Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread.
BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 10(5.7) plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue.


Peers as clinicians: Examining the impact of Stay Play Talk on social communication in young preschoolers with autism.
Peer Mediated Interventions (PMIs) can be incorporated into integrated early childhood and preschool settings to address socialization impairments observed in children with ASD (Katz & Girolametto, 2013). However, research examining specific PMI strategies with young preschoolers remains limited. The current study examines the efficacy of the Stay, Play, Talk PMI (English, Shafer, Goldstein, & Kaczmerek, 1997) on the social communication skills of young preschool children diagnosed with an Autism Spectrum Disorder (ASD). Each of 3 typically developing children (ages 3-5 years) was paired with a child with an ASD (ages 3-4 years). Typically developing peers were taught to Stay with their friend, Play with their friend, and Talk to their friend. The child dyads played together during two, 20-min weekly sessions for 6-8 weeks. A multiple baseline design across participants was implemented to measure the impact of the Stay Play Talk strategies on social initiations and responses characterized by non-coordinated gestures, gestures, and words. Simulation Modeling Analysis was also conducted to confirm visual analysis. All 3 typical peer buddies and all 3 target children with ASD demonstrated increases in the frequency of their responses, reaching levels that greatly exceeded baseline levels. Further, social reciprocations increased among each dyad above baseline. Social initiations remained variable across dyads. Gains were not maintained two months post intervention. Results of this study corroborated previous findings that support the usefulness of PMIs to improve social communication of young children with ASD (Chan et al., 2009) and suggest an economical, naturally occurring approach to improve social communication during early childhood. Readers will gain knowledge regarding the social communication profile of children with ASD and how this profile can negatively impact language development and peer relationships. In addition, readers will be able to identify the basic components of the Stay Play Talk intervention. Finally, this paper will explain the impacts of the Stay Play Talk intervention on the social communication skills of young children with ASD.


Stimulation of the myelin basic protein gene expression by 9-cis-retinoic acid and thyroid hormone: activation in the context of its native promoter.
Thyroid hormone plays an important role in brain development, in part by regulating myelination. Previous studies have shown that the myelin basic protein (MBP) promoter is activated by thyroid hormone (T3) via a T3-response element (T3RE) at position -186. Surprisingly, although MBP levels are initially decreased in hypothyroid neonates, they approach later control levels, in most brain regions, despite persistent hypothyroidism. We have studied the T3-independent transcriptional regulation of this gene, using transient transfection assays. We found that, in the absence of T3, the RXR ligand, 9-cis-retinoic acid (9cRA) was able to stimulate transcription of the MBP promoter in a dose-dependent manner. This activation was unaffected by the mutation or deletion of the T3RE and required DNA sequences located between positions -162/+60. Accordingly, this MBP promoter fragment bound RXR in vitro. The 9cRA-dependent activation of the MBP promoter required the presence of both, the DNA binding and the ligand-dependent transactivation domain (AF-2) in RXR. Furthermore, as T3, 9cRA was able to stimulate MBP expression in the CG-4 cell line after differentiation to oligodendrocytes and increased the number of cells expressing the MBP protein in primary rat optic nerve glial cell cultures.


Purification and biochemical characterization of a halotolerant Staphylococcus sp. extracellular lipase.
We have isolated a lipolytic halotolerant bacterium, designated as CJ3, that was identified as a Staphylococcus sp. Culture conditions were optimized and the highest extracellular lipase production amounting to 5 U/ml was achieved after 24 h of cultivation. The extracellular lipase was purified 24-fold by ammonium sulfate precipitation and a Sephacryl S-200 chromatography, and its molecular mass was found to be around 38 kDa, as revealed by SDS-PAGE and gel filtration. The lipase substrate specificity was investigated using short (tributyrin) and long (olive oil) chain triglyceride substrates. The lipase was inhibited by submicellar concentrations of Triton X-100, and maximum specific activities were found to be 802 U/mg on tributyrin and 260 U/mg on olive oil at pH 8.0 and 45 °C. The lipase was fairly stable in the pH range from 6.0 to 9.0, and about 69% of its activity was retained after incubation at 45 °C for 60 min. The enzyme showed a high tolerance to a wide range of salt concentration and a good stability in organic solvents, especially in long-chain alcohols.


Gene analysis of Epstein-Barr virus-associated lymphomas in Hu-Pbl/SCID chimeras.
The mechanisms of Epstein-Barr virus (EBV)-associated tumor development are incompletely understood. The aim of this study was to investigate the gene expression of EBV-associated lymphomas in hu-PBL/SCID mice. Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were transplanted into severe combined immunodeficiency (SCID) mice. In situ hybridization was used to detect EBV-encoded small RNA- 1 (EBER1) in tumor tissues. Mutation of TP53 exons 5-8 in EBV-induced lymphomas was analyzed by PCR-SSCP. Immunohistochemical staining was used to examine EBV gene products and cellular oncoproteins. Twenty-one of 29 mice developed tumors. EBER1 was positive in the nuclei of almost all tumor cells. Immunohistochemistry showed positive staining of LMP1, EBNA2 and ZEBRA in a small number of tumor cells. Immunohistochemically detectable p53 protein expression was common (85.7%), but TP53 gene mutations were identified in only four cases (19.1%) of EBV-associated lymphomas. Positivity rates of C-myc, Bcl-2 and Bax expression were 100%, 95.2%, and 90.5%, respectively, in the 21 cases of EBV-associated lymphomas. Our preliminary findings suggest that EBV-associated lymphomas in hu-PBL/SCID chimeras show EBV infection, expression of oncogenic viral genes, and overexpression of cellular oncogenes. TP53 gene mutations are rare but p53 protein is commonly expressed in EBV-associated lymphomas.


Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic-fMRI study.
The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia.


miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.
Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.


Safety of pregnancy in acromegaly patients and maternal and infant outcomes after pregnancy: single-center experience from China and review of the literature.
Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature. An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities. Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4-10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001). Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.


Biomarkers for predicting central neuropathic pain occurrence and severity after spinal cord injury: results of a long-term longitudinal study.
Central neuropathic pain (CNP) after spinal cord injury (SCI) is debilitating and immensely impacts the individual. Central neuropathic pain is relatively resistant to treatment administered after it develops, perhaps owing to irreversible pathological processes. Although preemptive treatment may overcome this shortcoming, its administration necessitates screening patients with clinically relevant biomarkers that could predict CNP early post-SCI. The aim was to search for such biomarkers by measuring pronociceptive and for the first time, antinociceptive indices early post-SCI. Participants were 47 patients with acute SCI and 20 healthy controls. Pain adaptation, conditioned pain modulation (CPM), pain temporal summation, wind-up pain, and allodynia were measured above, at, and below the injury level, at 1.5 months after SCI. Healthy control were tested at corresponding regions. Spinal cord injury patients were monitored for CNP emergence and characteristics at 3 to 4, 6 to 7, and 24 months post-SCI. Central neuropathic pain prevalence was 57.4%. Central neuropathic pain severity, quality, and aggravating factors but not location somewhat changed over 24 months. Spinal cord injury patients who eventually developed CNP exhibited early, reduced at-level pain adaptation and CPM magnitudes than those who did not. The best predictor for CNP emergence at 3 to 4 and 7 to 8 months was at-level pain adaptation with odds ratios of 3.17 and 2.83, respectively (∼77% probability) and a cutoff value with 90% sensitivity. Allodynia and at-level CPM predicted CNP severity at 3 to 4 and 24 months, respectively. Reduced pain inhibition capacity precedes, and may lead to CNP. At-level pain adaptation is an early CNP biomarker with which individuals at risk can be identified to initiate preemptive treatment.


Cognitive, Genetic, Brain Volume, and Diffusion Tensor Imaging Markers as Early Indicators of Dementia.
Although associated with dementia and cognitive impairment, microstructural white matter integrity is a rarely used marker of preclinical dementia. We aimed to evaluate the individual and combined effects of multiple markers, with special focus on microstructural white matter integrity, in detecting individuals with increased dementia risk. A dementia-free subsample (n = 212, mean age = 71.33 years) included in the population-based Swedish National Study on Aging and Care (SNAC-K) underwent magnetic resonance imaging (T1-weighted, fluid-attenuated inversion recovery, diffusion tensor imaging), neuropsychological testing (perceptual speed, episodic memory, semantic memory, letter and category fluency), and genotyping (APOE). Incident dementia was assessed during six years of follow-up. A global model (global cognition, APOE, total brain tissue volume: AUC = 0.920) rendered the highest predictive value for future dementia. Of the models based on specific markers, white matter integrity of the forceps major tract was included in the most predictive model, in combination with perceptual speed and hippocampal volume (AUC = 0.911). Assessment of microstructural white matter integrity may improve the early detection of dementia, although the added benefit in this study was relatively small.


[Critical period in the work of the form-inducing apparatus of the lens in chick embryos, detected after chloramphenicol application].
The inhibitor of protein synthesis chloramphenicol (2 mg/egg) was applied to elucidate the critical period in the chicken lens development. Chloramphenicol injected before incubation and at 24, 30 and 48 h of incubation did not prevent the formation of parts in the lens-inducing apparatus (the optic vesicle, and the presumptive lens ectoderm), but the injection at the stage of 24--30 h of incubation resulted, in many survived for 5--7 days of incubation, in lack of the lens. Therefore, it is possible to speak about a disturbance in the activity of the inducing apparatus during the period of determination, or about a critical period of the lens development.


Universal machine-learning algorithm for predicting adsorption performance of organic molecules based on limited data set: Importance of feature description.
Adsorption of organic molecules from aqueous solution offers a simple and effective method for their removal. Recently, there have been several attempts to apply machine learning (ML) for this problem. To this end, polyparameter linear free energy relationships (pp-LFERs) were employed, and poor prediction results were observed outside model applicability domain of pp-LFERs. In this study, we improved the applicability of ML methods by adopting a chemical-structure (CS) based approach. We used the prediction of adsorption of organic molecules on carbon-based adsorbents as an example. Our results show that this approach can fully differentiate the structural differences between any organic molecules, while providing significant information that is relevant to their interaction with the adsorbents. We compared two CS feature descriptors: 3D-coordination and simplified molecular-input line-entry system (SMILES). We then built CS-ML models based on neural networks (NN) and extreme gradient boosting (XGB). They all outperformed pp-LFERs based models and are capable to accurately predict adsorption isotherm of isomers with similar physiochemical properties such as chiral molecules, even though they are trained with achiral molecules and racemates. We found for predicting adsorption isotherm, XGB shows better performance than NN, and 3D-coordinations allow effective differentiation between organic molecules.


An abundant LEA protein in the anhydrobiotic midge, PvLEA4, acts as a molecular shield by limiting growth of aggregating protein particles.
LEA proteins are found in anhydrobiotes and are thought to be associated with the acquisition of desiccation tolerance. The sleeping chironomid Polypedilum vanderplanki, which can survive in an almost completely desiccated state throughout the larval stage, accumulates LEA proteins in response to desiccation and high salinity conditions. However, the biochemical functions of these proteins remain unclear. Here, we report the characterization of a novel chironomid LEA protein, PvLEA4, which is the most highly accumulated LEA protein in desiccated larvae. Cytoplasmic-soluble PvLEA4 showed many typical characteristics of group 3 LEA proteins (G3LEAs), such as desiccation-inducible accumulation, high hydrophilicity, folding into α-helices on drying, and the ability to reduce aggregation of dehydration-sensitive proteins. This last property of LEA proteins has been termed molecular shield function. To further investigate the molecular shield activity of PvLEA4, we introduced two distinct methods, turbidity measurement and dynamic light scattering (DLS). Turbidity measurements demonstrated that both PvLEA4, and BSA as a positive control, reduced aggregation in α-casein subjected to desiccation and rehydration. However, DLS experiments showed that a small amount of BSA relative to α-casein increased aggregate particle size, whereas PvLEA4 decreased particle size in a dose-dependent manner. Trehalose, which is the main heamolymph sugar in most insects but also a protectant as a chemical chaperone in the sleeping chironomid, has less effect on the limitation of aggregate formation. This analysis suggests that molecular shield proteins function by limiting the growth of protein aggregates during drying and that PvLEA4 counteracts protein aggregation in the desiccation-tolerant larvae of the sleeping chironomid.


Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients.
Invasive aspergillosis (IA) is an important cause of mortality in critically ill patients, but the diagnosis is difficult as clinical and radiological signs are neither sensitive nor specific. Serum galactomannan (GM) is a useful marker for IA, but exhibits low sensitivity in non-neutropenic patients. In our previous work, strong antibody reactivity to thioredoxin reductase of Aspergillus fumigatus was found in non-neutropenic IA patients. Using recombinant thioredoxin reductase GliT (TR), an antigenic protein secreted by A. fumigatus, as the coating antigen, an enzyme-linked immunosorbent assay (ELISA) for detecting anti-TR antibodies was developed. The antibody response to TR in IA animal models and 42 non-neutropenic patients with culture- and/or histology-documented IA was investigated. The results showed that anti-TR antibody was detectable in rabbit serum 7-9 days after exposure to the fungus. The sensitivity and specificity of the anti-TR antibody assay in patients were 80.9% and 96%, respectively, while the sensitivity of GM in this group of patients was only 52.3%. The specificity of the assay was confirmed by testing the sera from patients infected with other pathogenic fungal species and bacteria.


Effect of Structural Parameters on the Polarizabilities of Methanol Clusters: A Hirshfeld Study.
The polarizabilities of fifty methanol clusters (CH3OH)n, n = 1 to 12, were calculated at the B3LYP/6-311++G** level of theory and partitioned into molecular contributions using the Hirshfeld-I method. The resulting molecular polarizabilities were found to be determined by the polarizabilities of the two parts of the molecule, the hydrophilic hydroxyl group and the hydrophobic methyl group, each exhibiting a different dependency upon the local environment. The polarizability of the hydroxyl group was found to be dependent on the number, type, and strength of the hydrogen bonds a methanol molecule makes, whereas the polarizability of the methyl groups is mostly influenced by sterical hindrance. The findings were compared with the results obtained in a previous study on water clusters. The influence of the BSSE correction was investigated and found to increase polarizability values by up to 8.5%.


Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers.
Fexofenadine is a selective, nonsedating H1-receptor antagonist that relieves symptoms of allergic conditions. Two randomized, double-blind, parallel-group, placebo-controlled dose-escalation studies were performed in healthy men to determine the maximum tolerated oral dose, pharmacokinetics, pharmacodynamics, and safety of fexofenadine hydrochloride. In the first study, 87 subjects (6 in the active drug group and 2 in the placebo group) received single oral doses of fexofenadine hydrochloride ranging from 10 to 800 mg or placebo. In the second study, 32 subjects (3 in the active drug group and 1 in the placebo group) received multiple fexofenadine hydrochloride doses ranging from 20 to 690 mg or placebo twice daily for 28 1/2 days. Serial plasma and urine samples were collected. Fexofenadine concentrations were determined by HPLC and fluorescence. Wheal and flare response to intradermal histamine was used to evaluate antihistaminic activity. Fexofenadine hydrochloride was rapidly absorbed, reaching peak concentrations in 0.83 to 1.33 hours. Single-dose mean concentration ranged from 46 to 6383 ng/mL, and steady-state maximum plasma concentration ranged from 58 to 4677 ng/mL. Mean area under the plasma concentration-time curve was approximately proportional to dose. Oral clearance, renal clearance, and cumulative percent of drug excreted in urine were similar after single and multiple doses and were generally constant over the dose range studied. Inhibition of skin wheal and flare was shown for single doses of 40 mg and higher and for all multiple doses. No fexofenadine dose-related trends or apparent differences from placebo were found for any safety parameter. Fexofenadine hydrochloride was well tolerated at oral doses up to 11 times the recommended therapeutic dose. In addition, fexofenadine hydrochloride showed significant antihistaminic activity and dose-proportional pharmacokinetics over a wide dosing range.


Fragment-based target screening as an empirical approach to prioritising targets: a case study on antibacterials.
Here, we describe a novel workflow combining informatic and experimental approaches to enable evidence-based prioritising of targets from large sets in parallel. High-throughput protein production and biophysical fragment screening is used to identify those targets that are tractable and ligandable. As proof of concept we have applied this to a set of antibacterial targets comprising 146 essential genes. Of these targets, 51 were selected and 38 delivered results that allowed us to rank them by ligandability. The data obtained against these derisked targets have enabled rapid progression into structurally enabled drug discovery projects, demonstrating the practical value of the fragment-based target screening workflow.


Evolution of functional tissue engineering for tendon and ligament repair.
This review paper is motivated by a Back-to-Basics presentation given by the author at the 2022 Orthopaedic Research Society meeting in Tampa, Florida. I was tasked with providing a brief history of research leading up to the introduction of functional tissue engineering (FTE) for tendon and ligament repair. Beginning in the 1970s, this timeline focused on two common orthopedic soft tissue problems, anterior cruciate ligament ruptures in the knee and supraspinatus tendon injuries in the shoulder. Historic changes in the field over the next 5 decades revealed a transformation from a focus more on mechanics (called "bioMECHANICS") on a larger (tissue) scale to a more recent focus on biology (called "mechanoBIOLOGY") on a smaller (cellular and molecular) scale. Early studies by surgeons and engineers revealed the importance of testing conditions for ligaments and tendons (e.g., high strain rates while avoiding subject disuse and immobility) and the need to measure in vivo forces in these tissues. But any true tissue engineering and regeneration in these early decades was limited more to the use of auto-, allo- and xenografts than actual generation of stimulated cell-scaffold constructs in culture. It was only after the discovery of tissue engineering in 1988 and the recognition of frequent rotator cuff injuries in the early 1990s, that biologists joined surgeons and engineers to discover mechanical and biological testing criteria for FTE. This review emphasizes the need for broader and more inclusive collaborations by surgeons, biologists and engineers in the short term with involvement of those in biomaterials, manufacturing, and regulation of new products in the longer term.


Percentage of Impervious Surface Soil as Indicator of Urbanization Impacts in Neotropical Aquatic Insects.
Several recent studies have shown a strong correlation between the area of impervious surface soil (IS) and the insect community structure from urban streams. This study assessed whether this relationship is observed in Neotropical streams. We examined if an increased IS reduces the diversity and simplifies the trophic structure of the community of Ephemeroptera, Plecoptera, and Trichoptera. An IS threshold was detected between 1.6 and 9.3%, in which there is a change in the community, both in taxonomic richness and trophic structure. Among the 27 genera identified, only 15 occurred in streams with IS > 9%, while 24 genera were registered in streams with IS < 2%. The trophic guilds of predators and shredders were not observed in streams with high IS, decreasing the number of guilds in these streams from 5 to 3, compared with the streams with low IS. Three hypotheses with cumulative effect have been proposed to explain such variations. Based on the IS threshold verified, the creation of a mosaic of land use, where some subbasins would be sacrificed and others would be preserved, was suggested as a mitigation measure for the impacts caused by urbanization in the Neotropical aquatic insects' fauna.


Development and calibration of a method for direct measurement of 220Rn (thoron) activity concentration.
The interest in the measurement of thoron (220Rn) activity concentration in air has recently increased, with the attention for the development of standards useful for the calibration of measuring instruments. Due to its short half-life (55.8 s), consolidated techniques for the realization and the use of controlled atmospheres of radon (222Rn) are not effective in the case of thoron. New adequate methodology are required. A method for the measurement of the thoron reference activity based on the direct detection of the alpha particles produced by the decay of 220Rn, from natural samples containing 232Th, is here proposed. The possibility of observing an acceptable spectrum is entrusted to the realization of measurement chambers small enough to reduce as much as possible the energy loss of the alpha particles before they reach the Silicon detector. Such a chamber was realized and used with a known thoron atmosphere in a controlled environment. The experimental results are compared with those obtained from the simulation with the Monte Carlo method: (i) the alpha spectra coming directly from thoron atoms exhibit similar shape with a linear trend plus an exponential trend on the left side of the 220Rn peak, depending from the distance between source and detector; (ii) the corresponding 220Rn detection efficiency values are compatible considering the uncertainties. An investigation was conducted to study the shape of the 220Rn spectra vs the different volume of chambers, through Monte Carlo simulations. The results show: (i) the linear part of the spectra shape goes to reduce with the increasing of the height of the chamber; (ii) the 220Rn detection efficiency decreases with the increasing of the height of the chamber.


Real-Life Population Pharmacokinetics of Recombinant Factor XIII and Dosing Considerations for Preventing the Risk of Bleeding in Patients with FXIII Congenital Deficiency.
Recombinant factor XIII (rFXIII) at the recommended dosage of 35 IU/kg every 4 weeks is currently used for prophylaxis of bleeding in patients affected by FXIII deficiency. The aim of this study was to describe the population pharmacokinetics of rFXIII in patients with FXIII deficiency being treated with rFXIII in real-life and to assess, using Monte Carlo simulations, the attainment of defined FXIII concentration thresholds associated with prevention of the risk of bleeding over time. A nonlinear mixed-effects model approach was used for population analysis. Monte Carlo simulations were used to generate 10,000 FXIII concentration-time profiles associated with incremental doses of 25, 30, 35, 40, 45 and 50 IU/kg of rFXIII. The probability of target attainment (PTA) of FXIII concentrations at thresholds of > 0.05, > 0.10 and > 0.15 IU/mL were calculated weekly, from days 7 to 49. A total of 18 patients provided 99 FXIII concentrations; most patients (77.8%, 14/18) had severe FXIII deficiency. A two-compartment pharmacokinetic model with linear elimination from the central compartment best described rFXIII data. No covariates were associated with rFXIII disposition. Pharmacokinetic parameter estimates were 0.16 mL/h/kg for clearance, 57.35 mL/kg for volume of distribution at steady-state, and 11.72 days for elimination half-life. The standard 35 IU/kg dose resulted in PTAs of the pharmacodynamic thresholds of FXIII concentrations of > 0.05, > 0.10 and > 0.15 IU/mL at day 28 that were equal to 89.9%, 68.9% and 47.8%, respectively. Intensive FXIII monitoring from day 14, and/or shortening the dosing interval between rFXIII administrations, should be considered to minimise the risk of bleeding.


High mobility group 1 and 2 proteins bind preferentially to DNA that contains bulky adducts induced by benzo[a]pyrene diol epoxide and N-acetoxy-acetylaminofluorene.
High mobility group (HMG) proteins 1 and 2 are abundant non-histone chromosomal proteins that bind preferentially DNA that is bent or underwound. Previous studies have shown that these proteins preferentially bind to DNA damaged by the crosslinking agents cis-diammine-dichloro-platinum(II), chromium(III) and UV-C radiation. Here we have studied the binding of HMG-1/2 proteins to a duplex oligonucleotide damaged by benzo(a)pyrene diol epoxide or N-acetoxy-acetylaminofluorene using an electrophoretic mobility shift assay. Both chemicals induce monoadducts that are known to distort DNA structure. The affinities of HMG-1/2 for DNA damaged by benzo[a]pyrene diol epoxide or N-acetoxy-acetylaminofluorene were similar to that for UV-irradiated DNA, which were an order of magnitude higher than for undamaged DNA. In contrast, DNA modified by dimethyl sulfate was not preferentially recognised by HMG-1/2.


Evaluation of the relationship of neutrophil-to lymphocyte ratio and platelet-to-lymphocyte ratio with in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has the highest mortality rate and medical costs. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio are inflammatory markers that have been recently linked to the AECOPD severity and patient outcome. Therefore, the present study aimed at evaluating the diagnostic value of NLR and PLR in the prognosis of the in-hospital mortality in AECOPD patients. The present retrospective study was performed on 829 AECOPD patients. Age, gender and laboratory results of CBC tests including lymphocyte count, neutrophil count, platelet count, hemoglobin count, white blood cell count (WBC), eosinophil cell count, NLR, PLR and CRP as well as the mortality data were collected from the patients' records and subsequently recorded. The results of the present study revealed that NLR with the cut-off value of 6.90, sensitivity of 60.87%, and specificity of 73.29% had a significant diagnostic value in the prognosis of in-hospital mortality in AECOPD patients (P < 0.05). A similar significant finding regarding the diagnostic value in the prognosis of in-hospital mortality in AECOPD patients was obtained for CRP with the cut-off value of 30, sensitivity of 73.08%, and specificity of 60.26% (P < 0.05). However, the diagnostic value of PLR in the prognosis of in-hospital mortality in AECOPD patients was found to be insignificant (P = 0.18). According to the results of the present study, NLR > 6.90 can be considered as a valuable and accurate marker in the prognosis of in-hospital mortality in AECOPD patients.


Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach.
The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches-maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)-as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.


3D/4D Reconstruction and Quantitative Total Body Imaging.
Total-body PET image reconstruction follows a similar procedure to the image reconstruction process for standard whole-body PET scanners. One unique aspect of total-body imaging is simultaneous coverage of the entire human body, which makes it convenient to perform total-body dynamic PET scans. Therefore, four-dimensional dynamic PET reconstruction and parametric imaging are of great interest in total-body imaging. This article covers some basics of PET image reconstruction and then focuses on three- and four-dimensional PET reconstruction for total-body imaging. Methods for image formation from raw measurements in total-body PET are described. Challenges and opportunities in total-body PET image reconstruction are discussed.


Fluorescence spectroscopy as a tool to detect and evaluate glucocorticoid-induced skin atrophy.
Topical glucocorticoid (GC) therapy has been successfully used in the treatment of several common cutaneous diseases in clinical practice for a long time, and skin atrophy is one of the most typical cutaneous side effects of this therapy. The aim of this study was to evaluate the potential of noninvasive fluorescence spectroscopy (FS) technique in the detection and classification of GC-induced skin atrophy. A total of 20 male Wistar rats were used in the experimental protocol under controlled environmental conditions and with free access to food. One group received topical application of clobetasol propionate 0.05% for 14 days to induce cutaneous atrophy (atrophic group) and the other (control) group received only vehicle application following the same protocol and schedule. Histological analyses and FS measurements with laser excitation at both 532 nm and 408 nm were obtained on days 1 and 15. The FS results were classified as "normal" or "atrophic" according by histological analysis. Fluorescence spectra obtained with excitation at 408 nm allowed a clear distinction between the control and atrophic groups, and were more informative than the those obtained at 532 nm. Our results reveal that, if correctly applied, FS allows noninvasive evaluation of corticosteroid-induced skin atrophy, and thus represents an important step towards better monitoring of undesirable side effects of cutaneous therapy.


The impact of body mass index on perioperative outcomes of open and endovascular abdominal aortic aneurysm repair from the National Surgical Quality Improvement Program, 2005-2007.
Obesity and morbid obesity have been shown to increase wound infections and occasionally mortality after many surgical procedures. Little is known about the relative impact of body mass index (BMI) on these outcomes after open (OAR) and endovascular abdominal aortic aneurysm repair (EVAR). The 2005-2007 National Surgical Quality Improvement Program (NSQIP), a multi-institutional risk-adjusted database, was retrospectively queried to compare perioperative mortality (in-hospital or 30-day) and postoperative wound infections after OAR and EVAR. Patient demographics, comorbidities, and operative details were analyzed. Obesity was defined as a BMI >30 kg/m(2) and morbid obesity as a BMI >40 kg/m(2). Outcomes were compared with t test, Wilcoxon rank sum, χ(2), and multivariate logistic regression. There were 2097 OARs and 3358 EVARs. Compared with EVAR, OAR patients were younger, more likely to be women (26% vs 17%, P < .001), and less obese (27% vs 32%, P < .001). Mortality was 3.7% after OAR vs 1.2% after EVAR (risk ratio, 3.1; P < .001), and overall morbidity was 28% vs 12%, respectively (relative risk, 2.3; P < .001). Morbidly obese patients had a higher mortality for both OAR (7.3%) and EVAR (2.4%) than obese patients (3.9% OAR; 1.5% EVAR) or nonobese patients (3.7% OAR; 1.1% EVAR). Obese patients had a higher rate of wound infection vs nonobese after OAR (6.3% vs 2.4%, P < .001) and EVAR (3.3% vs 1.5%, P < .001). Morbid obesity predicted death after OAR but not after EVAR, and obesity was an independent predictor of wound infection after OAR and EVAR. Morbid obesity confers a worse outcome for death after abdominal aortic aneurysm repair. Obesity is also a risk factor for infectious complications after OAR and EVAR. Obese patients and, particularly, morbidly obese patients should be treated with EVAR when anatomically feasible.


Biochar production with amelioration of microwave-assisted pyrolysis: Current scenario, drawbacks and perspectives.
In recent years, biomass has been reported to obtain a wide range of value-added products. Biochar can be obtained by heating biomass, which aids in carbon sinks, soil amendments, resource recovery, and water retention. Microwave technology stands out among various biomass heating technologies not only for its effectiveness in biomass pyrolysis for the production of biochar and biofuel but also for its speed, volumetrics, selectivity, and efficiency. The features of microwave-assisted biomass pyrolysis and biochar are briefly reviewed in this paper. An informative comparison has been drawn between microwave-assisted pyrolysis and conventional pyrolysis. It focuses mainly on technological and economic scenario of biochar production and environmental impacts of using biochar. This source of knowledge would aid in the exploration of new possibilities and scope for employing microwave-assisted pyrolysis technology to produce biochar.


Automatic detection of bronchial dilatation in HRCT lung images.
Bronchiectasis is an airway disease caused by the dilatation of the bronchial tree, and a bronchovascular pair is formed between a bronchus and a vessel. An abnormal bronchovascular pair is one that has a larger bronchus compared to its accompanying vessel. Typically, bronchi and vessels running perpendicular to the plane of section appear as near-circular rings on computed tomography (CT) scans. This paper describes BV_pairs, a system capable of detecting abnormal bronchovascular pairs in high-resolution CT scans of sparse datasets using a three-stage process: (1) detection of potential bronchovascular pairs, (2) detection of discrete pairs, where there exists no ambiguity as to the artery that accompanies a bronchus, and (3) identification of abnormal pairs with severity levels. The system was evaluated at every stage. The automated scoring for the presence and severity of bronchial abnormalities was demonstrated to be comparable to that of an experienced radiologist (i.e., kappa statistics kappa > 0.5). In addition, BV_pairs was also evaluated on images containing honeycombing regions, since honeycombing cysts appear very similar to bronchi, and the system could successfully differentiate honeycombing cysts from bronchi.


Evaluating the potential of IL-27 as a novel therapeutic agent in HIV-1 infection.
Interleukin 27 (IL-27) is an immunomodulatory cytokine with important roles in both the innate and adaptive immune systems. In the last five years, the addition of exogenous IL-27 to primary cell cultures has been demonstrated to decrease HIV-1 replication in a number of cell types including peripheral blood mononuclear cells (PBMCs), CD4+ T cells, macrophages and dendritic cells. These in vitro findings suggest that IL-27 may have therapeutic value in the setting of HIV-1 infection. In this review, we describe the current knowledge of the biology of IL-27, its effects primarily on HIV-1 replication but also in other viral infections and explore its potential role as a therapeutic cytokine for the treatment of patients with HIV-1 infection.


PGE2 and dibutyryl-cAMP enhance the response of rat granulosa cells to FSH.
Granulosa cells isolated from immature Sprague-Dawley rat ovaries produce progesterone (31.7 pg/micrograms cell protein) in response to an acute FSH stimulus (5 micrograms/ml NIH-FSH-S11, 2 H). After culture for 48 h in the absence of hormones (control culture), progesterone production by the granulosa cells in response to FSH is significantly reduced (2.9 pg/micrograms cell protein). Cells cultured with prostaglandin E2 (PGE2, 1 microgram/ml) or dibutyryl-cAMP (dbcAMP, 1 mM) exhibited a discernibly greater steroidogenic response to FSH (12.5 and 53.4 pg/microgram cell protein, respectively) than that of control cultures. Therefore the presence of PGE2 or dbcAMP in the culture medium helps to maintain the steroidogenic capacity of granulosa cells in culture. It is probable that this capacity is maintained at a locus distal to the production of cAMP by FSH. Paradoxically, granulosa cells cultured with PGE2 produce less cAMP in response to FSH stimulation than cells in control cultures (15.9 vs. 250.3 fm/micrograms cell protein). This may be due to a suppressive effect of prior exposure to PGE2 on the subsequent activity of adenylate cyclase when the FSH is introduced and a concomitant elevation of phosphodiesterase activity.


First evidence of multiple paternity in the blue shark (Prionace glauca).
Multiple paternity (MP) is defined as the behaviour in which females successfully mate with multiple males leading to offspring from different sires within the same litter. MP seems to be frequent and an evolutionary advantage in elasmobranchs. Here the authors report for the first time the occurrence of MP in the cosmopolitan blue shark Prionace glauca L. The evidence, gathered via microsatellite genotyping of pregnant females and their embryos, suggests that MP is very frequent in this species. Knowledge of MP in P. glauca should help describe more precisely its reproductive biology and contribute to the management of its populations.


Purification and culture of adult rat dorsal root ganglia neurons.
To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS)


Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution.
Ab initio quantum mechanical calculations have been used to obtain details of the electron density distribution in a high-resolution refined protein structure. It is shown that with accurate atomic co-ordinates, electron density may be calculated with a quality similar to that which can be obtained directly from crystallographic studies of small organic molecules, and that this density contains information relevant to the understanding of catalysis. Atomic co-ordinates from the 1.8 A and 1.5 A resolution refinements of the crystal structure of protease A from Streptomyces griseus have been used to examine the influence of the environment on the electron density in the side-chain of the active site histidine (His57). The neighbouring aspartic acid 102 is the dominant factor in the environment, and quantum mechanical calculations have been performed on these two residues. Most interesting from the point of view of understanding the catalytic process is the effect that Asp102 has on the electron density in the region of the imidazole nitrogen (N epsilon 2) adjacent to the active site serine 195. In the positively charged imidazolium species, there is a polarization of the N epsilon 2-H bond, reducing the bonding density in a manner that may lower the height of the energy barrier for proton transfer. In the uncharged imidazole species, the proximity of Asp102 causes a movement of density from the lone pair region of the N epsilon 2 into the pi bonding region above and below the plane of the ring. Although it is shown that the primary effect of the aspartic acid is electrostatic, this movement is perpendicular to the direction of the electric field inducing it.


Atypical, multilevel and noncontiguous tuberculous spondylitis that affected the vertebrae of thoracic, lumbar and sacrum: a case report.
Tuberculous spondylitis (TS, also called Spinal tuberculosis, Pott's spine or Pott's disease) is a common extrapulmonary manifestation of tuberculosis (TB), but multilevel, noncontiguous TS cases are rare. Physical examination, CT, MRI imaging, percutaneous biopsy and other lab tests were used to confirm the diagnosis. we report a rare case of atypical, multilevel and noncontiguous TS in a 50-year-old woman. We found four noncontiguous osteolytic lesions in her spine that affected the Intervertebral joints of T10/11, L1/2, L3/4 and L5/S1. Patient was then treated conservatively with anti-TB drugs and was followed-up for about 1 year. The treatment turned out to be successful. The conservative anti-TB treatment was enough at least for this particular patient.


Branched synthetic peptide constructs mimic cellular binding and efflux of apolipoprotein AI in reconstituted high density lipoproteins.
This study investigates the suitability of the trimeric apolipoprotein (apo)AI(145-183) peptide that we recently described, to serve as a model to probe the relationship between apoAI structure and function. Three copies of the apoAI(145-183) unit, composed each of two amphipathic alpha-helical segments, were branched onto a covalent core matrix and the construct was recombined with phospholipids. A similar construct was made with the apoAI(102-140) peptide and used as a comparison with dimyristoylglycerophosphocholine (DMPC)-apoAI complexes. The DMPC-trimeric-apoAI(145-183) complexes had similar immunological reactivity with monoclonal antibodies directed against the 149-186 apoAI sequence (A44), suggesting that the A44 epitope is exposed similarly in both the synthetic peptide and the native apoAI complexes. The complexes generated with the trimeric-apoAI(145-183) bind specifically to HeLa cells with comparable affinity to the DMPC apoAI complexes; they are a good competitor for binding of apoAI to both HeLa cells and Fu5AH rat hepatoma cells; finally, these complexes promote cholesterol efflux from Fu5AH cells with an efficiency comparable with the apo AI/lipid complexes. To study LCAT activation by the trimeric apo AI(145-183) construct, complexes were prepared with dipalmitoylphosphatidylcholine (DPPC), cholesterol (C) and either the trimeric construct or apoAI. LCAT activation by the trimeric construct was much lower than by apo AI, possibly because the conformation of the trimeric 145-183 peptide in DPPC/C/peptide complexes does not mimic that of apoAI in the corresponding complexes. In comparison, the complexes generated with the multimeric apoAI(102-140) construct had a poor capacity to mimic the physico-chemical and biological properties of apoAI. The apoAI(102-140) construct had low affinity for lipid compared with the (145-183) construct. After association with lipids, it was a poor competitor of DMPC-apoAI complexes for cellular binding and had only limited capacity to promote cholesterol efflux. These results suggest trimeric constructs can serve as an appropriate models for apoAI, enabling further investigations and new experimental approaches to determine the structure-function relationship of apoAI.


The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.
Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown. Both N-oxide metabolites reverted to parent compound under standard drying (2hr) and extraction conditions. Card type significantly affected the outcome, with 14% and 22% degradation occurring for clozapine-N-oxide and amitriptyline-N-oxide on a brand of untreated DBS cards, compared to 59 and 88% on a brand of treated DBS cards. Enrichment of the parent compound ex vivo leads to overestimation of circulating blood concentration and inaccurate determination of the PK profile.


Modelling the economic and health consequences of cardiac resynchronization therapy in the UK.
Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in advanced heart failure, but its cost-effectiveness is still unclear. This analysis assessed the economic and health consequences in the UK of implanting a CRT in patients with NYHA class III-IV heart failure. A discrete event simulation of heart failure was used to compare the course over 5 years of 1000 identical pairs of patients -- one receiving both CRT and optimum pharmacologic treatment (OPT), the other OPT alone. All inputs were obtained from the data collected in the CArdiac REsynchronization in Heart Failure (CARE-HF) trial and a hospital in the UK. Direct medical costs (in 2004 pound) from the perspective of the National Health Service were considered. Both costs and benefits were discounted at 3.5%. Sensitivity analyses addressed all model inputs and multivariate analyses were performed by varying key parameters simultaneously. The model predicted 471 deaths and 2263 hospitalizations over 5 years with OPT alone and 348 deaths and 1764 hospitalizations with CRT, equivalent to a 26% reduction in mortality and 22% in hospitalizations, at a discounted cost of pound 11,423 per patient with CRT vs. pound 4,900 with OPT alone. CRT was predicted to increase quality-adjusted survival by 0.43 QALYs per patient, resulting in an incremental cost-effectiveness ratio of pound 15,247 per QALY gained (range: pound 12,531- pound 23,184). Sensitivity analyses revealed that this outcome was most sensitive to time horizon and cost of implantation. Based on these 5-year analyses, CRT is expected to yield substantial health benefits at a reasonable cost.


Sulfonated polyHIPE/nanoclay composites with hierarchically porous structure for efficient removal of endocrine-disrupting hormone from aqueous solution.
The objective of this study is the synthesis of macroporous polystyrene-based polyHIPE/nanoclay (p[HIPE]/NClay) monoliths and post-functionalization of the monoliths through sulfonation to improve the structural and textural properties as well as adsorption performances toward bisphenol A (BPA) as an endocrine-disrupting chemical. The adsorption tests were conducted with raw p(HIPE), nanoclay, p(HIPE)/NClay, and sulfonated samples in order to obtain insights in the adsorption mechanism. The synergy between clay embedding and sulfonation resulted in higher BPA removal performance of p(HIPE)/NClay@S sample (96% removal) when compared with the raw polyHIPE (52% removal). The adsorption efficiency was mainly attributed to the functionality, followed by porosity and hydrophilicity of the as-synthesized materials. Considering the roles of hydrophobic, hydrogen-bonding, and π-π stacking interactions, the adsorption mechanism was discussed by using X-ray photoelectron spectroscopy (XPS) analysis. Moreover, the experimental parameters including solution pH, co-existing anions, ionic strength, and temperature were investigated in detail. The adsorption data were fitted to isotherm and kinetic models. The composite adsorbents also displayed excellent regeneration and stability until the fifth cycle. This research provides fresh insights into the effective adsorptive removal of endocrine-disrupting hormones by sulfonated porous nanoclay-polymer monoliths. PRACTITIONER POINTS: Sulfonated p (HIPE)/nanoclay monoliths were prepared. Bisphenol A adsorption mechanism was explored in detail. Nanoclay incorporation and sulfonation greatly enhanced the removal efficiency. The composite could be used until the fifth cycle.


[Malleolar osteotomy--osteotomy as approach].
Both arthroscopic and open surgical techniques may be used for treatment of osteochondral lesions of the ankle joint. Osteotomy around the ankle joint is a well established technique to extend the approach in cases where the osteochondral lesions are located more posteriorly. Medial, oblique, monoplanar malleolar osteotomy should be used in patients with lesions of the medial talus shoulder. The posterolateral ostechondral lesions are less frequent and in such cases distal fibular osteotomy is recommended. In this study the indications for different forms of osteotomy are discussed and the surgical techniques are described.


Detection of cutaneous Leishmania infection in paraffin-embedded skin biopsies using the polymerase chain reaction.
In this study the polymerase chain reaction (PCR) with previously developed oligonucleotide primers was used to detect Leishmania aethiopica in paraffin-embedded skin biopsy specimens. The Leishmania-specific 120 base pair fragment of the kinetoplast deoxyribonucleic acid (kDNA) minicircles has been amplified from all parasitologically or histologically confirmed cases of cutaneous leishmaniasis (CL), as demonstrated by gel electrophoresis and hybridization with L. aethiopica kDNA. Control specimens from patients with skin diseases other than CL were all negative. Using PCR, Leishmania were demonstrated in the skin lesions of 7 cases in a group of 40 patients in whom the parasites could not be demonstrated by histopathology or culture in vitro although lesions were clinically suggestive of CL. These data indicate that PCR, carried out on DNA extracted from formalin-fixed and paraffin-embedded tissue specimens, is a valuable method for the diagnosis of CL, especially in chronic cases where the parasite load in the lesion is low.


Effect of ERCC8 tagSNPs and their association with H. pylori infection, smoking, and alcohol consumption on gastric cancer and atrophic gastritis risk.
Excision repair cross-complementing group 8 (ERCC8) plays a critical role in DNA repair. Genetic polymorphisms in ERCC8 may contribute to the risk of cancer development. We selected tag single nucleotide polymorphisms (tagSNPs) in Chinese patients from the HapMap database to investigate associations with gastric cancer and its precursors. Genomic DNA was extracted from 394 controls, 394 atrophic gastritis, and 394 gastric cancer cases in northern Chinese patients, and genotypes were identified using the Sequenom MassARRAY system. We found that the ERCC8 rs158572 GG+GA genotype showed a 1.651-fold (95 % confidence interval (CI) = 1.109-2.457, P = 0.013) increased risk of gastric cancer compared with the AA genotype, especially in diffuse type. Stratified analysis comparing the common genotype revealed significantly increased gastric cancer risk in males and individuals older than 50 years with rs158572 GA/GG/GG+GA genotypes, while individuals older than 50 years with rs158916 CT/CC+CT genotypes were less susceptible to atrophic gastritis. Haplotype analysis showed that the G-T haplotype was associated with increased risk of gastric cancer. Statistically significant interactions between the two ERCC8 tagSNPs and Helicobacter pylori infection were observed for gastric cancer and atrophic gastritis risk (P < 0.05). Smokers and drinkers with ERCC8 rs158572 GG+GA genotype were more susceptible to gastric cancer compared with non-smokers and non-drinkers homozygous for AA. Our findings suggested that ERCC8 rs158572 and rs158916, alone or together with environmental factors, might be associated with gastric cancer and atrophic gastritis susceptibility. Further validation of our results in larger populations along with additional studies evaluating the underlying molecular function is required.


Light-increased cGMP and K+ conductance in the hyperpolarizing receptor potential of Onchidium extra-ocular photoreceptors.
The phototransduction mechanism of the extra-ocular photoreceptor cells Ip-2 and Ip-1 in the mollusc Onchidium ganglion was examined. Previous work showed that the depolarizing receptor potential of another extra-ocular photoreceptor cell, A-P-1 is produced by a decrease of the light-sensitive K+ conductance activated by a second messenger, cGMP and is inactivated by the hydrolysis of cGMP. Here, a hyperpolarizing receptor potential of Ip-2 or Ip-1 was associated with an increase in membrane conductance. When Ip-2 or Ip-1 was voltage-clamped near the resting membrane potential, light induced an outward photocurrent corresponding to the above hyperpolarization. The spectral sensitivity had a peak at 510 nm. The shift of reversal potentials of the photocurrent depended on the Nernst equation of K(+)-selective conductance. The photocurrent was blocked by 4-AP and L-DIL, which are effective blockers of the A-P-1 light-sensitive K+ conductance. These results suggested that the hyperpolarization is mediated by increasing a similar light-sensitive K+ conductance to that of A-P-1. The injection of cGMP or Ca2+ into a cell produced a K+ current that mimicked the photocurrent. 4-AP and L-DIL both abolished the cGMP-activated K+ current, while TEA suppressed only the Ca(2+)-activated K+ current. These results indicated that cGMP is also a second messenger that regulates the light-sensitive K+ conductance. The photocurrent was blocked by LY-83583, a guanylate cyclase (GC) inhibitor, but was unaltered by zaprinast, a phosphodiesterase (PDE) inhibitor. Together, the present results suggest that increasing the internal cGMP in Ip-2 or Ip-1 cells light-activates GC rather than inhibits PDE, thereby leading to an increase of the light-sensitive K+ conductance and the hyperpolarization.


Morphologic survey of the condylomatous lesions in dysplastic and neoplastic epithelium of the uterine cervix.
One hundred eighty-four women with a histologically verified dysplastic or neoplastic lesion in the uterine cervical epithelium were histologically assessed with special reference to the presence of the various histological types of condyloma in these epithelial specimens. Histological changes fulfilling the previously outlined criteria of the flat, inverted, and papillomatous condylomas were encountered in 91 (49.4%) women. Condylomatous lesions were seen in association with all degrees of epithelial atypia from mild dysplasia to frankly invasive cervical carcinoma, which seemed to develop at significantly earlier age when concomitant condylomatous lesion was present than with its absence (p less than 0.001). The serious consideration of the relationship between the condylomatous lesions and the uterine cervical was emphasized.


Development of an electrochemical impedance spectroscopy based biosensor for detection of ubiquitin C-Terminal hydrolase L1.
Year over year, the incidence of traumatic brain injury (TBI) in the population is dramatically increasing; thus, timely diagnosis is crucial for improving patient outcomes in the clinic. Ubiquitin C-terminal hydrolase L1 (UCH-L1), a blood-based biomarker, has been approved by the FDA as a promising quantitative indicator of mild TBI that arises in blood serum shortly after injury. Current gold standard techniques for its quantitation are time-consuming and require specific laboratory equipment. Hence, development of a hand-held device is an attractive alternative. In this study, we report a novel system for rapid, one-step electrochemical UCH-L1 detection. Electrodes were functionalized with anti-UCH-L1 antibody, which was used as a molecular recognition element for selective sensing of UCH-L1. Electrochemical impedance spectroscopy (EIS) was used as a transduction method to quantify its binding. When the electrode was incubated with different concentrations of UCH-L1, impedance signal increased against a concentration gradient with high logarithmic correlation. Upon single-frequency analysis, a second calibration curve with greater signal to noise was obtained, which was used to distinguish physiologically relevant concentrations of UCH-L1. Notably, our system could detect UCH-L1 within 5 min, without a washing step nor bound/free separation, and had resolution across concentrations ranging from 1 pM to 1000 pM within an artificial serum sample. These attributes, together with the miniaturization potential afforded by an impedimetric sensing platform, make this platform an attractive candidate for scale-up as a device for rapid, on-site detection of TBI. These findings may aid in the future development of sensing systems for quantitative TBI detection.


[Clinical results of the treatment of bacterial infections in children with ceftazidime].
Ceftazidime (Fortum-Glaxo) was administrated to 19 children with urinary tract infections and to 21 children with pneumonia. Clinical symptoms of the infections resolved in 17 children (89%) with the urinary tract infections treated with ceftazidime within 4 days. The remaining children (11%) recovered after 7 days of therapy. Clinical symptoms of pneumonia resolved in 19 children (90%) within 7 days of the treatment. A significant improvement was achieved in the remaining 2 children after 10 days of the treatment.


On-line preconcentration and separation of Co, Ni and Cd via capillary microextraction on ordered mesoporous alumina coating and determination by inductively plasma mass spectrometry (ICP-MS).
In this paper, an ordered mesoporous alumina coating was prepared and applied to capillary microextraction (CME) of trace Co, Ni and Cd for the first time. The coated capillary was used for on-line coupling CME with inductively plasma mass spectrometry (ICP-MS) for the determination of trace metals of Co, Ni and Cd. The porous structure of Al2O3 coating was examined by SEM and TEM. The effects of the extraction parameters including pH, sample flow rate and volume, elution solution and interfering ions on the recovery of analytes have been investigated and optimized. Under the optimized conditions, the limits of detection were 0.33, 1.5 and 1.4 ng L(-1) for Co, Ni and Cd, respectively, with a preconcentration factor of 10 times. The precisions for all investigated elements were 2.7, 4.1 and 2.5% (c=0.05 ng L(-1), n=7), for Co, Ni and Cd, respectively, and the sample frequency was 8 h(-1). The proposed method was successfully applied for the analysis of trace metals in water, rice and urine samples with the recovery of 94-105%. In order to validate the proposed method, two certified reference materials of GBW 0913 human urine and NIES No.10-b rice flour were analyzed, and the determination values are in good agreement with the certified values. The ordered mesoporous Al2O3 coated capillary can be used more than 20 times without decreasing the extraction efficiency.


Subcortical control of the default mode network: Role of the basal forebrain and implications for neuropsychiatric disorders.
The precise interplay between large-scale functional neural systems throughout the brain is essential for performance of cognitive processes. In this review we focus on the default mode network (DMN), one such functional network that is active during periods of quiet wakefulness and believed to be involved in introspection and planning. Abnormalities in DMN functional connectivity and activation appear across many neuropsychiatric disorders, including schizophrenia. Recent evidence suggests subcortical regions including the basal forebrain are functionally and structurally important for regulation of DMN activity. Within the basal forebrain, subregions like the ventral pallidum may influence DMN activity and the nucleus basalis of Meynert can inhibit switching between brain networks. Interactions between DMN and other functional networks including the medial frontoparietal network (default), lateral frontoparietal network (control), midcingulo-insular network (salience), and dorsal frontoparietal network (attention) are also discussed in the context of neuropsychiatric disorders. Several subtypes of basal forebrain neurons have been identified including basal forebrain parvalbumin-containing or somatostatin-containing neurons which can regulate cortical gamma band oscillations and DMN-like behaviors, and basal forebrain cholinergic neurons which might gate access to sensory information during reinforcement learning. In this review, we explore this evidence, discuss the clinical implications on neuropsychiatric disorders, and compare neuroanatomy in the human vs rodent DMN. Finally, we address technological advancements which could help provide a more complete understanding of modulation of DMN function and describe newly identified BF therapeutic targets that could potentially help restore DMN-associated functional deficits in patients with a variety of neuropsychiatric disorders.


Phosphorylation by protein kinase C of the muscarinic acetylcholine receptor.
Muscarinic acetylcholine receptors purified from porcine cerebrum were phosphorylated by protein kinase C purified from the same tissue. More than 1 mol of phosphate was incorporated per mole of receptor, with both serine and threonine residues being phosphorylated. Neither the degree nor the rate of the phosphorylation was affected by the presence or absence of acetylcholine. GTP-sensitive high-affinity binding with acetylcholine was observed for muscarinic receptors reconstituted with GTP-binding proteins (Gi or Go), irrespective of whether muscarinic receptors or the GTP-binding proteins had been phosphorylated by protein kinase C or not. This indicates that the interaction between purified muscarinic receptors and purified GTP-binding proteins in vitro is not affected by their phosphorylation.


An anatomic study of trifurcate iliotibial bands for correcting valgus knee deformity.
The iliotibial band (ITB) trifurcates into the anterior, central and posterior branches at the knee level, and sometimes the branches must be selectively released to correct the valgus knee deformity during total knee arthroplasty. However, the anatomical morphology of the trifurcate ITBs has not been investigated. Fifty-two knees from 26 embalmed cadavers were dissected to observe and record the relationship of the three branches given off from the ITB trifurcation. Fourteen parameters with regard to the length, width, thickness, and trifurcate angle of each branch were measured. These parameters were compared between sex and sides (left or right). Meanwhile, the correlations between parameters and subject age, weight and height were assessed. The longest, widest and thickest branches of the ITB were the posterior band (59.82±5.14mm), anterior band (39.56±4.17mm) and central band (2.61±0.36mm), respectively. The length and thickness of ITB were significantly larger in males than in females (P<0.05). No significant differences were found between sides (P>0.05). The ITB thickness showed a negative correlation with subject age, while the length and width of the ITB were positively correlated with subject height and weight, respectively. This study provided an anatomical reference of trifurcate ITBs to help the release of ITB in valgus knees. The anatomical variations regarding the subject's sex, age, height and weight should be considered in the selective release of ITB.


Freedom to enjoy learning in the 21st century: developing an active learning culture in nursing.
In 1994, the Wolfson School of Health Sciences was created in Thames Valley University, UK. This paper discusses an active learning approach being implemented throughout the university, and gives an outline of its application within nursing education. Practising as a confident, competent, reflective practitioner in the profession of nursing cannot automatically commence on the day of registration. Rather, the philosophical underpinnings necessary should be fostered throughout the initial nursing education curricula. In a political climate where there is a strong emphasis on efficiency, nurse teachers need to reconsider how the acquisition of nursing knowledge is facilitated. A description of how an active learning approach is being further developed in the nursing skills laboratory and the physiology laboratory is given. An outline identifies how these facilities may help students of nursing to gain knowledge and skills in relation to respiration. The authors recognize that while laboratories have been used widely in general education, their use has been limited in nursing education, particularly in the UK. Informal feedback from students implies that not only do they enjoy learning in these facilities, but also motivation towards learning is raised, an important element in the learning process. It is suggested that this will result ultimately in increased nursing competence. The authors acknowledge that these are preliminary informal findings and that formal investigation is required.


Teaching clinic lowers radiology utilization. A look at how to achieve more cost-effective imaging.
Discover how an Oregon medical clinic made great strides decreasing radiology utilization after implementing a continuous quality improvement project that was embraced by physicians.


Stent treatment of malignant gastric outlet obstruction: the effect on rate of gastric emptying, symptoms, and survival.
Advanced pancreatic cancer and other malignancies located proximal to the small bowel might cause gastric outlet obstruction (GOO) resulting in nausea, vomiting, dehydration, and malnutrition. Self-expandable metal stents (SEMS) to a large extent have replaced surgical treatment, with gastro-entero-anastomosis as palliative treatment for GOO. The aim of the present study was to evaluate the effect of duodenal stenting on the rate of gastric emptying, symptoms, and survival. Patients with endoscopically verified malignant obstruction of the proximal duodenum were included. Gastric emptying rate was measured prior to and within 1 week after stent placement using a meal containing (13)C-octanoic acid as a marker. Symptoms related to GOO were assessed by the patients before and 2 weeks after stent treatment and during the gastric emptying tests. All patients were followed up until death. In the patients included (n = 17), all studied variables of gastric emptying improved significantly following treatment, and a reduction in self-reported obstructive symptoms was observed. There was no correlation between survival and the rate of gastric emptying before or after, or the change in the rate of emptying. The present study demonstrated that treatment with SEMS results in improved gastric emptying in most patients with GOO and a corresponding reduction in self-reported obstruction symptoms. However, survival and emptying were not related. The present findings provide further evidence that treatment with stents is an effective palliative treatment in patients with GOO.


Detection of DNA Methylation in Genomic DNA by UHPLC-MS/MS.
DNA methylation serves to mark DNA as either a directed epigenetic signaling modification or in response to DNA lesions. Methods for detecting DNA methylation have become increasingly more specific and sensitive over time. Conventional methods for detecting DNA methylation, ranging from paper chromatography to differential restriction enzyme digestion preference to dot blots, have more recently been supplemented by ultrahigh performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) to accurately quantify specific DNA methylation. Methylated DNA can also be sequenced by either methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) or single-molecule real-time sequencing (SMRTseq) for identifying genomic locations of DNA methylation. Here we describe a protocol for the detection and quantification of epigenetic signaling DNA methylation modifications including, N6-methyladenine (6mA), N4-methylcytosine (4mC) and C5-methylcytosine (5mC) in genomic DNA by triple quadrupole liquid chromatography coupled with tandem mass spectrometry (QQQ-LC-MS/MS). The high sensitivity of the UHPLC-MS/MS methodology and the use of calibration standards of pure nucleosides allow for the accurate quantification of DNA methylation.


Evidence for the coupling of T7 DNA injection with its transcription during infection.
The kinetics of T7 phage DNA transfer from the virion into E. coli during infection in the presence of chloramphenicol was compared under the same conditions with the kinetics of its in vivo transcription. The results obtained allow us to conclude that these two processes are tightly coupled.


The potential association between obesity and bipolar disorder: A meta-analysis.
Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. In this study, we conducted a meta-analysis to explore the association between obesity and BD by combining 9 cross-sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I(2) and Q statistic. Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40-2.23; Q=44.62, P<0.001, I(2)=82.1%). Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. Obesity is positively associated with BD.


lncRNA Up-Regulated in Nonmuscle Invasive Bladder Cancer Facilitates Tumor Growth and Acts as a Negative Prognostic Factor of Recurrence.
While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA-UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer. We analyzed the expression of lncRNA-UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction. Data were compared with clinicopathological parameters using the Kaplan-Meier method and multivariate Cox regression analysis. The functions of lncRNA-UNMIBC were assessed by silencing the lncRNA in vitro and in vivo. RNA immunoprecipitation was performed to assay whether lncRNA-UNMIBC could be physically associated with EZH2 (enhancer of zeste homolog 2) and SUZ12 (SUZ12 polycomb repressive complex 2 subunit), which are core components of PRC2 (polycomb repressive complex 2). Chromatin immunoprecipitation was done to examine histone modification status. The expression level of lncRNA-UNMIBC was up-regulated in the tissues of 45 cases of primary nonmuscle invasive bladder cancer compared with normal mucosa. Kaplan-Meier estimates showed that lncRNA-UNMIBC expression was significantly associated with recurrence (log rank test p = 0.0151). We also found that lncRNA-UNMIBC had a key role in G0/G1 arrest. Furthermore, RNA and chromatin immunoprecipitation assays demonstrated that lncRNA-UNMIBC was physically associated with EZH2 and SUZ12, leading to an altered histone H3 lysine 27 methylation status of target genes. These findings indicate that lncRNA-UNMIBC can facilitate tumor growth and may act as a negative prognostic factor of recurrence.


Development of a prophylactic regime using long-acting tetracycline for the control of redwater and heartwater in susceptible cattle moved into an endemic area.
Thirty young crossbred steers were purchased from a tick-borne disease-free farm in South Africa, shown to be serologically negative to Babesia bigemina/bovis and Cowdria ruminantium, and moved to an experimental farm where babesiosis and heartwater were known to be endemic. The animals were allowed to graze as a herd on tick-infested areas of the farm for 90 days from the beginning of April but were separated into three groups of 10 for treatment. One group received a prophylactic regime of two injections of 20 mg/kg of a long-acting oxytetracycline on days 7 and 14 after introduction, one received a regime of three similar injections on days 7, 14 and 21 and the other group remained untreated prophylactically. The animals were observed early each morning in a crush, rectal temperatures being taken daily and blood smears when clinical signs of disease occurred. When clinical disease was confirmed in individual animals appropriate therapeutic treatment was implemented. In addition tick counts were made weekly. All untreated control animals required treatment for redwater between days 23 and 32 and eight of them then contracted heartwater of which five died despite therapy. Four animals from the group receiving two injections of oxytetracycline and one receiving three injections also contracted redwater but rather later. During the initial 35 day assessment period it was noticed that the majority of Boophilus ticks failed to engorge on the oxytetracycline-treated animals. In the second phase of the trial theileriosis (T. mutans-type) became evident in many animals and appeared to precipitate new or recrudescent clinical redwater and heartwater in several of them.(ABSTRACT TRUNCATED AT 250 WORDS)


Internalized Homonegativity and the Challenges of Having Same-Sex Desires in the Lebanese Context: A Study Examining Risk and Protective Factors.
Internalized homonegativity (IH) has received increased attention in the literature on sexual minorities. Nevertheless, there is a lack of research on IH in conservative Arab cultures like Lebanon. The present study aimed to cover this gap by exploring risk and protective factors of IH in Lebanese sexual minorities. A hierarchical multiple regression (N = 210) revealed that religiosity, parental rejection (actual or anticipated), and legal discrimination were significant risk factors of IH, while sense of belonging to the LGBT community was a strong protective factor. Although self-compassion did not emerge as a predictor, it had interesting interactions on the bivariate level. Results, limitations, clinical implications, and recommendations for future research and policy making are discussed.


Role of bedside ultrasound in CMV retinitis: a case report.
We present a case of retinal detachment diagnosed by emergency department bedside ultrasonography in a patient with CMV retinitis. The indications and findings of ocular ultrasonography are discussed.


CT and 99mTc-WBC vs colonoscopy in the evaluation of inflammation and complications of inflammatory bowel diseases.
The goal of this study was to evaluate the accuracy of computerized tomography (CT) and 99mTc-white blood cell (WBC) scintigraphy versus colonoscopy in assessing inflammatory bowel diseases (IBD) in a large population of children. In a patient population of 313 consecutive children who had a 99mTc-WBC scan, 106 colonoscopies were done within a median time interval of 8 days of the 99mTc-WBC scan. One hundred and three CT scans were performed on 84 patients. Of the 42 CT scans obtained within a short time interval after the 99mTc-WBC scan, 21 (50%) were normal. In the 21 children with a positive 99mTc-WBC scan, 62% (13/21) of the CT scans underestimated the bowel wall inflammation in at least one segment. In the children with a negative 99mTc-WBC study, there were 17 negative CT examinations and 4 examinations showing an abnormal terminal ileum. When CT was compared with colonoscopy in assessing inflammation, there were five true-negative CT, two true-positive CT, no false-positive, and seven false-negative CT examinations. When 99mTc-WBC scintigraphy was compared with colonoscopy in assessing inflammation, there were seven true-positive, two false-negative, five true-negative, and no false-positive 99mTc-WBC studies. The 99mTc-WBC scan was positive in five patients with a false-negative CT examination. Of the total 103 CT scans obtained, 53 (51%) were normal. Four abscesses (3.8%) were demonstrated by CT. 99mTc-WBC scintigraphy is more sensitive than CT for detecting inflammation of the bowel wall. The incidence of complications from IBD in this retrospective study was much lower than had been previously reported.


Folding propensity and biological activity of peptides: the effect of a single stereochemical isomerization on the conformational properties of bombinins in aqueous solution.
Folding propensities of bombinins H2 and H4, two members of amphibian bombinins H, a family of 17-20 residue alpha-helical peptides, have been investigated by means of circular dichroism (CD) measurements and molecular dynamics (MD) simulations. The two peptides, with primary structure IIGPVLGLVGSALGGLLKKI-NH2 and differing only for the configuration of the second aminoacid (an L-isoleucine in H2 and a D-alloisoleucine in H4) behave rather differently in solution. In particular both CD measurements and MD simulations indicate that bombinin H2 shows a markedly higher tendency to fold. From a careful inspection of MD trajectories it emerges that the stereochemical isomerization mutation of residue 2 to D-alloisoleucine in H4 peptide, drastically decreases its ability to form intrapeptide contacts. MD simulations also indicate that the conformational sampling in both systems derives from a subtle combination of energetic and entropic effects both involving the peptide itself and the solvent. The present results have been finally paralleled with preliminary information on bombinins H2 and H4 biological activity, i.e. interaction with membrane, supporting the hypothesis of an "already folded" conformation in water rather than interfacial folding tenet.


Primary iliac bone lymphoma with multiple bone involvement evaluated by 18 fluorodeoxyglucose positron emission tomography: A case report.
Involvement of bone by lymphoma usually occurs in the setting of widespread systemic disease. The primary bone lymphoma (PBL) is a rare entity, accounting for 3 to 7% of primary malignant bone tumors and less than 2% of all lymphomas. The Multifocal forms are even rarer and can be confused with bone metastases. The diagnosis is guided by the clinic and radiology, but only the histology confirms accurate diagnosis. We report a rare case of primitive iliac lymphoma in a 58-year-old man. The pathological study was in favor of a diffuse large B-cell lymphoma. An 18 fluorodesoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) performed as part of the staging assessment revealed multifocal bone involvement. This case highlights the importance to evoke the diagnosis of primary bone lymphoma, even if it presents in an unusual site, as well as the value of metabolic imaging in assessing the extent of the disease.


Attenuation of neostriatal preproenkephalin and preprotachykinin mRNA abundance by chronic treatment with the kainate/quisqualate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione in the rat brain.
The present investigation assessed the effect of chronic blockade of kainate/quisqualate binding sites with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the neostriatum of the rat brain. Daily injection of CNQX for seven consecutive days decreased PPE mRNA abundance approximately 25% below vehicle-injected controls in dorsolateral, dorsomedial, anterior caudate-putamen (dlCPu, dmCPu and aCPu, respectively) and nucleus accumbens (NAc). Similarly, PPT mRNA abundance was significantly decreased in dlCPu, dmCPu and aCPu but not in the accumbens. The data demonstrate that non-NMDA receptor activity modulates basal levels of expression of PPE and PPT mRNAs in the neostriatum of the rat brain.


Which cava anastomotic techniques are optimal regarding immediate and short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations.
It has long been debated whether cava anastomosis should be performed with the piggyback technique or cava replacement, with or without veno-venous bypass (VVB), with or without temporary portocaval shunt (PCS) in the setting of liver transplantation. To identify whether different cava anastomotic techniques and other maneuvers benefit the recipient regarding short-term outcomes and to provide international expert panel recommendations. Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021240979). Of 3205 records screened, 307 publications underwent full-text assessment for eligibility and 47 were included in qualitative synthesis. Four studies were randomized control trials. Eighteen studies were comparative. The remaining 25 were single-center retrospective noncomparative studies. Based on existing data and expert opinion, the panel cannot recommend one cava reconstruction technique over another, rather the surgical approach should be based on surgeon preference and center dependent, with special consideration toward patient circumstances (Quality of evidence: Low | Grade of Recommendation: Strong). The panel recommends against routine use of vevo-venous bypass (Quality of evidence: Very Low | Grade of Recommendation: Strong) and against the routine use of temporary porto-caval shunt (Quality of evidence: Very Low | Grade of Recommendation: Strong).


Formation and characterization of protein-based films from yellow pea (Pisum sativum) protein isolate and concentrate for edible applications.
This study investigated the properties of films or bioplastics fabricated using a wet processing method from yellow pea protein isolate (YPI) and protein concentrate (YPC) for potential application in food packaging. The wet processing method included mixing the protein with water and glycerol followed by casting and drying the films in a humidity- and temperature-controlled chamber. Whey protein isolate (WPI) and a film from a blend of equal amounts of YPI and WPI, labelled as YPI + WPI, were also studied. Fourier transform-infra red analysis revealed that films from YPI, YPC, WPI and YPI + WPI were formed by protein polymerisation with the plasticiser, glycerol, via hydrophobic and hydrophilic interactions. The protein films had contact angles of <90° demonstrating that they had a hydrophilic surface, with YPC < YPI < YPI + WPI < WPI. The pattern of ultraviolent light transmission of the films was WPI > YPC > YPI + WPI > YPI, whereas the mechanical and thermal resilience of films formulated from YPI, YPC and the protein blend were comparable to the properties of WPI-based films. The findings demonstrate that yellow pea proteins can be used as biomaterials to develop protein and protein-blend films or bioplastics for food packaging and edible applications.


Pediatric Resident Preparedness and Educational Experiences With Informed Consent.
Informed consent is an essential component of optimal patient care. Scant data exist about pediatric residents' experiences, comfort level, and educational exposure to informed consent discussions. Electronic survey of a random selection of members of the American Academy of Pediatrics Section for Medical Students, Residents, and Fellows regarding consent practices and processes for 5 commonly encountered pediatric procedures/situations: lumbar puncture, neonatal central line, pediatric sedation, intubation, and administration of blood products. Overall response rate was 34.7% (1071 participants of 3084 invited). Responses from 622 active categorical pediatric residents were analyzed. Almost all respondents (99%) endorsed the importance of informed consent for best patient care. Observation was the most frequently reported educational modality. Over 90% had obtained consent for lumbar puncture and blood products but only 27.6% for intubation. Between 9% and 31% of respondents reported obtaining consent for specific procedures in which they were not expected to actively participate. Depending on the procedure, a variable number of respondents reported not feeling prepared to discuss the benefits (1-23%) or risks (2-31%) of these procedures with patients and/or parents. Respondents felt significantly less prepared to discuss risks (P < .05 for each procedure). A significant percentage of respondents reported not feeling comfortable with discussing key components of informed consent. A minority of respondents reported being engaged in obtaining consent for procedures in which they are not expected to actively participate. Best practices for resident involvement in informed consent discussions need to be defined and incorporated into resident education.


Heterogeneity of macrophages in response to lymphokines and other signals.
Macrophages which are intimately involved in acute and chronic inflammatory reactions are functionally heterogeneous not only with regard to the expression of constitutive functions but also in their response to lymphokine signals. The biological basis of this heterogeneity is poorly understood. Whether we are dealing with true subpopulations or with intermediately stable phenotypes has not been resolved. To study these questions we adopted a bone marrow liquid culture system in which bone marrow cells--in the presence of a colony-stimulating factor--proliferate and differentiate into macrophages. This culture system was taken here as a model to study the expression of various functions by macrophages in the course of maturation. Several tests were performed daily and in parallel from the same batch of cells. It was found that certain functions were expressed early and were also characteristic for mature macrophages such as Fc receptors, phagocytosis of latex beads and unspecific esterase. Other functions appeared and disappeared in an ordered sequence, such as the response to macrophage migration inhibitory factor and chemotactic factor as well as the production of interferon and plasminogen activator. The time course of functional expression was strongly dependent on proliferation of precursor cells as well as on proliferation of differentiated macrophages. It is concluded that the transient phenotypic expression of functions during differentiation is the basis for the functional heterogeneity of macrophages.


Environmental Enrichment Accelerates the Ontogeny of Cryptic Behavior in Pharaoh Cuttlefish (Sepia pharaonis).
We examined effect of environmental enrichment on cuttlefish, the most neutrally advanced invertebrate, to compare species variation of genetic and environmental influences. Cuttlefish were reared from seven to 117 days in one of three environments, namely, "poor" (artificial bottom without objects), "standard" (sandy bottom), and "enriched" (sandy bottom with objects). In Experiment 1, we explored whether enrichment affects the exhibition of crypsis in the cuttlefish. The cuttlefish in the standard and enriched environments spent most of their time at the bottom, exhibiting the mottled or disruptive pattern starting at 27 days of age. On the contrary, those in the poor environment exhibited uniform pattern starting at 87 days of age. Additionally, they repeatedly attempted to dig from 27 to 87 days of age, and moved around by hovering from 77 to 117 days of age. In Experiment 2, we exposed the cuttlefish to six novel substrates every other month after 53 days of age to verify whether enrichment actually affected the maturation of cryptic ability. Cuttlefish from the poor environment tended not to dig into white sandy bottom at 53-55 days of age. Additionally, they did not clearly exhibit appropriate body patterns in response to the six substrates compared to those from the other two environments at 81-83 days of age. However, at 113-115 days of age, most cuttlefish from the three environments exhibited similar cryptic behaviors in response to novel substrates. We conclude that physical enrichment promotes crypsis and accelerates the maturation of this ability in cuttlefish.


An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors.
Here we report a female patient with elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). At age 71, she developed gait disturbance, followed by memory disturbance 1 year later. She had been treated for hypertension and diabetes mellitus for 19 years. There apparently was low penetrance of disease. Magnetic resonance imaging (MRI) findings showed typical features of CADASIL, and the R607C mutation was detected in exon 11 in NOTCH3. This case strongly indicates that CADASIL should be considered when typical findings are observed on MRI even in cases of elderly onset with multiple cerebrovascular risk factors.