Calvarial Reconstruction.
Calvarial reconstruction is a challenge to reconstructive surgeons, especially considering protection of intracranial contents. In recent years, the advent of multiple reconstructive materials adds tools to the surgical armamentarium. Options include autologous split calvarial and rib grafts and alloplastic materials such as titanium mesh, methyl methacrylate, calcium hydroxyapatite, and polyetheretherketone. The most important aspect of cranial reconstruction still lies in finding the most aesthetic, safe, and reliable means of filling a defect.


Does Twice-weekly Cabergoline Improve Anthropometrical and Biochemical Profiles in Prediabetes? A Randomized Double-blind Clinical Trial Pilot Study.
Dopaminergic signaling is one of the regulatory pathways being investigated for its implication in glucose metabolism. The aim of this study was to determine the effect of cabergoline on biochemical and anthropometric parameters in prediabetes stage (impaired fasting glucose and impaired glucose tolerance). In this double blind, placebo-controlled, pilot study, 27 prediabetic adults were randomized to receive 0.25-mg cabergoline twice weekly for two weeks, followed by 0.5 mg twice weekly for next 14 weeks (n = 13) or placebo (n = 14). All subjects were advised to follow a 500 kcal-deficit energy diet. Fasting plasma glucose (FPG), oral glucose tolerance, glycated hemoglobin (A1c), fasting, and 2-h insulin were measured at baseline and at 16-week follow-up. Homeostasis model assessment (HOMA) 2 was calculated to estimate steady-state beta-cell function, insulin sensitivity, and insulin resistance. Our results showed significant reductions in fasting (P = 0.004) and 2-h plasma glucose (P = 0.01) after treatment, and significant improvements in beta-cell function (P = 0.03) and insulin resistance (P = 0.04) in the cabergoline group. The trend of non-significant A1c changes was decreasing in the cabergoline group versus an increasing trend in the placebo group. All anthropometric parameters were similar between the two groups. Our results revealed that twice-weekly cabergoline could improve glucose metabolism in prediabetes stage. Larger studies of longer duration are warranted to investigate the effect of cabergoline in preventing progression of prediabetes to type 2 diabetes mellitus.


Fatal insomnia and agrypnia excitata: sleep and the limbic system.
Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely consisting in an inability to sleep associated with motor and autonomic activation. Agrypnia excitata is the term which aptly defines this clinical condition, whose pathogenetic mechanism consists in an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from corticolimbic inhibitory control. Severance of cortical-subcortical limbic structures is due to visceral thalamus degeneration in fatal familial insomnia, and may depend on autoantibodies blocking voltage-gated potassium channels within the limbic system in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in delirium tremens. On the basis of these findings, we suggest that a neuronal network, extending from the medulla to the limbic cortex, controls the sleep-wake cycle, operating in an integrated fashion following a caudorostral organization.


[Use of complex preparations of cationic peptides in the treatment of acute pharyngitis].
Acute respiratory infections (ORI) consistently occupy one of the leading places among infectious and inflammatory diseases in children. Most often, antibacterial drugs are used to stop the inflammatory process in the pharynx. Cationic peptides have an extremely broad antimicrobial spectrum, rendering the effect not only in bacterial infections and mycoses, and protozoans. To demonstrate that the test drug is effective and safe for the treatment of acute viral pharyngitis in childhood. In the period from September 2019 to January 2020, 120 patients aged 6 to 18 years were treated with the drug «Doritricin» for viral pharyngitis. According to the research results it can be concluded that «Diretrizes» provides fast and high effect in pediatric practice.


Tumor-suppressing roles of miR-214 and miR-218 in breast cancer.
MicroRNAs (miRNAs) are small non-coding RNAs that are key post-transcriptional regulators of gene expression. MicroRNA-214 (miR-214) and microRNA-218 (miR-218) have shown the function of tumor suppressors in various types of human cancers. However, the biological functions of miR-214 and miR-218 in breast cancer have not been elucidated completely. The present study evaluated the expression and biological function of miR-214 and miR-218 in human breast cancer. Our results revealed that the expression of miR-214 and miR-218 were significantly decreased in breast cancer tissues compared with adjacent tissues. The aberrant expression of miR-214 and miR-218 were negatively associated with Ki-67, and the miR-218 expression was positively associated with progesterone receptor (PR) in breast cancer tissues. In vitro, the cell proliferation and migration were decreased, cell apoptosis was induced, and cell cycle was also disturbed in miR-214 or miR-218 overexpressed breast cancer cells. Our results demonstrated that miR-214 and miR-218 function as tumor suppressors in breast cancer, and may become biomarkers and potential therapeutic targets in breast cancer.


Sun Exposure in Pediatric Age: Perspective of Caregivers.
Excessive sun exposure during childhood increases the risk of skin cancer. This study characterized the knowledge and attitudes of caregivers regarding exposure and sun protection of children and adolescents. One hundred and ninety-eight caregivers (38.5 ± 8.0 years) who resorted to the consultations of a Pediatrics Service or a Family Health Unit answered a questionnaire. The age of children/adolescents was 6.5 ± 5.1 years. On average, caregivers presented a high level of knowledge regarding exposure and sun protection. One hundred and twenty-six caregivers indicated that they obtained more information about sun protection on social communication, and 66% considered the information provided by healthcare professionals to be enough. One-hundred and fifteen caregivers reported that the child/adolescent was more exposed to the sun after 4 a.m., and 88% reported applying sunscreen on the beach/pool and outdoor activities. Fifty-seven percent of caregivers renewed sunscreen application on the child/adolescent every 2 h, and 94% applied a sun protection factor ≥ 50 in the child/adolescent. There was a significant association (p < 0.001) between education level and caregivers' self-knowledge about sun protection (the higher the education, the higher the knowledge), and between the knowledge of the hour of sun exposure avoidance and the time when the child/adolescent was more exposed to the sun. This study shows that caregivers are highly knowledgeable about exposure and sun protection in children/adolescents, and their attitudes follow the general recommendations.


Defining estimands using a mix of strategies to handle intercurrent events in clinical trials.
Randomized controlled trials (RCTs) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the complete data to infer the treatment effect. However, intercurrent events (ICEs) including the use of concomitant medication for unsatisfactory efficacy, treatment discontinuation due to adverse events, or lack of efficacy may lead to interventions that deviate from the original treatment assignment. Therefore, defining the appropriate estimand (the appropriate parameter to be estimated) based on the primary objective of the study is critical prior to determining the statistical analysis method and analyzing the data. The International Council for Harmonisation (ICH) E9 (R1), adopted on November 20, 2019, provided five strategies to define the estimand: treatment policy, hypothetical, composite variable, while on treatment, and principal stratum. In this article, we propose an estimand using a mix of strategies in handling ICEs. This estimand is an average of the "null" treatment difference for those with ICEs potentially related to safety and the treatment difference for the other patients if they would complete the assigned treatments. Two examples from clinical trials evaluating antidiabetes treatments are provided to illustrate the estimation of this proposed estimand and to compare it with the estimates for estimands using hypothetical and treatment policy strategies in handling ICEs.


Unusual right pulmonary artery-to-left atrial communication associated with scimitar syndrome.
Right pulmonary artery to left atrial fistula is classified based on the right pulmonary artery branching, individual right pulmonary venous drainage, and presence of an aneurysmal segment. A rare association with scimitar syndrome and right lung devoid of blood supply from right pulmonary artery is described in this report. The anatomical and management differences between the different types are highlighted.


Viral fitness: history and relevance for viral pathogenesis and antiviral interventions.
The quasispecies dynamics of viral populations (continuous generation of variant genomes and competition among them) has as one of its frequent consequences variations in overall multiplication capacity, a major component of viral fitness. This parameter has multiple implications for viral pathogenesis and viral disease control, some of them unveiled thanks to deep sequencing of viral populations. Darwinian fitness is an old concept whose quantification dates back to the early developments of population genetics. It was later applied to viruses (mainly to RNA viruses) to quantify relative multiplication capacities of individual mutant clones or complex populations. The present article reviews the fitness concept and its relevance for the understanding of the adaptive dynamics of viruses in constant and changing environments. Many studies have addressed the fitness cost of escape mutations (to antibodies, cytotoxic T cells or inhibitors) as an influence on the efficacy of antiviral interventions. Here, we summarize the evidence that the basal fitness level can be a determinant of inhibitor resistance.


Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors.
Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a-j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC(50)=0.43+/-0.04microM) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46+/-3% change over the control) rather than the frequency rate (16+/-4% change over the control) at 100microM.


Complete Genome Sequence of Halopseudomonas aestusnigri Strain GOM5, Isolated from Asphalt Marine Sediments of the Gulf of Mexico.
We report here the complete genome sequence of a marine Halopseudomonas aestusnigri strain isolated from asphalt sediments of the Gulf of Mexico. Studying the genomes of atypical environmental bacteria increases knowledge about the biology of microorganisms metabolizing pollutants and is also a biotechnological resource to develop bioremediation methods.


Synopsis of the tribe Stipeae (Poaceae) in Nepal.
In Nepal the Stipeae consists of six genera: Achnatherum, Orthoraphium, Piptatherum, Ptilagrostis, Stipa, Trikeraia, and 15 species. Two new combinations, Ptilagrostis duthiei (Hook. f.) M.Nobis & P.D.Gudkova and Achnatherum staintonii (Bor) M.Nobis & P.D.Gudkova, are proposed, and new country records for Stipa klimesii, Ptilagrostis dichotoma, Ptilagrostis concinna and Achnatherum jacquemontii are reported. The records of Stipa roborowskyi, S. przewalskyi, S. capillata, S. consanguinea, S. mongholica, and S. sibirica, previously thought to occur in Nepal were based on misidentifications, and these have been excluded from the list of Nepalese Stipeae. We present keys for the identification of genera and species, and a checklist including information on nomenclatural types, regional and national distribution, and habitat. A lectotype is designated for Stipa brandisii Mez.


Possible interrelationship between changes in F-actin and myosin II, protein phosphorylation, and cell volume regulation in Ehrlich ascites tumor cells.
Osmotic shrinkage of Ehrlich ascites tumor cells (EATC) elicited translocation of myosin II from the cytosol to the cortical region, and swelling elicits concentration of myosin II in the Golgi region. Rho kinase and p38 both appeared to be involved in shrinkage-induced myosin II reorganization. In contrast, the previously reported shrinkage-induced actin polymerization [Pedersen et al. (1999) Exp. Cell Res. 252, 63-74] was independent of Rho kinase, p38, myosin light chain kinase (MLCK), and protein kinase C (PKC), which thus do not exert their effects on the shrinkage-activated transporters via effects on F-actin. The subsequent F-actin depolymerization, however, appeared MLCK- and PKC-dependent, and the initial swelling-induced F-actin depolymerization was MLCK-dependent; both effects were apparently secondary to kinase-mediated effects on cell volume changes. NHE1 in EATC is activated both by osmotic shrinkage and by the serine/threonine phosphatase inhibitor Calyculin A (CL-A). Both stimuli caused Rho kinase-dependent myosin II relocation to the cortical cytoplasm, but in contrast to the shrinkage-induced F-actin polymerization, CL-A treatment elicited a slight F-actin depolymerization. Moreover, Rho kinase inhibition did not significantly affect NHE1 activation, neither by shrinkage nor by CL-A. Implications for the possible interrelationship between changes in F-actin and myosin II, protein phosphorylation, and cell volume regulation are discussed.


Optical Coherence Tomography and Optical Coherence Tomography Angiography Findings in Multiple Sclerosis Patients.
In addition to ocular neurodegeneration in multiple sclerosis (MS), accompanying microvascular changes in the retina are thought to occur. In this study we sought to compare retinal neurodegenerative changes using optical coherence tomography (OCT) and microvascular changes using OCT angiography (OCTA) of MS patients and healthy controls. This cross-sectional study included 164 eyes of 83 MS patients and 114 eyes of 57 healthy control subjects. There were significant differences in retinal nerve fibre layer (RNFL), ganglion cell complex (GCC), and radial peripapillary capillary (RPC) vessel density (VD) between the MS group and the control group, but no significant differences in superficial capillary plexus (SCP) VD and deep capillary plexus (DCP) VD, foveal avascular zone (FAZ), non-flow area (NFA), and choriocapillary flow (CCF) values. Comparing the eyes with and without previous optic neuritis showed no significant differences in the OCT and OCTA measurements. A negative correlation was found between the expanded disability status scale score and disease duration and the RNFL and GCC values. A positive correlation was found between the RNFL and GCC values and the SCP VD and RPC VD. In MS patients, RPC VD values decreased in correlation with decreases in RNFL and GCC. This reduction increased as the disease duration and disability criteria increased. OCT and OCTA may be important biomarkers in MS.


The evolutionary origins of gene regulation.
One way that organisms cope with constantly changing physical and biological conditions is by regulating the expression of genes and thereby altering protein production. Clearly, altering the protein production to match the environmental demands can be adaptive, but there may be evolutionary barriers to the transition from constitutive expression to regulated expression. In particular, down-regulating a gene when it is not needed means that there will necessarily be a delay in protein production when the protein is up-regulated in the future. We develop a model of simple gene regulation in response to randomly changing environmental conditions. We calculate the long-term behavior of gene expression and determine the fitness consequences of changes in the gene regulation. We then embed this model into a population genetic framework in order to determine the conditions that allow populations to evolve environment-specific transcription rates. The population genetic model follows the evolutionary transition from constitutive expression to regulated expression. There are three distinct possible evolutionary outcomes. The gene may be stuck in the always on position, the gene may first evolve to an intermediate constitutive expression level and then evolve regulation, or regulation can evolve directly from the ancestral state in a smooth fashion. Regulation is most likely to evolve when the costs of mis-expression are low and the transcript decay rate is high. This suggests that genes that have less severe reductions in fitness when mis-expressed are more likely to initially evolve regulation.


Genetic Variability and Phylogenetic Relationships within Trypanosoma cruzi I Isolated in Colombia Based on Miniexon Gene Sequences.
Phylogenetic studies of Trypanosoma cruzi have identified the existence of two groups: T. cruzi I and T. cruzi II. There are aspects that still remain unknown about the genetic variability within the T. cruzi I group. Given its epidemiological importance, it is necessary to have a better understanding of T. cruzi transmission cycles. Our purpose was to corroborate the existence of haplotypes within the T. cruzi I group and to describe the genetic variability and phylogenetic relationships, based on single nucleotide polymorphisms (SNPs) found in the miniexon gene intergenic region, for the isolates from different hosts and epidemiological transmission cycles in Colombian regions. 31 T. cruzi isolates were molecularly characterized. Phylogenetic relationships within T. cruzi I isolates showed four haplotype groups (Ia-Id), associated with their transmission cycle. In previous studies, we reported that haplotype Ia is mainly associated with the domestic cycle and domiciliated Rhodnius prolixus. Haplotype Ib is associated with the domestic cycle and peridomestic cycle, haplotype Ic is closely related with the peridomestic cycle, and haplotype Id is strongly associated with the sylvatic cycle. The phylogenetic methodologies applied in this study are tools that bolster the associations among isolates and thus shed light on Chagas disease epidemiology.


Clonal Hematopoiesis and Epigenetic Age Acceleration in Elderly Danish Twins.
Clonal hematopoiesis of indeterminate potential (CHIP) is common in the elderly and has been reported to associate with accelerated epigenetic age (AgeAccel), especially intrinsic (ie, cell-type independent) AgeAccel and to a lesser degree extrinsic AgeAccel, which reflects the immune-cell composition of the peripheral blood. We investigated the association between CHIP occurrence and AgeAccel in 154 Danish twin pairs aged 73-90 years (mean 79), using both individual-level and intrapair analyses, the latter to control for shared genetic and environmental factors. Of 308 individuals, 116 carried a CHIP mutation. CHIP carriers had non-significantly increased AgeAccel compared with non-carriers; the strongest association was for the Intrinsic Epigenetic Age Acceleration (IEAA) estimator (CHIP carriers 1.4 years older, P = 0.052). In intrapair analyses, the extrinsic Hannum age estimator showed the strongest association (1.6 years older, P = 0.027). In mutation-specific analyses, TET2 mutations were associated with the extrinsic Hannum age estimator in both individual-level (3.0 years older, P = 0.003) and intrapair analyses (2.8 years older, P = 0.05). DNMT3A mutations were associated with IEAA in individual-level (1.9 years older, P = 0.034) but not intrapair analysis (0.9 years, P = 0.41). Analyses of logit-transformed variant allele frequency were generally consistent with these results. Together, these observations indicate that different factors may be driving the expansion of DNMT3A and TET2 clones, respectively. Finally, CHIP carriers accelerated in both the Hannum and the GrimAge age estimators did not have an increased mortality risk in our cohort followed for 22 years (HR = 1.02, P = 0.93), hence not replicating the stratification model proposed by Nachun et al.


Rotation- and scale-invariant texture features based on spectral moment invariants.
Moment invariants previously developed for the analysis of two-dimensional patterns and objects regardless of orientation, scale, and position are extended to the Fourier transform domain to quantify signatures of textures in the power spectrum of images. The moment invariants of the power spectrum, which we call spectral moment invariants (SMIs), systematically extract rotation- and scale-invariant texture features by complex spectral moments instead of by performing ad hoc measurements of the shape of the two-dimensional power spectrum as do most of the existing Fourier transform domain methods. To our knowledge, the method of using SMIs to quantify texture features is the first to extract invariant texture information directly from the Fourier spectrum. The discriminative capability of SMIs in recognizing rotation- and scale-independent texture features is demonstrated by texture classification experiments. The results indicate that algorithms using SMIs can achieve performances comparable with, or better than, those algorithms using the spatial or wavelet transform domain texture features.


Histone H1 is a specific repressor of core histone acetylation in chromatin.
Although a link between histone acetylation and transcription has been established, it is not clear how acetylases function in the nucleus of the cell and how they access their targets in a chromatin fiber containing H1 and folded into a highly condensed structure. Here we show that the histone acetyltransferase (HAT) p300/CBP-associated factor (PCAF), either alone or in a nuclear complex, can readily acetylate oligonucleosomal substrates. The linker histones, H1 and H5, specifically inhibit the acetylation of mono- and oligonucleosomes and not that of free histones or histone-DNA mixtures. We demonstrate that the inhibition is due mainly to steric hindrance of H3 by the tails of linker histones and not to condensation of the chromatin fiber. Cellular PCAF, which is complexed with accessory proteins in a multiprotein complex, can overcome the linker histone repression. We suggest that linker histones hinder access of PCAF, and perhaps other HATs, to their target acetylation sites and that perturbation of the linker histone organization in chromatin is a prerequisite for efficient acetylation of the histone tails in nucleosomes.


Research note: beta-adrenergic agonist effects on liver and breast muscle protein synthesis in female chicks.
The effect of administration of clenbuterol, a beta-adrenergic agonist, on live weight gain and protein synthesis of liver and breast muscle was investigated in 32 White Leghorn chicks. Protein synthesis was measured by injection of [3H]phenylalanine in a wing vein using the flooding dose method. No significant changes in body weight gain were caused by dietary administration of the beta-agonist at .25 mg/kg of diet from 3 to 6 wk of age, but fat retention in the liver and breast muscle was significantly reduced by the drug treatment. No stimulating effect on protein synthesis of the beta-agonist administration was found either in the breast muscle or in the liver. Protein synthesis in the breast muscle was unchanged whereas that in the liver was reduced significantly by feeding clenbuterol.


Measles, mumps, rubella, and varicella among service members and other beneficiaries of the Military Health System, 2010-2016.
Measles, mumps, rubella, and varicella (MMR/V) are highly communicable infectious diseases whose causative agents are spread through contact with contaminated surfaces or airborne droplets. Individuals at highest risk for MMR/V infections include infants, unvaccinated or inadequately vaccinated persons, individuals living in communities with low vaccination rates or in crowded and unsanitary conditions, and persons with compromised immune systems. During 2010-2016, there were 11 confirmed measles cases and 76 confirmed mumps cases among all Military Health System (MHS) beneficiaries. Only one of the confirmed cases of measles was in a service member. There were seven confirmed rubella cases among all MHS beneficiaries. Among service members, there were 62 confirmed cases of varicella during the surveillance period. The number of confirmed cases of varicella among service members dropped from 28 cases in 2010 and 27 cases in 2011 to seven confirmed cases in 2012. There were no confirmed cases of varicella among active and reserve component service members during 2013-2016. Recent trends in MMR/V in both military and civilian populations in the U.S. highlight the importance of primary and booster vaccinations.


Profile of atrial fibrillation inpatients: Cardiovascular risk factors and cardiac rehabilitation programme delivery and referral patterns.
Atrial fibrillation (AF) is increasingly common; however, the cardiovascular risk factor profile and the patterns of delivery and referral to cardiac rehabilitation (CR) in this population are poorly described. We conducted an audit of medical records (n = 145) of patients admitted with AF in one local health district in Sydney, Australia. Patients were aged a mean 72 years, and 51% were male. Lack of risk factor documentation was common. Despite this, 65% had two or more modifiable cardiovascular risk factors, including hypertension (63%) and hypercholesterolaemia (52%). Referral to Phase II CR occurred for 25% and was decreased with permanent AF diagnosis and increased with more risk factors. AF patients admitted to hospital have multiple cardiovascular risk factors but limited risk factor screening and/or referral to outpatient CR programmes.


Local Water Dynamics in Coacervated Polyelectrolytes Monitored Through Dynamic Nuclear Polarization-Enhanced H NMR.
We present the first study of quantifying the diffusion coefficient of interfacial water on polyelectrolyte surfaces of systems fully dispersed in bulk water under ambient conditions. Such measurements were made possible through the implementation of a recently introduced Dynamic Nuclear Polarization (DNP) technique to selectively amplify the nuclear magnetic resonance (NMR) signal of hydration water that is interacting with specifically located spin labels on polyelectrolyte surfaces. The merit of this novel capability is demonstrated in this report through the measurement of solvent microvisosity on the surface of two types of oppositely charged polyelectrolytes, when freely dissolved versus when complexed to form a liquid-liquid colloidal phase called complex coacervates. These complex coacervates were formed through electrostatic complexation between the imidazole-based cationic homopolymer poly(N-vinylimidazole) (PVIm), and anionic polypeptide polyaspartate (PAsp) in the pH range of 4.5 - 6.0, under which conditions the coacervate droplets are highly fluidic yet densely packed with polyelectrolytes. We also investigated the rotational diffusion coefficients of the spin labels covalently bound to the polyelectrolyte chains for both PVIm and PAsp, showing a 5 fold change in the rotational correlation time as well as anisotropy parameter upon coacervation, which represents a surprisingly small decrease given the high polymer concentration inside the dense microdroplets. For both DNP and ESR experiments, the polymers were covalently tagged with stable nitroxide radical spin labels (∼1 wt %) to probe the local solvent and polymer segment dynamics. We found that the surface water diffusion coefficients near uncomplexed PVIm and PAsp at pH 8 differ, and are around D∼1.3×10(-9)m(2) / s. In contrast, inside the complex coacervate phase, the water diffusion coefficient in the immediate vicinity of either polyelectrolyte was D∼ 0.25×10(-9)m(2) / s, which is about an order of magnitude smaller than the bulk water self diffusion coefficient, and yet orders of magnitude greater than that of associated, bound, hydration water. This observation suggests the existence of measurable water inside complex coacervates with relatively high diffusion and exchange dynamics, implying that water moves in nanometer-scale pore spaces as opposed to being structurally bound or even absent. We infer from our observation that the PVIm and PAsp chains are undergoing roughly pairwise association, so that largely charge neutralized species compose the concentrated, yet fluidic and partially hydrated coacervate cores.


Development and clinical use of an oral heat-inactivated whole cell pertussis vaccine.
An orally administered, killed whole cell pertussis vaccine was developed which proved to be safe and potent in animal experiments. This vaccine was studied in limited field trials in Austria. In these field trials 1 X 10(12) bacterial cells were given orally on days 2, 3, 4, and 5 after birth with an oral booster of 1 X 10(12) cells given at six weeks. This vaccine was tolerated without side effects in more than 20,000 newborns, did induce a specific immune response including anti-pertussis IgG in serum, anti-pertussis IgA in saliva and specific pertussis mitogen stimulation. This immune response occurred significantly earlier in the orally but not in the parenterally vaccinated group. In addition, anti-pertussis antibodies in saliva were not induced in the parenterally vaccinated group. Pertussis morbidity in 11,192 orally vaccinated infants was compared to 3496 infants who did not receive oral vaccination and was found to be significantly lower for up to one year. There was no overall difference between orally and non-orally vaccinated infants as far as pertussis hospitalization and verified pertussis infection after one year was concerned.


Temporal Augmentation: A Systematic Review.
Clinicians employ various modalities in order to achieve temporal augmentation; however, no literature comprehensively describes these methods or provides perspective on available options. Understanding the available methodologies for cosmetic temporal augmentation allows for improved patient satisfaction with limited risk of complications. To synthesize the available literature on cosmetic temporal augmentation, including all available methodologies, patient satisfaction data, and complication rates, as well as to identify gaps in the available literature to encourage further research. A literature search was performed using the databases PubMed, Ovid Medline, Cochrane Library, and Web of Science. Using the key terms "temporal" or "temple" and "augmentation" or "rejuvenation," all article formats presenting primary literature data involving cosmetic temporal augmentation were included. Articles not presenting patient data or not discussing cosmetic indications were eliminated. A total of 12 articles were deemed appropriate for analysis. Of the 12 articles included, 6 (50%) evaluated filler techniques, 3 discussed fat grafting (25%), and 3 reviewed solid implant (25%) techniques. Eight (67%) of these were retrospective reviews, with the remaining being prospective trials (33%). All studies found high patient satisfaction rates and a small number of complications with their respective methodology. Several methods are employed for cosmetic temporal augmentation, including various types of injectable fillers, solid implants, and fat grafting, with all reporting successful satisfaction and complication outcomes. Further research is necessary to properly compare these modalities. Clinician discretion should guide procedural choice until future well-controlled studies are able to provide standardized outcomes.


Body mass status of school children of Dera Ismail Khan, Pakistan.
Childhood obesity is a global epidemic involving both developed and developing countries. It is a stare of over-nutrition with long-term complications such as dyslipidemia, hypertension, and coronary artery disease and type-2 diabetes. Underweight is the result of under nutrition leading to reduction in growth and development of every body organ especially the Central Nervous System. Long-term under-nutrition causes failure in linear growth (height) of the child. Growth is further retarded by the repeated attacks of respiratory infections, diarrhea and anemia as a result of reduced immunity. This study was carried, out eight primary schools of Dera Ismail Khan (Private, semi government organizations, and welfare foundations) having mixed population with some of the wards belonging to high socioeconomic group. Thorough clinical examination excluded those suffering from chronic heath problems. Height and weight of each one was taken body mass index of determined according to 'Quatelet's' index. Body mass index number was plotted on the CDC S age and gender specific growth charts 2-20 years for BMI-for age percentile and body mass status (underweight, normal weight, overweight/at the risk of overweight and obese/overweight. Total 1338 school going children (6-11 years) were examined with 865 (67.75%) boys and 471 (35.25%) as girls. 13.39%, 72.15%, 8.83% and 5.61% as underweight, normal weight, overweight and obese respectively. Percentage of underweight was higher in girls (25%) than boys (13.22). Percentage of obesity was higher (5.17%) in boys than girls (1.39%). Awareness about balanced diet, improvement in the level of education and socioeconomic conditions, easy access to health facilities and prevention of the gender discrimination, are the remedial measures to be taken to redress the situation.


First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of preeclampsia and IUGR.
A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39). Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021) or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.


Cell-assembled graphene biocomposite for enhanced chondrogenic differentiation.
Graphene-based nanomaterials are increasingly being explored for use as biomaterials for drug delivery and tissue engineering applications due to their exceptional physicochemical and mechanical properties. However, the two-dimensional nature of graphene makes it difficult to extend its applications beyond planar tissue culture. Here, graphene-cell biocomposites are used to pre-concentrate growth factors for chondrogenic differentiation. Bone marrow-derived mesenchymal stem cells (MSCs) are assembled with graphene flakes in the solution to form graphene-cell biocomposites. Increasing concentrations of graphene (G) and porous graphene oxide (pGO) are found to correlate positively with the extent of differentiation. However, beyond a certain concentration, especially in the case of graphene oxide, it will lead to decreased chondrogenesis due to increased diffusional barrier and cytotoxic effects. Nevertheless, these findings indicate that both G and pGO could serve as effective pre-concentration platforms for the construction of tissue-engineered cartilage and suspension-based cultures in vitro.


[Surgical outcomes of second liver resections for recurrent hepatic metastases from colorectal cancer].
To compare the clinical efficacies and safety of primary versus second liver resection for recurrent colorectal metastases to liver. Between January 2000 and March 2011, a total of 126 patients underwent liver resections for metastases from colorectal cancer at our institution. Among these, 16 patients underwent repeat liver resections. The comparisons were made for primary and second liver resections in blood loss volume, complications, hospital stay, operative duration and 1, 3, 5- year survival rates. Compared with primary liver resection group, the 1, 3, 5-year survival rates of second liver resection group were 93.8%, 56.1% and 37.4% respectively. For second hepatectomy group, blood loss volume was (323.8 ± 230.9) ml, operative duration (216.9 ± 79.7) min, postoperative hospital stay (23.4 ± 13.9) days and complication rate 18.8%. Compared with primary hepatectomy, there was no difference between two groups. Second liver resection may provide long-term survival rates similar to those of primary liver resections. Repeat liver resection is warranted when potentially curative.


A Low Molecular Weight Polypeptide Which Accumulates upon Inhibition of Porphyrin Biosynthesis in Maize.
Levulinic acid, an inhibitor of porphyrin biosynthesis, causes marked accumulation of a low molecular weight polypeptide in greening maize (Zea mays L.) leaves. Additional compounds which interfere with porphyrin synthesis (e.g. aminooxyacetate, iron-chelators, 4,6-dioxoheptanoic acid) had a similar effect. The polypeptide accumulated in the cytosol and could not be detected in the plastid stroma. Its molecular weight was estimated as 4800 daltons by electrophoresis in sodium dodecyl sulfate-acrylamide gels containing urea and glycerol. The accumulation of the polypeptide did not result from inhibition of chlorophyll or protoheme syntheses. Compounds which caused its accumulation markedly reduced the activity of nitrite reductase. It is suggested that the accumulation is caused by inhibition of siroheme synthesis which interferes with the formation of nitrite or sulfite reductase.


The evolution of IgE-mediated type I hypersensitivity and its immunological value.
The allergic phenotype manifests itself in a spectrum of troublesome to life-threatening diseases, from seasonal hay fever, through the food allergies, atopic eczema, asthma, to anaphylaxis. Allergy, that is an overreaction to allergen in hypersensitive individuals, results from the production of IgE, mast cell and basophil sensitisation and degranulation, requiring a range of medications to manage the conditions. Yet it is highly likely that allergy evolved for a purpose and that allergic diseases are accidental consequences of an insufficiently regulated immune response. This article presents a viewpoint from which to restore the immunological reputation of the allergic phenotype. We consider the evolutionary origins of potential allergens, toxins and parasites, and how they might have influenced early-mammal species in existence when IgE first developed. We conclude that the allergic phenotype has likely saved the lives of many more mammals than have ever died from allergy, so justifying the positive role of IgE in our evolution.


Impaired generalization of reward but not loss in obsessive-compulsive disorder.
Generalizing from past experiences can be adaptive by allowing those experiences to guide behavior in new situations. Generalizing too much, however, can be maladaptive. For example, individuals with pathological anxiety are believed to overgeneralize emotional responses from past threats, broadening their scope of fears. Whether individuals with pathological anxiety overgeneralize in other situations remains unclear. The present study (N = 57) used a monetary sensory preconditioning paradigm with rewards and losses to address this question in individuals with obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD), comparing them to healthy comparison subjects (HC). In all groups, we tested direct learning of associations between cues and reward vs. loss outcomes, as well as generalization of learning to novel choice options. We found no differences between the three groups in the direct learning of stimuli with their outcomes: all subjects demonstrated intact stimulus-response learning by choosing rewarding options and avoiding negative ones. However, OCD subjects were less likely to generalize from rewards than either the SAD or HC groups, and this impairment was not found for losses. Additionally, greater deficits in reward generalization were correlated with severity of threat estimation, as measured by a subscale of the Obsessive Beliefs Questionnaire, both within OCD and across all groups. These findings suggest that a compromised ability to generalize from rewarding events may impede adaptive behavior in OCD and in those susceptible to high estimation of threat.


A unique exonic splicing mutation in the human androgen receptor gene indicates a physiologic relevance of regular androgen receptor transcript variants.
In a patient with partial androgen insensitivity syndrome (AIS), we identified a single inherited presumably silent nucleotide variation (AGC -> AGT) in exon 8 (codon 888) of the AR gene. However, in the patient's genital skin fibroblasts, a considerably shortened transcript of 5.5 kb (normal: 10.5 kb) was detected, which misses a part of exon 8 and a prominent portion of the 3'-untranslated region. The translation product includes eight missense amino acids from codon 886 onward followed by a premature stop codon. As shown by in vitro expression analysis, the mutant protein lacks any residual function. However, reverse transcribed PCRs and sequence data indicate the existence of two additional splicing variants of 6.4 kb and 7.8-kb length both in patient and normal control genital skin fibroblasts. These splicing variants comprise the complete coding region but a shortened 3'-untranslated region. Thus, a distinct alternative pre-messenger RNA-processing event leading to two additional transcripts occurs generally in genital skin fibroblasts. In addition, this process partially prevents aberrant splicing in the patient and produces a small fraction of normal, functionally intact AR-protein that could explain the partial masculinization in this patient. This first report of an exonic splicing mutation in the AR-gene indicates a physiologic relevance of the regular AR-messenger RNA variants with shortened 3'-untranslated regions and their functional translation products in human genital development.


Composition and antimicrobial activity of the leaf and twig oils of Litsea acutivena from Taiwan.
The chemical composition, and antimicrobial and anti-wood-decay fungal activities of the essential oils isolated from the leaves and twigs of Litsea acutivena of Taiwan were investigated. The essential oils from the fresh leaves and twigs were isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Ninety-five and fifty-two compounds were identified in the leaf and twig oils, respectively. The main components of the leaf oil were gamma-patchoulene (11.0%), delta-cadinene (6.3%), trans-muurola-3,5-diene (5.9%), and beta-selinene (5.3%), whereas the main components of the twig oil were tau-cadinol (13.1%), beta-selinene (9.6%), trans-beta-ocimene (6.2%) and alpha-cadinol (7.7%). Bioactivity studies demonstrated that twig oil had excellent antimicrobial and anti-wood-decay fungal activities, superior to those of the leaf oil. For the antimicrobial and anti-wood-decay fungal activities of the twig oil, the active compounds were determined to be tau-cadinol and alpha-cadinol.


Acute pesticide poisoning associated with use of a sulfotepp fumigant in a greenhouse--Texas, 1995.
Pesticide fumigants that eradicate pests but do not damage flowers or foliage can be used to protect market-ready florals. During November 1995, a pesticide applicator worker in Texas became ill during fumigation despite wearing the personal protective equipment (PPE) recommended on the fumigant product label. This report summarizes the results of the case investigation by the Texas Department of Health (TDH) and CDC's National Institute for Occupational Safety and Health (NIOSH) and a survey of growers about pesticide use. The findings indicate that the recommended PPE may be inadequate to protect workers using sulfotepp fumigants from pesticide poisoning.


Suppression of luteinizing hormone pulses by restriction of glucose availability is mediated by sensors in the brain stem.
The availability of metabolic fuels such as glucose is known to influence reproductive function. Peripheral administration of 2-deoxyglucose (2DG), a competitive inhibitor of glycolysis, inhibits pulsatile LH secretion in the rat and growth-retarded lamb. We hypothesized that such glucoprivic suppression of LH secretion is mediated by the lower brain stem, because studies of both ingestive and reproductive behavior implicate lower brain stem structures, such as the area postrema, as a site that is sensitive to glucose availability. In the present study, the effect of a 2DG infusion, targeted to the fourth ventricle, on pulsatile LH secretion was examined in male rats. The males were castrated or castrated and immediately implanted with testosterone. Blood samples were collected through an indwelling atrial cannula every 6 min for 4 h for LH determination. After the first hour of blood sampling, 2DG (4 or 40 mg/kg) was infused into the fourth ventricle at a flow rate of 0.2 microliter/min through a cannula that had been stereotaxically implanted 1 week before sampling. The high dose of 2DG (40 mg/kg), but not the low dose (4 mg/kg), suppressed pulsatile LH secretion and increased food intake in both castrated and testosterone-treated castrated rats. LH secretion and food intake were not affected by the infusion of xylose (40 mg/kg) as an isoosmotic control. The site specificity of the 2DG treatment was confirmed by histological examination after an isovolumetric infusion of dye (0.2 microliter/min). These results suggest that glucose availability could influence LH secretion as well as feeding through a central sensor in the lower brain stem and are consistent with the idea that the area postrema might be an important glucosensor involved in the modulation of LH secretion.


Struggling with perfectionism: When good enough is not good enough.
Perfectionism includes a tendency for high standards for self and others with a clear goal of successful performance in a variety of areas. A perfectionist often reacts with critical evaluations whenever performance falls below these standards. Moreover, perfectionists emphasize personal goals to gauge their worth, neglecting intimate bonds or openness to new experience. At the core of perfectionism lies a view of self as weak, flawed, and easily rejected. Perfectionism can result in chronic tendencies for emotional distress and interpersonal conflict. Treatment aims to explore personal views of self and others, viewing perfectionism as a form of maladaptive coping. When clients understand the role of perfectionism, they can discontinue striving to meet their extreme goals and unrealistic standards. The authors of the papers in the issue present their views on how to treat these maladaptive tendencies according to their preferred therapeutic orientation.


X-ray and ultrasound localization of non-palpable breast lesions and difficulties in management.
Seventy-four patients who have had biopsy of a non-palpable breast lesion are reviewed. A double-dye localization technique was used in 88% while in 12% localization of the lesion was best achieved by ultrasound mammography. Biopsy was successful in 70 patients (95%) at the first attempt. The overall incidence of malignancy was 20%, being greater in asymptomatic patients (32%) than in patients with mastalagia (16%). Re-excision of the biopsy site in these patients showed residual cancer in 33%. It is suggested that both careful examination of the operative specimen and postoperative mammography may be necessary to ensure that the original lesion has been removed. Re-excision of the biopsy site appears to be necessary when the histology is malignant.


Vertebrate endoderm development.
Endoderm, one of the three principal germ layers, contributes to all organs of the alimentary tract. For simplicity, this review divides formation of endodermal organs into four fundamental steps: (a) formation of endoderm during gastrulation, (b) morphogenesis of a gut tube from a sheet of cells, (c) budding of organ domains from the tube, and (d) differentiation of organ-specific cell types within the growing buds. We discuss possible mechanisms that regulate how undifferentiated endoderm becomes specified into a myriad of cell types that populate the respiratory and gastrointestinal tracts.


Can Excess Glucocorticoid, Predispose to Cardiovascular and Metabolic Disease in Middle Age?
For many years, both human and animal studies correlated changes in behaviour of the young offspring with the degree of maternal stress or glucocorticoid exposure of the foetus/neonate. In the past ten years there has been overwhelming epidemiological evidence to suggest that growth retardation in utero is a very important risk factor for the development of cardiovascular and metabolic disease in adult life. More recently, it has been shown that one important, even key, determinant is the exposure of the foetus to excess glucocorticoid. Even a brief period (48 h) of dexamethasone exposure very early in pregnancy was able to programme permanently hypertensive adult sheep. Understanding how such programming works, and the underlying physiological changes that occur, provides one of the most exciting challenges in contemporary endocrinology and developmental biology.


Allee effects can both conserve and create spatial heterogeneity in population densities.
In order to determine conditions which allow the Allee effect (caused by biparental reproduction) to conserve and create spatial heterogeneity in population densities, we studied a deterministic model of a symmetric two-patch metapopulation. We proved that under certain conditions there exist stable equilibria with unequal population densities in the two patches, a situation which can be interpreted as conserved heterogeneity. Furthermore, the Allee effect can lead to instability of the equilibrium with equal population densities if some degree of competition is assumed to occur between the subpopulations (non-local competition). This indicates the potential of the Allee effect to create spatial heterogeneity. Neither of these effects appear under biologically realistic parameter values in a model where uniparental reproduction is assumed. We proved that both the between-patch migration intensity and the degree of non-local competition are decisive in determining boundaries between these types of behaviour of the spatial system with Allee effect. Therefore, we propose that the Allee effect, migration intensity, and non-local competition should be considered jointly in studies focusing on problems like pattern formation in space and invasions of spreading species.


NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth.
Reactive oxygen species produced by NADPH oxidase are involved in the neuronal death associated with various neurodegenerative disorders. However, the role of NADPH oxidase in neuronal differentiation has not been well characterized. In nondifferentiated PC12 cells, the mRNA level of NOX1, a catalytic subunit of NADPH oxidase expressed in nonphagocytes, was approximately 10 times higher than that of the phagocyte type subunit, NOX2 (gp91(phox)), while the transcript of another isoform, NOX4, was not detected. Following nerve growth factor (NGF)-induced neurite outgrowth, the mRNA level of NOX1 and NOX2 was progressively increased and decreased, respectively. The NGF-induced increase in NOX1 mRNA was mediated by TrkA and accompanied by increased intracellular superoxide, which was suppressed by NADPH oxidase inhibitors. Unexpectedly, these inhibitors and superoxide scavengers significantly enhanced NGF-induced neurite outgrowth. Enhanced neurite outgrowth was similarly demonstrated in cells depleted with the NOX1 transcript by stable expression of ribozymes targeted for the NOX1 mRNA sequence. Furthermore, NGF-induced expression of betaIII-tubulin was significantly augmented in cells treated with NADPH oxidase inhibitors or stably expressing ribozymes. Phosphatidylinositol-3 (PI3) kinase inhibitors, without affecting NGF-induced NOX1 expression, augmented NGF-induced neurite outgrowth but not in clones expressing ribozymes. Taken together, increased superoxide production by up-regulation of NOX1 may negatively regulate neuronal differentiation by suppressing excessive neurite outgrowth.


The alerting effects of short and long naps in narcoleptic, sleep deprived, and alert individuals.
Eleven narcoleptic patients and 22 age- and gender-matched normal controls participated in a study to determine the alerting effects of differing nap lengths. All narcoleptic patients had been previously diagnosed [mean sleep latency on the multiple sleep latency test (MSLT) < or = 5 minutes with two or more sleep-onset rapid eye movement periods (SOREMPs)]. Healthy, normal subjects with a mean sleep latency on the screening MSLT > or = 8 minutes were randomly assigned to one of two groups (i.e. sleep-deprived and alert). All subjects completed two experimental night and days with at least 5 days between sessions. On the evening prior to each experimental day, narcoleptic and alert subjects spent 8 hours in bed and sleep-deprived subjects spent 0 hours in bed. The following day, all subjects underwent one of two napping conditions, 15 or 120 minutes in bed. Both naps were terminated at noon. Every subject underwent both conditions and the order of conditions was counterbalanced. From 1215 to 1355 hours all subjects underwent a modified MSLT. At 1500 hours, the subjects had a 1-hour nap. The results showed that the 120-minute nap condition was more beneficial than the 15-minute nap. Narcoleptic and sleep deprived subjects were shown to have comparable levels of sleepiness on the modified MSLT. However, a differential response pattern on their latency to sleep was noted on the 1-hour nap. Sleep-deprived subjects were shown to be differentially more alert following a 120-minute nap opportunity. In contrast, for narcoleptic patients the beneficial effects of the nap were lost when tested 3 hours later. These results show that narcoleptic patients benefit from a longer nap but that these benefits are short-lived.


Photosynthesis and inorganic carbon transport in isolated asparagus mesophyll cells.
The possibility of HCO(3) (-) transport into isolated leaf mesophyll cells of Asparagus sprengeri Regel has been investigated. Measurement of the inorganic carbon pool in these cells over an external pH range 6.2 to 8.0, using the silicone-fluid filtration technique, indicated that the pool was larger than predicted by passive (14)CO(2) distribution, suggesting that HCO(3) (-) as well as CO(2) crosses the plasmalemma. Intracellular pH values, calculated from the distribution of (14)CO(2) between the cells and the medium, were found to be higher (except at pH 8.0) than those previously determined by 5,5-dimethyl[2-(14)C]oxazolidine-2,4-dione distribution. It is suggested that the inorganic carbon accumulated above predicted concentrations may be bound to proteins and membranes and thus may not represent inorganic carbon actively accumulated by the cells, inasmuch as in a closed system at constant CO(2) concentration, the photosynthetic rates at pH 7.0 and 8.0 were 5 to 8 times lower than the maximum rate which could be supported by CO(2) arising from the spontaneous dehydration of HCO(3) (-). Furthermore, CO(2) compensation points of the cells in liquid media at 21% O(2) at pH 7.0 and 8.0, and the K((1/2)) CO(2) (CO(2) concentration supporting the half maximal rate of O(2) evolution) at 2% O(2) at pH 7.0 and 8.0 are not consistent with HCO(3) (-) transport. These results indicate that the principal inorganic carbon species crossing the plasmalemma in these cells is CO(2).


Macrophage and osteoblast responses to biphasic calcium phosphate microparticles.
The aim of this work was to investigate in vitro the biological events leading to ectopic bone formation in contact with microporous biphasic calcium phosphate (BCP) ceramics. After implantation, microparticles may arise from their degradation and induce an inflammatory response involving macrophages. The secretion of pro-inflammatory cytokines may affect the differentiation of osteoblasts. Mouse macrophage-like (J774) and osteoblast-like (MC3T3-E1) cells were cultured in the presence of BCP microparticles of different sizes (<20, 40-80, or 80-200 microm). The smallest microparticles decreased the viability of both cell types as measured with LDH and methyl tetrazolium salt assays, and enhanced the secretion of pro-inflammatory cytokines (IL-6 and TNF-alpha) by macrophages after 24 h, as revealed by ELISA. Osteoblastic cells were then cultured for 96 h in the presence of these pro-inflammatory cytokines and their differentiation studied by RT-PCR. MC3T3-E1 cells cultured with TNF-alpha showed a decrease in osterix, PTH receptor (PTHR1), and osteocalcin gene expression. On the contrary, IL-6 enhanced the expression of osterix, Runx2, alkaline phosphatase, and osteocalcin compared with plastic. In conclusion, this study shows that the inflammatory response initiated by BCP microparticles may have both detrimental and beneficial effects on osteogenesis.


Localization of multidrug transporter substrates within model membranes.
Active extrusion of drugs from the cell interior by primary and secondary efflux pumps is an essential mechanism underlying the phenomenon of multidrug resistance. The first discovered and best characterized primary efflux pump found in humans is the ABC transporter P-glycoprotein (PGP), which shows very broad substrate specificity. Many of these molecules are lipophilic, and binding most likely takes place within the membrane. PGP could either translocate them from the inner to the outer leaflet (flippase) or extrude them from the membrane into the extracellular environment (hydrophobic vacuum cleaner). Recognition and binding of such a diverse set of substrates must be associated with a preferred membrane location, determined by molecular properties and lipid interactions. Therefore, a systematic study of the interaction among seven PGP substrates (phenazine, doxorubicin, cephalexin, ampicillin, chloramphenicol, penicillin G, and quercetin) and two modulators (quinidine and nicardipine) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) model membranes is reported here. The location profile of these molecules across the membrane was determined by (1)H NOESY MAS NMR based on (1)H-(1)H cross-peaks between their aromatic fingerprint region and lipid resonances. Although structurally rather diverse, all tested substances are found to have their highest concentration between the phosphate of the lipid headgroup and the upper segments of the lipid hydrocarbon chains. Our findings are consistent with PGP substrate and modulator binding from the membrane interface region.


Low Magnetic Damping of Ferrimagnetic GdFeCo Alloys.
We investigate the Gilbert damping parameter α for rare earth (RE)-transition metal (TM) ferrimagnets over a wide temperature range. Extracted from the field-driven magnetic domain-wall mobility, α was as low as the order of 10^{-3} and was almost constant across the angular momentum compensation temperature T_{A}, starkly contrasting previous predictions that α should diverge at T_{A} due to a vanishing total angular momentum. Thus, magnetic damping of RE-TM ferrimagnets is not related to the total angular momentum but is dominated by electron scattering at the Fermi level where the TM has a dominant damping role. This low value of the Gilbert damping parameter suggests that ferrimagnets can serve as versatile platforms for low-dissipation high-speed magnetic devices.


Utilization of lipids during aestivation of the African lungfish, Protopterus annectens.
Sequential alterations of body weights as well as total lipids, triglycerides, cholesterol and ketone body levels in the blood of Protopterus annectens during twelve month duration of aestivation were investigated. The results revealed that after the first trimester of dormancy, there was significant body weight reduction (p < 0.05) coupled with significant hypolipodaemia, hypotriacylgly-cerolaemia and hypocholesterolaemia respectively (p < 0.05) but without significant ketonaemia (p < 0.05). The total lipid, triglyceride, cholesterol and body weight reductions continued through the second, third and fourth trimesters of aestivation respectively (p < 0.05) but with serum ketone body levels remaining unaltered (p < 0.05). Thus, the utilization of lipids as a source of energy during aestivation of P. annectens does not lead to ketone body accumulation.


Controlling the composition of a confined fluid by an electric field.
Starting from a generic model of a pore/bulk mixture equilibrium, we propose a novel method for modulating the composition of the confined fluid without having to modify the bulk state. To achieve this, two basic mechanisms-sensitivity of the pore filling to the bulk thermodynamic state and electric field effect-are combined. We show by Monte Carlo simulation that the composition can be controlled both in a continuous and in a jumpwise way. Near the bulk demixing instability, we demonstrate a field induced population inversion in the pore. The conditions for the realization of this method should be best met with colloids, but being based on robust and generic mechanisms, it should also be applicable to some molecular fluids.


Growth performance and health status in weanling piglets fed spray-dried porcine plasma under typical Northern European conditions.
The effect of inclusion of spray-dried porcine plasma (SDPP) in diets for weanling piglets was studied. The objectives were to determine whether SDPP would have positive effects on post-weaning piglet performance and health under typical Northern European conditions. In experiment 1, 160 weanling piglets were assigned randomly to a control diet or a diet containing 3% SDPP, which was added at the expense of both fishmeal and dried skim milk. In experiment 2, 264 weanling piglets were assigned to a control diet containing whey protein, a diet without whey protein but with SDPP or a diet containing both whey protein and SDPP. In essence, SDPP was added to the test diets at the expense of either whey protein or fishmeal. Piglets were fed the diets for 3 weeks. In experiment 1, the piglets fed the SDPP diet had a 7% higher average daily gain (ADG) and a 4% lower feed conversion ratio (FCR) (p < 0.05) during the first 3 weeks after weaning than did those fed the control diet. There were no differences in leucocyte counts or gamma-globulin. In experiment 2 there were no significant differences in ADG and FCR among the dietary treatments. It is concluded that low amounts of SDPP in weanling diets can have positive effects on growth performance under Northern European conditions.


Interpersonal problems, optimism and coping styles among women with conversion disorder: A correlational study.
To explore the relationship of interpersonal problems, optimism and coping styles among women with conversion disorder. The correlational study was conducted from August to October 2017 at different hospitals in Lahore, Pakistan, and comprised 50 women aged 12-60 years who had been diagnosed with conversion disorder. The translated version of Interpersonal Problem-32, brief version of Coping Orientation to Problems Experienced, and Life Orientation Test-Revised tools were used to collect data and to assess the relationship of optimism, interpersonal problems, optimism and copying styles. Data was analysed using SPSS 23. Of the 50 women approached, 49(98%) responded on variables questionnaires with a mean age of 24.44±10.29. Among the total, 20(40%) belonged to very low socioeconomic class and 17(34%) belonged to the low socioeconomic class. An inverse relationship was found between the variables of interpersonal problems and optimism (r= -0.067). Self-blaming coping style was significantly correlated with the disorder (r=0.294; p<0.05). Positive relationship was also found between coping by emotional support (r=0.198) and pessimism (r=0.018). Social inhibition had positive correlation with behavioural disengagement (r=0.122). Social inhibition self-blaming non-adaptive ways, pessimism, optimism and the interpersonal problem of behavioural disengagement were found to be associated with each other among women with conversion disorder.


Offering the option of randomized clinical trials to cancer patients who overestimate their prognoses with standard therapies.
We have shown that cancer patients' routine (and understandable) overestimations of their prognoses with standard therapy may inhibit their accrual to randomized clinical trials for which standard therapies are the alternative. Patients' appreciation of the rationale for a trial, and the potential benefit of trial participation, can only be enhanced if they understand their prognoses with standard therapy. However, clinical investigators may be reluctant to provide specific information that deflates patients' estimates of their prognoses. The routine withholding of information regarding the modest benefits of standard therapies may avoid patient distress, but such physician behavior is paternalistic and may deleteriously affect trial accrual. On the other hand, the routine communication of prognostic information will cause significant distress among patients and will perhaps be destabilizing to that minority of patients who would otherwise shun this information or truly cannot psychologically tolerate it. A middle ground between these extremes is the stepwise disclosure of potentially distressing information, wherein specific prognostical information is offered by physicians to patients and actually provided or communicated only after patients first understand the nature of it and then indicate their interest in receiving it. A practical disadvantage of this approach is its additional demand on physicians' time. Therefore, if impracticality is to be avoided and yet the approach fostered, clinical investigators might consider developing trial-specific, written or audiovisual materials for patient education about general background information. These could be employed prior to patient-physician dialogue and so enable physicians to focus on more sensitive subjects, such as prognosis with standard therapy.


Granulomatous rosacea-like leukemid in a patient with acute myeloid leukemia.
Skin findings in leukemias may be divided into specific lesions (leukemia cutis) and non-specific lesions (leukemids) which may be found in up to 80% of all patients with leukemias. The leukemids vary clinically and they are usually a manifestation of bone marrow or immunologic impairment, but also Sweet syndrome, pyoderma gangrenosum, erythroderma, maculopapular exanthema, prurigo-like papules, generalized pigmentation, follicular mucinosis, generalized pruritus may be found during the course of leukemia. We report a 70-year-old male with a 3-month history of erythema, papules and pustules on the face, ears and neck and over a month history of refractory anemia, anorexia, weight loss, malaise, and fever. Physical examination revealed symmetric erythematous, violaceous papules, papulo-nodules and plaques with slate scale and sparse, small pustules on the face, earlobes and neck. Histopathologic findings of involved skin showed diffuse mixed inflammatory cell infiltrate with perifollicular accentuation and focal granulomatous inflammation in the papillary and upper reticular dermis. Extensive checkup revealed the presence of acute myeloid leukemia French-American-British (FAB) classification subtype M2, with signs of three-lineage dysplasia. The patient was treated by L6 protocol which led to complete remission, both in bone marrow and skin, but after seven months he had relapse of leukemia with the fatal outcome. This case indicates the importance of skin eruptions in the context of hematological malignancies.


Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression.
Maintenance of pluripotency and specification towards a new cell fate are both dependent on precise interactions between extrinsic signals and transcriptional and epigenetic regulators. Directed methylation of cytosines by the de novo methyltransferases DNMT3A and DNMT3B plays an important role in facilitating proper differentiation, whereas DNMT1 is essential for maintaining global methylation levels in all cell types. Here, we generated single-cell mRNA expression data from wild-type, DNMT3A, DNMT3A/3B and DNMT1 knockout human embryonic stem cells and observed a widespread increase in cellular and transcriptional variability, even with limited changes in global methylation levels in the de novo knockouts. Furthermore, we found unexpected transcriptional repression upon either loss of the de novo methyltransferase DNMT3A or the double knockout of DNMT3A/3B that is further propagated upon differentiation to mesoderm and ectoderm. Taken together, our single-cell RNA-sequencing data provide a high-resolution view into the consequences of depleting the three catalytically active DNMTs in human pluripotent stem cells.


Retinal Sensitivity Correlates With the Superficial Vessel Density and Inner Layer Thickness in Diabetic Retinopathy.
The purpose of this paper was to present our study on the relationship between the parafoveal sensitivity measured using microperimetry and the vessel density (VD) assessed by optical coherence tomography-angiography (OCT-A) in eyes with diabetic retinopathy (DR). The observational case series was conducted in a tertiary ophthalmology center. Eyes with DR and without macular edema were consecutively included. All eyes underwent microperimetry and OCT-A. The correlation between the regional retinal sensitivity and the corresponding local capillary changes and structural alterations seen on OCT-A was assessed in each retinal quadrant. Thirty-seven eyes of 21 patients were included. The mean retinal sensitivity was 28.7 ± 2 decibel (dB). The mean parafoveal VD was 43.2 ± 4.2% in the superficial capillary plexus (SCP) and 48.1 ± 3.3% in the deep capillary complex (DCC). In the multivariate linear regression model, the mean retinal sensitivity was positively correlated with the VD in the SCP in the parafoveal ring (P = 0.01) and with the inner nuclear layer (INL) thickness (P = 0.01). The qualitative analysis of each quadrant showed the presence of areas of capillary dropout with a normal sensitivity. Conversely, all areas of decreased sensitivity (<25 dB) were associated with a decreased VD in the SCP and the DCC. The parafoveal sensitivity positively correlated with the VD in the SCP in DR eyes. Areas with a low retinal sensitivity were always co-located with a loss of capillaries in the SCP and the DCC despite preserved outer retinal layers.


Improving Quality and Efficiency in Pediatric Emergency Department Behavioral Health Care.
Many children with behavioral health concerns increasingly utilize the emergency department for assessment and care. These visits are increasing in frequency, length, and cost, further stressing already limited resources. To improve the quality of care in this population, we developed a multidisciplinary improvement initiative to decrease the length of stay by 10% (from 5.2 hours), increase suicide screening to 90%, and improve patient and family experience by 10% (from 89.7). We leveraged a multidisciplinary team to map care processes, standardize suicide risk screening, optimize staffing, and develop a brochure to demystify patients' and families' visits. We developed dashboards and a call-back system following discharge to understand engagement in post-acute care plans. We utilized run charts to identify signals of nonrandom variation. We reduced overall length of stay from 5.2 to 4 hours, improved patient experience scores from 89.7 to 93.2, and increased the suicidality screening rate from 0% to 94%. There was no change in the 72-hour return rate in this population. Engagement of a multidisciplinary team, with strategic implementation of improvements, measurably improved many aspects of care for pediatric patients with behavioral health crises in the emergency department setting. Recidivism, however, remains unchanged in this population and continues as a goal for future work.


Oxidative Stability of Vegetal Oil-Based Lubricants.
Lipids are widely distributed in nature and are one of the most important components of natural foods, synthetic compounds, and emulsions. To date, there is a strong social demand in the industrial sector for the use of sustainable products with a minimal environmental impact. Depending on their origin and composition, lipids can be employed as a plausible alternative as biodegradable lubricants in order to reduce the use of conventional mineral oil lubricants and mitigate their environmental impact. This perspective provides an overview of the advantages and constrains of vegetal oils under different lubrication regimes and the tribochemical reactions that can take place. Also, the different factors and pathways that influence their oxidation, the key role of moisture, and the changes of physical properties under pressure and temperature are reviewed. Special emphasis is devoted to the oxidation instability of fatty acids and vegetal oils and the physical and chemical approaches to improve oxidative and thermal stability are described in detail.


Unraveling Reticulate Evolution in Opuntia (Cactaceae) From Southern Mexico.
The process of hybridization occurs in approximately 40% of vascular plants, and this exchange of genetic material between non-conspecific individuals occurs unequally among plant lineages, being more frequent in certain groups such as Opuntia (Cactaceae). This genus is known for multiple taxonomic controversies due to widespread polyploidy and probable hybrid origin of several of its species. Southern Mexico species of this genus have been poorly studied despite their great diversity in regions such as the Tehuacán-Cuicatlán Valley which contains around 12% of recognized Mexico's native Opuntia species. In this work, we focus on testing the hybrid status of two putative hybrids from this region, Opuntia tehuacana and Opuntia pilifera, and estimate if hybridization occurs among sampled southern opuntias using two newly identified nuclear intron markers to construct phylogenetic networks with HyDe and Dsuite and perform invariant analysis under the coalescent model with HyDe and Dsuite. For the test of hybrid origin in O. tehuacana, our results could not recover hybridization as proposed in the literature, but we found introgression into O. tehuacana individuals involving O. decumbens and O. huajuapensis. Regarding O. pilifera, we identified O. decumbens as probable parental species, supported by our analysis, which sustains the previous hybridization hypothesis between Nopalea and Basilares clades. Finally, we suggest new hybridization and introgression cases among southern Mexican species involving O. tehuantepecana and O. depressa as parental species of O. velutina and O. decumbens.


Analysis of phenylpiperazine-like stimulants in human hair as trimethylsilyl derivatives by gas chromatography-mass spectrometry.
A simple and sensitive procedure, using p-tolylpiperazine (pTP) as internal standard (IS), has been developed and validated for the qualitative and quantitative analysis of 1-(3-trifuoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) in hair. Drug extraction was performed by incubation with 1 M sodium hydroxide at 50°C for 40 min, and the extracts were cleaned up using mixed-mode solid-phase extraction. The analytes were derivatized with N-methyl-N-(trimethylsilyl) trifluoroacetamide with 5% trimethylchlorosilane and analysed by gas chromatography-mass spectrometry in the selected ion monitoring mode. The method was linear from 0.05 (lower limit of quantitation) to 4 ng mg(-1), with correlation coefficients higher than 0.99 for all the compounds. Intra- and interday precision and accuracy were in conformity with the criteria normally accepted in bioanalytical method validation, and the sample cleanup step presented a mean efficiency higher than 90% for all the analytes. Due to its simplicity and speed, this method can be successfully applied in the screening and quantitation of these compounds in hair samples, and is suitable for application in forensic toxicology routine analysis.


The effects of cystoscopy and hydrodistention on symptoms and bladder capacity in interstitial cystitis/bladder pain syndrome.
The use of cystoscopy and hydrodistention in the management of interstitial cystitis/bladder pain syndrome (IC/BPS) varies widely between providers. Current evidence regarding the risks and benefits of hydrodistention, as well as the long term effects of repeated hydrodistention are not well established. We sought to characterize the effects of hydrodistention on IC/BPS symptoms as well as bladder capacity. We retrospectively queried our institutional records for patients with non-ulcerative IC/BPS who underwent hydrodistention over an 11-year period to obtain demographic and clinical factors at the time of diagnosis and treatment. Symptom relief and bladder capacity changes were assessed, and multivariable models were used to predict response to treatment. There were 328 patients who underwent hydrodistention during the study period, of whom 36% received the procedure multiple times, and overall median follow-up was 38.6 months. Patients with repeated hydrodistentions were more likely to be female, have more comorbid pain disorders, and have trialed anticholinergic medications and intravesical instillations. No decrease in mean bladder capacity was observed over time (P = 0.40). Significant decreases in symptom scores were observed following the procedure on multiple questionnaires. Hydrodistention does not decrease bladder capacity even with multiple procedures, and measurably improves symptoms in some patients with IC/BPS. Continuing efforts to better identify those patients most likely to benefit from this procedure are justified.


Evaluation of a case of diffuse large B-cell lymphoma.
Lymphomas are a group of malignant blood cell tumors that develop from lymphocytes representing 2.2% of all malignant neoplasms of the head and neck. Two main categories of lymphomas are Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) of which 90% are of the NHL type. Several classification systems have existed for lymphomas, the objectives of which are to help in identification of homogeneous group of well-defined entities and facilitating the recognition of uncommon diseases that require further classification as it affects prognosis and therapeutic implications. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL in the oral cavity involving Waldeyer's ring, base of the tongue, buccal mucosa and hard palate. DLBCL can be divided into germinal center B-cell-like, activated B-cell-like or type 3 gene expression profiles. This paper highlights a case report of DLBCL revisiting the intricacies and difficulties involved in establishing a diagnosis.


Police applicant response bias on the California Psychological Inventory.
Positive response bias is common under the high demand conditions of personnel selection. This study investigated positive response bias on the California Psychological Inventory (CPI)-434 by police officer applicants as scored by the CPI-434-Police and Public Safety Report. Police officer applicants completed the CPI-434 under high and then again under low demand conditions. The high demand condition was represented by the CPI administration as part of the preemployment psychological evaluation. The low demand condition was represented by a CPI administration with no contingencies approximately 4 months later during the police academy. Demand effects were illustrated by comparing applicant scores (within-subject) under high versus low demand conditions on CPI-Police and Public Safety Report (CPI-PPSR) prediction equations and CPI scales. Significant demand effects were observed on 23 of 46 comparisons. Modest support for the construct validity of the Good Impression (Gi) scale and somewhat less for the Fake Good Index as measures of positive response bias were observed. Response bias potential impact on police officer performance predictions was discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The risk associated with hyperoncotic colloids in patients with shock.
Crystalloids, artificial and natural colloids have been opposed as representing different strategies for shock resuscitation, but it may be relevant to distinguish fluids based on their oncotic characteristics. This study assessed the risk of renal adverse events in patients with shock resuscitated using hypo-oncotic colloids, artificial hyperoncotic colloids, hyperoncotic albumin or crystalloids, according to physician's choice. International prospective cohort study including 1,013 ICU patients needing fluid resuscitation for shock. Patients suffering from cirrhosis or receiving plasma were excluded. Influence of different types of colloids and crystalloids on the occurrence of renal events (twofold increase in creatinine or need for dialysis) and mortality was assessed using multivariate analyses and propensity score. Statistical adjustment was based on severity at the time of resuscitation, risks factor for renal failure, and on variables influencing physicians' preferences regarding fluids. A renal event occurred in 17% of patients. After adjustment on potential confounding factors and on propensity score for the use of hyperoncotic colloids, the use of artificial hyperoncotic colloids [OR: 2.48 (1.24-4.97)] and hyperoncotic albumin [OR: 5.99 (2.75-13.08)] was significantly associated with occurrence of renal event. Overall ICU mortality was 27.1%. The use of hyperoncotic albumin was associated with an increased risk of ICU death [OR: 2.79 (1.42-5.47)]. This study suggests that harmful effects on renal function and outcome of hyperoncotic colloids may exist. Although an improper usage of these compounds and confounding factors cannot be ruled out, their use should be regarded with caution, especially because suitable alternatives exist.


[Spatiotemporal dynamics of vegetation cover based on trajectory change detection: a case study in Dapeng Peninsula of Shenzhen].
By using the second-time developed ArcEngine component at pixel level, this paper studied the spatiotemporal dynamics of vegetation cover in the Dapeng Peninsula of Shenzhen, China in 1986-2007, and analyzed the characters and causes of the dynamics. To quantify this dynamics, the NDVI changes in 1986-2007 were extracted from 10 time-series TM/ETM+ remote sensing images, and the results showed that from 1986 to 2007, there were four trajectories of vegetation cover change in the Peninsula, including stable (a), stable-rising-stable (aba), stable-descending-stable (aca), and stable-descending-stable-rising-stable (acaba). The area with these four types occupied 71.54% of the total. Among the four types, type "a" was most common, occupying 1/3 of the study area, mainly in the mountains; and type "acaba" was the typical one, which was closely related to the deforestation and reforestation after the human disturbances of original vegetation. The areas at higher elevation or steeper slopes exhibited smaller vegetation change, mainly because of the constrained human disturbances. Timing of the vegetation cover change showed a relative stability in the mid-90s of 20th century, but a dramatic change after 2003, coinciding with the growth of Shenzhen City.


Neurofunctional mapping of reward anticipation and outcome for major depressive disorder: a voxel-based meta-analysis.
Aberrations in how people form expectations about rewards and how they respond to receiving rewards are thought to underlie major depressive disorder (MDD). However, the underlying mechanism linking the appetitive reward system, specifically anticipation and outcome, is still not fully understood. To examine the neural correlates of monetary anticipation and outcome in currently depressed subjects with MDD, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies using the monetary incentive delay task. During reward anticipation, the depressed patients exhibited an increased response in the bilateral middle cingulate cortex (MCC) extending to the anterior cingulate cortex, the medial prefrontal cortex, the left inferior frontal gyrus (IFG), and the postcentral gyrus, but a reduced response in the mesolimbic circuit, including the left striatum, insula, amygdala, right cerebellum, striatum, and IFG, compared to controls. During the outcome stage, MDD showed higher activity in the left inferior temporal gyrus, and lower activity in the mesocortical pathway, including the bilateral MCC, left caudate nucleus, precentral gyrus, thalamus, cerebellum, right striatum, insula, IFG, middle frontal gyrus, and temporal pole. Our findings suggest that cMDD may be characterised by state-dependent hyper-responsivity in cortical regions during the anticipation phase, and hypo-responsivity of the mesocortico-limbic circuit across the two phases of the reward response. Our study showed dissociable neural circuit responses to monetary stimuli during reward anticipation and outcome, which help to understand the dysfunction in different aspects of reward processing, particularly motivational v. hedonic deficits in depression.


Photon-counting polarizing radiometer.
Photon counting is used in this instrument to obtain high precision in the measurement of the intensity, degree of polarization, and orientation of the plane of polarization of light in the natural environment. The dual-channel configuration, with four interference filters in each channel, provides the possibility of measurements in eight narrow spectral intervals in the wavelength range 0.32-0.90 microm. Operation of the device, including rotation of the polarizing prism, selection of the filters, orientation in azimuth and elevation, and other mechanical processes, is controlled completely by a small electronic computer. The measurements are reduced to the physical quantities of interest on a real-time basis by the computer, which also is used to record the data on magnetic tape and print them out on a high speed printer as desired. Field operation has shown the instrument to be fast and reliable for measuring the intensity and polarization of sunlight, which may be of interest for characterizing atmospheric processes or the physical properties of natural surfaces.


Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds.
Objective: Chronic wounds are long-term nonhealing wounds that are refractory to treatment. These wounds can present elevated protease levels, leading to rapid degradation of native and exogenously added growth factors. This work focused on developing a protease-resistant growth factor formulation for treatment of chronic wounds presented with high protease activity. Approach: This study developed protease-resistant growth factor formulations comprising elastin-like peptides (ELPs) fused with a known protease inhibitor peptide or growth factor. The ELP component of the fusion proteins allows assembly of heterogeneous nanoparticles (NPs) putting the inhibitor in close proximity to the growth factor to be protected. Results: We show successful preservation of growth factor activity in high human neutrophil elastase (HNE) environment and in human chronic wound fluid derived from patients. We further show that these NPs result in enhanced collagen remodeling and resolution of inflammation in a full thickness wound supplemented with HNE in genetically diabetic mice. Innovation: Development of heterogeneous NPs that put the protease inhibitor in close proximity of the growth factor. Moreover, the modular nature of the NPs allows for protection of multiple growth factors by the same inhibitor without changing the amino acid sequence of the growth factor. Conclusion: Our results indicate that the developed NPs hold tremendous promise in chronic wound healing therapy and may further help the translation of growth factor therapies to clinic. The customizable template for the NP design allows for multifaceted use across several fields in research and medicine.


Assessment of physicians' perception of HIV+ patients' oral health.
The aim of this study was to design and validate an instrument for establishing perceptions of oral health held by physicians treating people living with HIV/AIDS. In order to design the instrument, four domains were identified that could measure the object of study and a 22-item questionnaire was created. The domains established were: knowledge of oral health; personal experience with oral health care; knowledge of oral health regarding HIV/AIDS; professional medical practices. To validate the instrument 50 physicians specializing in infectious diseases from public hospitals of Buenos Aires city completed the questionnaire using a Likert-type scale with 5 categories. The reliability of the instrument was assessed with the test and retest method at 30 days; internal consistency with Cronbach's alpha coefficient; content validity was determined by expert opinion; construct validity with the extreme groups method (Mann Whitney test, p < 0.05). All participants completed the test and retest questionnaires. Their mean age was 37.7 +/- 0.9 years; 36% were female and 64% male. The average experience in medical practice was 8.7 +/- 0.6 years. The instrument proved to be reliable as shown by the value of r(s) = 0.94 in the test-retest method; a satisfactory intra-item consistency was shown by Cronbach's alpha coefficient value of 0.91. The differences between the results of the groups of physicians in the extreme groups were statistically significant (p < 0.001). It is concluded that the instrument designed to measure the perception of oral health of physicians treating people living with HIV/AIDS is valid. However it would be desirable to enlarge the sample and determine criterion validity by comparison with other instruments.


Generation of an AraC-araBAD promoter-regulated T7 expression system.
An alternative and facile delivery system for T7 RNA polymerase has been devised and constructed. T7 gene 1 has been placed under control of the araBAD promoter element regulated by the AraC protein. Cotransformation of the resultant plasmid, pTara, with one containing a target gene under T7 promoter-regulated expression potentially allows repression by glucose and induction by arabinose in the range of 0.5 to 20 mM sugar concentration. To demonstrate the efficacy of this expression system, the p53 gene under T7 promoter control in two different plasmids was expressed in Escherichia coli using pTara as the source of T7 RNA polymerase. Repression and induction of p53 were achieved in both a lower and higher copy number plasmid, although the levels of induction were higher with the lower copy number expression vector. Cotransformation of an expression plasmid with pTara provides a low-cost method of T7 RNA polymerase-regulated expression that can be fine-tuned using glucose and arabinose concentrations to balance protein expression with potential solubility or toxicity problems.


A novel basis of capsid stabilization by antiviral compounds.
Picornaviruses are inactivated by a family of hydrophobic drugs that bind at an internal site in the viral capsid and inhibit viral uncoating. A basis for the capsid stabilization previously unrecognized is revealed by molecular dynamics simulations of the antiviral drug WIN52084s bound to a hydrophobic pocket of solvated human rhinovirus 14. Isothermal compressibilities of the complex and human rhinovirus 14 without the antiviral drug calculated from density fluctuations show that the presence of WIN52084s increases the compressibility of the viral capsid near the antiviral drug. This counterintuitive result is understandable on the basis of the empirical evidence of thermal melting temperatures and protein-folding entropies of globular proteins. Based on this evidence, we propose that a larger compressibility from drug binding confers greater thermal stability to capsid proteins by increasing the conformational entropy of capsids, thereby diminishing the entropy gain with uncoating. We suggest that compressibility is fundamental to the structural integrity of viral capsids and that examination of compressibility and antiviral activity will provide insights into the disassembly process.


Efficient reduction of nitrobenzene to aniline with a biocatalyzed cathode.
Nitrobenzene (NB) is a toxic compound that is often found as a pollutant in the environment. The present removal strategies suffer from high cost or slow conversion rate. Here, we investigated the conversion of NB to aniline (AN), a less toxic endproduct that can easily be mineralized, using a fed-batch bioelectrochemical system with microbially catalyzed cathode. When a voltage of 0.5 V was applied in the presence of glucose, 88.2 ± 0.60% of the supplied NB (0.5 mM) was transformed to AN within 24 h, which was 10.25 and 2.90 times higher than an abiotic cathode and open circuit controlled experiment, respectively. AN was the only product detected during bioelectrochemical reduction of NB (maximum efficiency 98.70 ± 0.87%), whereas in abiotic conditions nitrosobenzene was observed as intermediate of NB reduction to AN (decreased efficiency to 73.75 ± 3.2%). When glucose was replaced by NaHCO(3), the rate of NB degradation decreased about 10%, selective transformation of NB to AN was still achieved (98.93 ± 0.77%). Upon autoclaving the cathode electrode, nitrosobenzene was formed as an intermediate, leading to a decreased AN formation efficiency of 71.6%. Cyclic voltammetry highlighted higher peak currents as well as decreased overpotentials for NB reduction at the biocathode. 16S rRNA based analysis of the biofilm on the cathode indicated that the cathode was dominated by an Enterococcus species closely related to Enterococcus aquimarinus.


Analysis of Forecasting Indexes for Dental Caries in 3- to 6-year-old Children.
To analyse a possible predictive index for dental caries in 3 to 6 year old children in urban Beijing. Using random cluster sampling, 2,333 participants from six kindergartens, comprised of 35.7% 3-year-olds, 32.4% 4-year-olds and 31.9% 5-year-olds in urban Beijing were selected. At baseline, questionnaires were administered to about half of the parents. Children's oral health condition was examined at baseline and 6, 12 and 18 months later. In total there were 1,094 children who completed the 18-month evaluation. The baseline caries prevalence was 56.4%, and the mean dmft (decayed, missing and filled primary teeth) and dmfs (decayed, missing and filled primary surfaces) were 2.66 and 5.60, respectively. There were 62.3% parents who were aware of oral health knowledge, and amongst which the accuracy rate for attitudes regarding oral healthcare was 82.1%. The caries incidence in children who completed the evaluation was 55.3%, and mean increases in dmft and dmfs were 1.62 and 3.93, respectively. Predictive factors related to caries incidence were "past caries experience" [odds ratio (OR) = 4.969, P < 0.001], "parents help children brush teeth daily" (OR = 0.851, P = 0.046), and "parents consider that primary caries need to be treated" (OR = 1.270, P = 0.031). The sensitivity and specificity of "past caries experience" were 69.4% and 73.2%, respectively, and the sensitivity of the three indices combined was 88.4%. "Past caries experience" was an important predictor for primary caries incidence, and can be used in combination with "parents help children brush teeth daily" and "parents consider that primary caries need to be treated" as a predictive index.