responded dramatically and consistently to a novel therapy, topical doxepin cream (5%). This case report is the first published report of the application of topical doxepin cream for treatment of peripheral neuropathy in a paediatric patient.


Development of a novel polymer-based carrier for deformable liposomes for the controlled dermal delivery of naringenin.
In recent years, the incidence of skin cancer has increased worldwide, presenting a significant burden on healthcare services. Chemotherapy intervention is often not appropriate for all patients due to localized adverse effects on skin physiology. The aim of this study was, therefore, to consider the development of a novel phytochemical-based deformable liposomal formulation suspended in an aqueous gel for the controlled-release of naringenin. Naringenin is an antioxidant, free radical scavenger, anti-inflammatory agent, and immune system modulator thus may be potentially useful as a pharmacological anti-cancer agent. Formulated liposomes incorporating an increasing loading of Tween 20 (from 0% w/w to 10% w/w) demonstrated a significant decrease in deformability index (DI) (80.71 ± 2.02-59.17 ± 4.42 %), indicating an increase in elasticity. The release of naringenin over 24 h was directly affected by Tween-20 concentration, decreasing from 100.72%±4.98% to 79.53%±3.68% for 0% and 2% w/w Tween 20, respectively. Further, the incorporation of deformable liposomes into hydroxyethylcellulose (HEC) and hydroxypropyl methylcellulose (HPMC) gels resulting in a further retardation of naringenin release, 23.21%±1.17% and 19.83%±1.50%, respectively, over 24 h. Incubation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-loaded liposomes with human dermal fibroblast (HDF) and keratinocyte cells demonstrated intracellular accumulation within 2 h, confirming deformable liposomes may be beneficial in improving drug penetration across dermal cells and would be valuable in emerging controlled-release formulations.


Cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a New Zealand white rabbit (Oryctolagus cuniculus).
Pituitary adenoma in a rabbitA 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit.


The impact of parents' physical activity goals and parental attitudes on physical activity during leisure time among children in middle childhood.
Parents' supportiveness and health-promoting habits significantly affect the intensity of children's physical activity (PA) and the involvement of parents in their engagement in PA; in this domain, both the hours devoted to PA and PA goals can be assessed. The family plays an important role in shaping the physical and social organization of the environment for children aged 4-6 years. A total of 680 families with 5-year-old children (330 girls, 350 boys) took part in the study. Data were collected from these participants, who were recruited from preschools and primary schools in the Pomeranian region of Poland. The aim of this study was to determine whether the involvement of parents in PA mediates the influence of parental attitudes on the ways in which their children spend their leisure time. The results showed that not all parental attitudes had direct impact on children's leisure time in PA and outside PA. Other aspects parental attitude had no significant impact on offspring's free time. Among fathers, only four aspects of parental attitude (namely, acceptance-rejection, inconsistency, autonomy, and overprotectiveness) had an impact on PA goals. Mothers' goals were influenced by the strength of a larger number of aspects of attitude (namely, acceptance-rejection, autonomy, inconsistency, over-demandingness, and overprotectiveness). Similarly, the strength of mothers' and fathers' acceptance-rejection attitudes, attitudes of autonomy, and overprotectiveness had an impact on their PA goals but were not directly linked to their children's leisure-time engagement in PA. Not all parental attitudes have a direct impact on children's PA or non-PA leisure time. However, the goals of PA parents have been recognized influence the leisure time of children in PA and outside PA. The most statistically significant relationship for both mothers and fathers was between parental attitudes and PA goals. Parental attitudes do not play a significant role in explaining involvement in PA or lack of it in leisure time among 5-year-old children.


Determination of size distributions of non-spherical pores or particles from single x-ray phase contrast images.
Although x-ray tomography is commonly used to characterize the three-dimensional structure of materials, sometimes this is impractical due either to limited time for data collection (such as in rapidly-evolving systems) or the need to limit the radiation exposure of the sample. In such situations, it is desirable to extract as much information as possible from a more limited data set. In this paper, we describe how to extract the size distribution of non-spherical pores (or, equivalently, particles) from single x-ray phase contrast imaging (XPCI). Because the pores overlap in projection, interpreting the images and extracting quantitative information about the size distribution is non-trivial. In this paper we extend a previously-developed Fourier-based framework for interpreting the speckle pattern of XPCI images from materials with spherical pores to the more challenging case of non-spherical pores. We develop an analytical expression for the XPCI image from a distribution of randomly-oriented ellipsoidal pores, and show that we can use this expression to extract quantitative information about the size distribution from single images. We discuss three approaches to evaluating this expression, corresponding to different assumptions about the nature of the size distribution, and validate our results with simulated XPCI images and experimental data from Berea sandstone.


Proliferative nodules of undifferentiated spindle cells arising in a large congenital melanocytic naevus.
Proliferative nodules (PN) are benign lesions that arise in large congenital melanocytic naevi (LCMN). Clinically and histologically they can be difficult to differentiate from malignancies, which are also associated with LCMN. The PN in this case consisted of undifferentiated spindle cells and exhibited unusual histological features including negative stains for melanocytic markers (S100, HMB45 and MelA), negative stain for c-Kit, high mitotic index and unusual morphology of the lesional cells. As a result, a firm histological classification could not be made, which posed a challenge for the clinical management.


A versatile program for the calculation of linear accelerator room shielding.
This work aims at designing a computer program to calculate the necessary amount of shielding for a given or proposed linear accelerator room design in radiotherapy. The program (Shield Calculation in Radiotherapy, SCR) has been developed using Microsoft Visual Basic. It applies the treatment room shielding calculations of NCRP report no. 151 to calculate proper shielding thicknesses for a given linear accelerator treatment room design. The program is composed of six main user-friendly interfaces. The first enables the user to upload their choice of treatment room design and to measure the distances required for shielding calculations. The second interface enables the user to calculate the primary barrier thickness in case of three-dimensional conventional radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT) and total body irradiation (TBI). The third interface calculates the required secondary barrier thickness due to both scattered and leakage radiation. The fourth and fifth interfaces provide a means to calculate the photon dose equivalent for low and high energy radiation, respectively, in door and maze areas. The sixth interface enables the user to calculate the skyshine radiation for photons and neutrons. The SCR program has been successfully validated, precisely reproducing all of the calculated examples presented in NCRP report no. 151 in a simple and fast manner. Moreover, it easily performed the same calculations for a test design that was also calculated manually, and produced the same results. The program includes a new and important feature that is the ability to calculate required treatment room thickness in case of IMRT and TBI. It is characterised by simplicity, precision, data saving, printing and retrieval, in addition to providing a means for uploading and testing any proposed treatment room shielding design. The SCR program provides comprehensive, simple, fast and accurate room shielding calculations in radiotherapy.


CRISPR Cas9-guided chromatin immunoprecipitation identifies miR483 as an epigenetic modulator of IGF2 imprinting in tumors.
The normally imprinted insulin-like growth factor II (IGF2) gene is aberrantly upregulated in a variety of human malignancies, yet the mechanisms underlying this dysregulation are still poorly defined. In this report, we used a CRISPR Cas9-guided chromatin immunoprecipitation assay to characterize the molecular components that participate in the control of IGF2 gene expression in human tumor cells. We found that miR483, an oncogenic intronic miRNA, binds to the most upstream imprinted IGF2 promoter, P2. Ectopic expression of miR483 induced upregulation of IGF2 expression, in parallel with an increase in tumor cell proliferation, migration, invasion, and tumor colony formation. miR483 induced loss of IGF2 imprinting by altering the epigenotype at P2, with reduction in histone H3K27 methylation and a decrease in chromatin binding of two imprinting regulatory factors, CTCF and SUZ12. This study identifies a new role for miR483 in the regulation of IGF2 gene expression through the alteration of the promoter epigenotype.


Babesia canis infection in a splenectomized dog.
The present report describes a fatal case of non-experimental babesiosis in a splenctomized 3-year-old fox terrier. A very intense parasitaemia including clusters of up to 16 Babesiae and a prominent haemophagocytic activity were the most relevant findings. A marked leukocytosis, thrombocytopenia and regenerative anaemia were observed. Despite prompt treatment with babesiacidal compounds the condition progressed to acute renal failure and resulted in the death of the animal 48 hours after the onset of symptoms.


Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy.
Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN.


Structure-Based de Novo Molecular Generator Combined with Artificial Intelligence and Docking Simulations.
Recently, molecular generation models based on deep learning have attracted significant attention in drug discovery. However, most existing molecular generation models have serious limitations in the context of drug design wherein they do not sufficiently consider the effect of the three-dimensional (3D) structure of the target protein in the generation process. In this study, we developed a new deep learning-based molecular generator, SBMolGen, that integrates a recurrent neural network, a Monte Carlo tree search, and docking simulations. The results of an evaluation using four target proteins (two kinases and two G protein-coupled receptors) showed that the generated molecules had a better binding affinity score (docking score) than the known active compounds, and the generated molecules possessed a broader chemical space distribution. SBMolGen not only generates novel binding active molecules but also presents 3D docking poses with target proteins, which will be useful in subsequent drug design. The code is available at https://github.com/clinfo/SBMolGen.


[Approach and efficacy of endovascular repair for abdominal aortic aneurysm with hostile proximal landing zone].
To explore the option and efficacy of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) with hostile aortic proximal landing anatomy. The clinical data of 51 AAA patients with hostile aortic proximal landing anatomy treated by EVAR from January 2010 to June 2012 at our hospital was retrospectively analyzed. There were 44 males and 7 females with a mean age of 73 years (range: 42 - 94). The anatomic measurements included a diameter of aneurysm body 32 - 100 mm, a length of proximal neck 0 - 50 mm, a width of proximal neck 15 - 40 mm and infrarenal angulation 15 - 80 degrees. In addition, there were calcification (n = 10) and thrombus lining with aortic neck (n = 15) and irregular shape of aortic neck (n = 5) respectively. The stent-grafts were deployed by 4 femoral arteries. Many types of aortic stent were used, such as Endurant (n = 9), Talent (n = 5), Zenith (n = 31), Hercules (n = 5), Palmaz/CUFF (n = 6) and multilayer bare-stent (n = 2). And 11 patients underwent fenestrated EVAR and 31 with chimney EVAR involving renal artery (39 branches), superior mesenteric artery (3 branches) and celiac trunk (3 branches). The primary technical success rate was 100%. The perioperative endoleak rate was 17.6%. During the mean follow-up period of 13 months (2 - 28), the primary patency of stent was 96.1% and the thrombus rate of aneurysm 82.4%. Two cases of new endoleak and 3 cases of residual endoleak underwent secondary intervention. In addition, long-term follow-up was required for 3 patients with stent-graft migration (< 10 mm). There was no case of death, infection, occlusions, ischemia of lower limbs, aneurysm expansion or rupture. A variety of EVAR options are both safe and efficacious in the treatment of AAA with hostile proximal landing zone.


DNA affects the composition of lipoplex protein corona: a proteomics approach.
The distribution of drug delivery systems into the body is affected by plasma proteins adsorbed onto their surface. Furthermore, an exact understanding of the structure and morphology of drug carriers is fundamental to understand their role as gene delivery systems. In this work, the adsorption of human plasma proteins bound to cationic liposomes and to their relative DNA lipoplexes was compared. A shotgun proteomics approach based on HPLC coupled to high resolution MS was used for an efficient identification of proteins adsorbed onto liposome and lipoplex surfaces. The distinct pattern of proteins adsorbed helps to better understand the DNA compaction process. The experimental evidence leads us to hypothesize that polyanionic DNA is associated to the lipoplex surface and can interact with basic plasma proteins. Such a finding is in agreement with recent results showing that lipoplexes are multilamellar DNA/lipid domains partially decorated with DNA at their surface. Proteomics experiments showed that the lipoplex corona is rich of biologically relevant proteins such as fibronectin, histones and complement proteins. Our results provide novel insights to understand how lipoplexes activate the immune system and why they are rapidly cleared from the blood stream. The differences in the protein adsorption data detected in the presented experiments could be the basis for the establishment of a correlation between protein adsorption pattern and in vivo fate of intravenously administered nanoparticles and will require some consideration in the future.


45,XO Turner's syndrome without evidence of mosaicism in a patient with two pregnancies.
A case of Turner's syndrome (45,XO) with two pregnancies is reported. There was no evidence of mosaicism after chromosomal investigation of 5 different tissues (2 ovaries, blood, skin, uterus). Pregnancy occurred in both cases after withdrawal of substitutional hormone therapy. The first pregnancy ended with abortion of a macerated hydrocephalic female fetus. Chromosome studies could not be carried out. The second pregnancy ended with delivery by caesarian section of a normal boy (46,XY). Prenatal chromosome analysis was not carried out for ethical reasons.


Formation of NiCo2 V2 O8 Yolk-Double Shell Spheres with Enhanced Lithium Storage Properties.
Complex nanostructures with multi-components and intricate architectures hold great potential in developing high-performance electrode materials for lithium-ion batteries (LIBs). Herein, we demonstrate a facile self-templating strategy for the synthesis of metal vanadate nanomaterials with complex chemical composition of NiCo2 V2 O8 and a unique yolk-double shell structure. Starting with the Ni-Co glycerate spheres, NiCo2 V2 O8 yolk-double shell spheres are synthesized through an anion-exchange reaction of Ni-Co glycerate templates with VO3- ions, followed by an annealing treatment. By virtue of compositional and structural advantages, these NiCo2 V2 O8 yolk-double shell spheres manifest outstanding lithium storage properties when evaluated as anodes for LIBs. Impressively, an extra-high reversible capacity of 1228 mAh g-1 can be retained after 500 cycles at a high current density of 1.0 Ag-1 .