Predicting Late Adolescent Anxiety From Early Adolescent Environmental Stress Exposure: Cognitive Control as Mediator.
Early exposure to stressful life events is associated with greater risk of chronic diseases and mental health problems, including anxiety. However, there is significant variation in how individuals respond to environmental adversity, perhaps due to individual differences in processing and regulating emotional information. Differences in cognitive control - processes necessary for implementing goal directed behavior - have been linked to both stress exposure and anxiety, but the directionality of these links is unclear. The present study investigated the longitudinal pathway of environmental stress exposure during early adolescence on later adolescent anxiety, and the possible mediating mechanism of cognitive control. Participants were 674 Mexican-origin adolescents (meanage = 10.8 years, 50% male) enrolled in the California Families Project, an ongoing longitudinal study of Mexican-origin families. In the current analysis, we examined self-reports of environmental stressors at age 14 (Time 1), cognitive control at age 16 (Time 2), and anxiety at age 18 (Time 3). Structural equation modeling revealed that environmental stressors (Time 1) had both direct and indirect effects on later anxiety (Time 3) through their effects on cognitive control (Time 2), even when accounting for prior levels of anxiety (Time 2). Cognitive control accounted for 18% of the association between environmental stressors and adolescent anxiety: an increase in stressors decreased cognitive control (β = -0.20, p < 0.001), however, cognitive control buffers against anxiety (β = -0.10, p = 0.004). These findings deepen our understanding of the mechanisms underlying the development of anxiety and highlight the importance of cognitive control as a potential protective factor.


Formation and elution of toxic compounds from sterilized medical products: methylenedianiline formation in polyurethane.
The formation of a toxic and carcinogenic compound, methylenedianiline (MDA), in sterilized medical use polyurethane (PU) is discussed. Due to good biocompatibility and biostability, PU is widely used for blood-containing devices. There are two types of PU currently available for medical use. One is chain-extended thermoplastic PU, the other is thermosetting PU used for potting material connecting fibers and modules in artificial dialyzers and plasma separators. Both gamma-ray irradiation and autoclave sterilization are predominantly used for the sterilization of these devices. MDA formation in sterilized PUs by gamma-ray irradiation and by autoclave treatment is compared. The Delany clause in the USA prohibits the manufacture of medical devices producing any toxic compound during fabrication and sterilization, therefore, the formation and elution of MDA and other toxic compounds should be seriously considered. Although MDA formation at a concentration of a few to a few hundred ppb in autoclaved chain-extended thermoplastic PU has been reported, there have been no papers describing MDA formation in autoclaved thermosetting PU potting material, or describing MDA formation in gamma-ray irradiated chain-extended thermoplastic PU and thermosetting PU. We elected to determine whether MDA was in fact produced in Pus sterilized by gamma-ray irradiation or by autoclave sterilization. Our objective was to estimate the risk factor to the human patients or recipient. Our conclusion is to confirm which sterilization of gamma-ray or autoclave is more appropriate. No formation of MDA was observed in autoclaved thermosetting PU potting material at 121 degrees C for 60 min. A few ppm of MDA was formed in irradiated potting material. MDA formation increased with increasing irradiation doses. MDA formed in irradiated potting material at 2.5 Mrad (less than one ppm) is not a significant risk to the recipient. The estimated cancer causing risk factor when absorbing one mg MDA/kg body weight/day is 0.29. Twenty-nine persons per 100 persons exhibit a cancer potential. More importantly, our experimental evidence indicated that serum extracts from irradiated potting material contained unknown compounds other than MDA. The presence of these compounds is considerably more significant and toxic. When tested, these compounds proved to be mutagenic in the absence of metabolic activity, thus promoting a need to identify and study further. Compounds indicating mutagenicity increased with increasing irradiation. Small amounts of mutagenic compounds were determined in extract from autoclaved potting material, smaller than that by gamma-ray irradiation. Therefore, autoclave sterilization is more appropriate, providing materials can withstand the process.(ABSTRACT TRUNCATED AT 400 WORDS)


Highly effective sulfated zirconia nanocatalysts grown out of colloidal silica at high temperature.
A large surface-to-volume ratio is a prerequisite for highly effective catalysts. Making catalysts in the form of nanoparticles provides a good way to achieve the aim. However, agglomeration of nanoparticles during the preparation and utilization of nanocatalysts remains a formidable problem. Here, we present a novel approach in which nano units of catalysts are formed in the matrix of a colloidal carrier, with assistance of a cross-linking agent, and then grow out of the carrier upon calcination at high temperature. This ensures that the catalysts not only do not agglomerate, but also have a low cost and high catalytic efficiency due to the large surface-to-volume ratio and the absence of carbon deposition. The technique is demonstrated by the successful preparation of a binary nanocatalyst that consists of a silica nanoparticle core and a sulfated zirconia (SZ) nanocrystal shell (JML-1). The synthesis was achieved by converting sulfated zirconia (SZ) and silica solutions into a composite gel by means of sol-gel processing in the presence of triethoxysilane as the cross-linking agent, followed by heating at 50 degrees C and calcining at 550 degrees C. Relative to other catalysts, such as pure SZ, non-nanodispersed SZ over silica (SZ/SiO2), and zeolites Y, Beta, and ZSM-5, JML-1 exhibits superior catalytic activity in many reactions. For example, the activity of JML-1 in the production of gasoline by alkylation of 1-butene with isobutene remained at 95% or higher after 20 h of reaction and was over 90% after being regenerated five times. In sharp contrast, SZ and SZ/SiO2 give a high activity only for 2 h and the initial activity of zeolites Beta and ZSM-5 are about 88 and 60%, respectively. These findings demonstrate that non-agglomerated nanoparticles anchored onto a carrier surface can be prepared and the technique provides a versatile route to new highly effective nanocatalyst systems.


MRSA infection in the neonatal intensive care unit.
Methicillin-resistant Staphylococcus aureus (MRSA) is well known as one of the most frequent etiological agents of healthcare-associated infections. The epidemiology of MRSA is evolving with emergence of community-associated MRSA, the clonal spread of some successful clones, their spillover into healthcare settings and acquisition of antibacterial drug resistances. Neonatal intensive care unit (NICU) patients are at an especially high risk of acquiring colonization and infection by MRSA. Epidemiology of MRSA in NICU can be very complex because outbreaks can overlap endemic circulation and make it difficult to trace transmission routes. Moreover, increasing prevalence of community-associated MRSA can jeopardize epidemiological investigation, screening and effectiveness of control policies. Surveillance, prevention and control strategies and clinical management have been widely studied and are still the subject of scientific debate. More data are needed to determine the most cost-effective approach to MRSA control in NICU in light of the local epidemiology.


Respiratory Viruses in Solid Organ Transplant Recipients.
Solid organ transplantation is often lifesaving, but does carry an increased risk of infection. Respiratory viral infections are one of the most prevalent infections, and are a cause of significant morbidity and mortality, especially among lung transplant recipients. There is also data to suggest an association with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. Respiratory viral infections can appear at any time post-transplant and are usually acquired in the community. All respiratory viral infections share similar clinical manifestations and are all currently diagnosed using nucleic acid testing. Influenza has good treatment options and prevention strategies, although these are hampered by resistance to neuraminidase inhibitors and lower vaccine immunogenicity in the transplant population. Other respiratory viruses, unfortunately, have limited treatments and preventive methods. This review summarizes the epidemiology, clinical manifestations, therapies and preventive measures for clinically significant RNA and DNA respiratory viruses, with the exception of SARS-CoV-2. This area is fast evolving and hopefully the coming decades will bring us new antivirals, immunologic treatments and vaccines.


Contrast enhancement in the phase plate transmission electron microscopy using an objective lens with a long focal length.
A new optical condition using an objective lens (OL) of a long focal length (objective mini lens: OM) was tested to enhance image contrast in phase plate transmission electron microscopy (P-TEM). A phase plate was set on the selected area aperture plane where diffraction patterns were formed under the optical condition using the OM. A phase shift by the phase plate was added to the electron waves to visualize phase objects. The application of the OM to the P-TEM should provide higher phase contrast than that obtained by the OL for the phase objects. One of the reasons for the contrast enhancement is that high-angle scattering electron waves which would give the background intensity were not used for image formation due to the large spherical aberration. Another reason is that the cut-on frequency above which the phase shift was added by the phase plate could be smaller using the OL with a long focal length. Experimental results and model calculations showed the contrast enhancement of the biological specimens using the OM.


Auto-immune gastritis induced by pembrolizumab, an anti-PD-1, in a melanoma patient.
We report a case of a 67-years-old woman presenting a severe acute lymphocytic gastritis induced by pembrolizumab, an immune check point inhibitor (ICI). This gastritis was her third auto-immune adverse event after 5 years of treatment with pembrolizumab, it was metabolically active at the PET Scan and confirmed by analysis of the gastric biopsies. Pembrolizumab treatment cessation and high doses of corticosteroids completely normalized the stomach clinically, endoscopically and histologically. This patient was in complete remission of her metastatic melanoma. Therefore, pembrolizumab therapy was not restarted and the patient is still in remission 6 months later. This strategy is supported by recent publications describing a relapse rate inferior to 10% in patients in complete remission after 2 years of immunotherapy. Particularities of this case are: rareness of this adverse event, late onset after introduction of pembrolizumab, evocative PET scan image, specific endoscopic aspect and histology. In addition, the favorable oncologic evolution of the patient after treatment cessation confirms the prolonged remission after immunotherapy.


Development, validation and transfer of a near infrared method to determine in-line the end point of a fluidised drying process for commercial production batches of an approved oral solid dose pharmaceutical product.
Pharmaceutical companies are progressively adopting and introducing the principles of Quality by Design with the main purpose of assurance and built-in quality throughout the whole manufacturing process. Within this framework, a Partial Least Square (PLS) model, based on Near Infrared (NIR) spectra and humidity determinations, was built in order to determine in-line the drying end point of a fluidized bed process. The in-process method was successfully validated following the principles described within The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use - ICH Q2 (r1) - Validation of Analytical Procedures: Text and Methodology. However, in some aspects, the cited guidelines were not appropriate to in-process methods developed and validated exclusively with in-line samples and implemented in dynamic systems, such as drying processes. In this work, a customized interpretation of guidelines has been adopted which provided the framework of evidence to support a validated application. The application has been submitted to the United States Food and Drug Administration (FDA) and The European Medicines Agency (EMA) during applications for grant of licences. Representatives from these Regulatory Authorities have specifically reviewed this novel application during on-site inspections, and have subsequently approved both the product and this application. Currently, the NIR method is implemented as a primary in-line method to control the drying end point in real-time (to below a control limit of not greater than 1.2% w/w) for commercial production batches of an approved, solid, oral-dose medicine. The implementation of this in-process method allows real-time control with benefits including a reduction in operation time and labour; sample handling and waste generation; and a reduced risk to product quality in further unit operations due to improved consistency of intermediate output at this stage. To date, this has achieved approximately 10% savings in energy efficiency and operational time for this part of the manufacturing process.


Genetic analysis of influenza A/H1N1 of swine origin virus (SOIV) circulating in Central and South America.
Since the first detection of swine origin virus (SOIV) on March 28, 2009, the virus has spread worldwide and oseltamivir-resistant strains have already been identified in the past months. Here, we show the phylogenetic analysis of 63 SOIV isolates from eight countries in Central and South America, and their sensitivity to oseltamivir.


Endometriosis mimicking glandular atypia in a cervical cytology.
Endometriosis involving the uterine cervix is a rare condition that can lead to diagnostic errors in the interpretation of Pap smear. We report the case of a 41-year-old patient in whom the initial Pap smear revealed three-dimensional clusters of glandular cells with elongated nuclei, occasional mitosis, and atypia, which was interpreted as atypical glandular cells, not otherwise specified (NOS). The patient was taken to colposcopy and endocervical biopsy. Colposcopy was normal and the biopsy presented glands with elongated nuclei and surrounded by endometrial stroma admixed with normal endocervical glands. Immunohistochemical studies were reactive for CD10 in the stromal cells and vimentin in endometrioid glands. The findings were consistent with cervical endometriosis. Endometriosis in the cervix is an uncommon pathology that mimics malignancy and may be interpreted as atypical or glandular neoplasia in the cytology.


The adaptive significance of unproductive alternative splicing in primates.
Alternative gene splicing is pervasive in metazoa, particularly in humans, where the majority of genes generate splice variant transcripts. Characterizing the biological significance of alternative transcripts is methodologically difficult since it is impractical to assess thousands of splice variants as to whether they actually encode proteins, whether these proteins are functional, or whether transcripts have a function independent of protein synthesis. Consequently, to elucidate the functional significance of splice variants and to investigate mechanisms underlying the fidelity of mRNA splicing, we used an indirect approach based on analyzing the evolutionary conservation of splice variants among species. Using DNA polymerase β as an indicator locus, we cloned and characterized the types and frequencies of transcripts generated in primary cell lines of five primate species. Overall, we found that in addition to the canonical DNA polymerase β transcript, there were 25 alternative transcripts generated, most containing premature terminating codons. We used a statistical method borrowed from community ecology to show that there is significant diversity and little conservation in alternative splicing patterns among species, despite high sequence similarity in the underlying genomic (exonic) sequences. However, the frequency of alternative splicing at this locus correlates well with life history parameters such as the maximal longevity of each species, indicating that the alternative splicing of unproductive splice variants may have adaptive significance, even if the specific RNA transcripts themselves have no function. These results demonstrate the validity of the phylogenetic conservation approach in elucidating the biological significance of alternative splicing.


Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes.
Meiosis I (MI), the division that generates haploids, is prone to errors that lead to aneuploidy in females. Haspin is a kinase that phosphorylates histone H3 on threonine 3, thereby recruiting Aurora kinase B (AURKB) and the chromosomal passenger complex (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an AURKB homolog, are enriched in germ cells, yet their significance in regulating MI is not fully understood. Using inhibitors and overexpression approaches, we show a role for haspin during MI in mouse oocytes. Haspin-perturbed oocytes display abnormalities in chromosome morphology and alignment, improper kinetochore-microtubule attachments at metaphase I and aneuploidy at metaphase II. Unlike in mitosis, kinetochore localization remained intact, whereas the distribution of the CPC along chromosomes was absent. The meiotic defects following haspin inhibition were similar to those observed in oocytes where AURKC was inhibited, suggesting that the correction of microtubule attachments during MI requires AURKC along chromosome arms rather than at kinetochores. Our data implicate haspin as a regulator of the CPC and chromosome segregation during MI, while highlighting important differences in how chromosome segregation is regulated between MI and mitosis.


MS specialist role deserves proper recognition from NICE, says charity.
A national charity has criticised the National Institute for Health and Care Excellence (NICE) for what it says is a failure to emphasise the importance of specialist nurses in updated guidance.


Removal of trace organic contaminants from domestic wastewater: A meta-analysis comparison of sewage treatment technologies.
Trace organic contaminants (TrOCs), such as endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs), represent global threats to aquatic animals and ecosystems. A major source of TrOCs in the aquatic environment is via the discharge of treated sewage, so there is an urgent need to evaluate the comparative efficiencies of the most widely used sewage treatment technologies as regards elimination of these compounds from wastewater. To address this need, 976 published articles were compiled focusing on estimates of removal (%) for 20 common environmental TrOCs, from five major sewage treatment technologies: conventional activated sludge (CAS), oxidation ditch (OD), membrane bioreactor (MBR), ponds and constructed wetlands (PCW), and trickling biological filters (TBF). A quantitative meta-analysis was performed to compare standardized relative removal efficiencies (SREs) of the compounds amongst these technologies, and where possible potential sources of heterogeneity were considered (e.g., flow rates and chemical sorption potential). The results indicate that the most widely used CAS treatment and the less common TBF provide comparatively poor overall removal of common organic micropollutants. Membrane bioreactors appear to be capable of achieving the greatest overall removal efficiencies, but the sustainability and economic viability of this option has been questioned. Treatment with OD systems may be more economical while still achieving comparatively high removal efficiencies, and the analysis revealed OD to be the best option for targeting highly potent estrogenic EDCs. This study offers a unique global assessment of TrOC removal via leading sewage treatment technologies, and is an important step in the identification of effective options for treating municipal sewage.


Noninvasive ventilation in pediatric intensive care.
The use of noninvasive ventilation (NIV) has become increasingly popular in the pediatric intensive care unit (PICU) over the last decade. This review intends to assess our current knowledge on the utilization of noninvasive support in children, especially focusing on its efficacy and safety profile. Recent studies endorse the use of this therapy in the pediatric intensive care setting. NIV appears to be associated with a decrease in the intubation rate in children. Children who are responsive to NIV will usually show improvement in their physiologic parameters shortly after the initiation of this therapy and this improvement is often sustained. NIV is proving to be a well-tolerated alternative to endotracheal intubation, in particular in those patients with primary respiratory failure, postsurgical patients or with postextubation respiratory distress. Most studies represent single-center experience and therefore caution must be exerted when attempting to generalize their results. NIV appears to be a well-tolerated alternative for use in the pediatric population. Its use is associated with decreased intubation rates, which may lead to a decrease in the intubation-related complications. More investigation is needed to fully evaluate the ramifications of increased use of this technology in the PICU.


Granulomatous interstitial nephritis associated with disseminated histoplasmosis in an immunocompetent patient.
We present a case of a 64-year-old man with a prolonged history of fatigue, weight loss, fever, and kidney failure. Kidney biopsy showed severe granulomatous interstitial nephritis with numerous giant cells. Silver stains identified fungal micro-organisms consistent with Histoplasma species. Despite antifungal treatment, the patient died of overwhelming infection a few weeks later. This report emphasizes the importance of diagnosing histoplasmosis early. A high degree of suspicion is required to make the diagnosis of histoplasmosis in a case of granulomatous interstitial nephritis.


Unusual posttraumatic porencephaly--case report.
An unusual case of posttraumatic porencephaly preceded by neither overt cerebral contusion nor hemorrhage is reported. The cerebral cortex just above the porencephalic cyst was found intra-operatively to be partially herniated into a fracture line, while the cortex elsewhere was completely intact. The porencephalic cyst communicated with the lateral ventricle. Apparently, brain herniation and the cyst-ventricle communication can be causative factors in the occurrence and growth of posttraumatic porencephaly.


Fine needle aspiration biopsy-RT-PCR molecular analysis of thyroid nodules: a useful preoperative diagnostic tool.
Fine needle aspiration biopsy (FNAB)-based cytology is an accurate preoperative diagnostic method for the evaluation of thyroid nodules. Despite its high specificity and sensitivity, the results are non-diagnostic in a significant number of cases, commonly due to inadequacy of the samples or the presence of undetermined cellular morphology. Overlap-ping cytologic features among follicular-derived lesions are the most common causes of cyto-histopathologic discordances. The management of thyroid nodules with a non-diagnostic FNAB remains controversial. The significant probability of malignancy imposes either the repeat of the procedure or direct surgery. Recent studies have demonstrated the important role of molecular-based techniques such as RT-PCR in the diagnosis of thyroid lesions. Follicular cells obtained from the remaining material within the needle can be used for RNA extraction and then for RT-PCR amplification of specific mRNAs that are expressed in benign or malignant thyroid nodules. Furthermore, FNAB-RT-PCR in combination with molecular scanning techniques or direct sequencing provides a valuable screening tool for mutations. The present review highlights the applications of FNAB-RT-PCR method in the identification of new diagnostic molecular markers. The parallel molecular and cytological analysis of FNABs may contribute to a more accurate diagnosis and, thus, to a more specific clinical management of thyroid nodules.


What do patients learn about psychotropic medications on the web? A natural language processing study.
Low rates of medication adherence remain a major challenge across psychiatry. In part, this likely reflects patient concerns about safety and adverse effects, accurate or otherwise. We therefore sought to characterize online information about common psychiatric medications in terms of positive and negative sentiment. We applied a natural language processing tool to score the sentiment expressed in web search results for 51 psychotropic medications across 3 drug classes (antidepressants, antipsychotics, and mood stabilizers), as a means of seeing if articles referencing these medications were generally positive or generally negative in tone. We compared between medications of the same class, and across medication classes. Across 12,733 web search results, significant within-class differences in positive (antidepressants: F(24,2682) = 2.97, p < 0.001; antipsychotics: F(16,4029) = 3.25, p < 0.001; mood stabilizers: F(8,2371) = 6.88, p < 0.001) and negative sentiment (antidepressants: F(24,6282) = 11.17, p < 0.001; antipsychotics: F(16, 4029) = 12.13, p < 0.001; mood stabilizers: F(8, 2371) = 13.28, p < 0.001) were identified. Among these were significantly greater negative sentiment for the antidepressants sertraline, duloxetine, venlafaxine, and paroxetine, and for the antipsychotics, quetiapine and risperidone. Conversely, lithium preparations and valproate exhibited less negative sentiment than other mood stabilizing medications. While these results provide a novel means of comparing medications, the present analyses cannot be linked to individual patient consumption of this information, or to its influence on their future clinical interactions. Overall, a subset of psychotropic medications were associated with significantly more negative sentiment. Characterizing these differences may allow clinicians to anticipate patient willingness to initiate or continue medications.


The feasibility of superparamagnetic iron oxide-enhanced magnetic resonance imaging for assessing liver lesions in patients with contraindications for iodine CT contrast media or gadolinium-based MR contrast media: a retrospective case-control study.
The detection and characterization of liver lesions are problematic in patients with bronchial asthma, renal dysfunction, or a history of allergy to gadolinium-based magnetic resonance contrast media or iodine-computed tomography contrast media because these contrast media cannot be used. Hence, the information on the lesion vascularity cannot be obtained. Therefore, this retrospective case-control study evaluated the feasibility of superparamagnetic iron oxide (SPIO) in patients with one or more of these contraindications who underwent SPIO-enhanced magnetic resonance imaging for the assessment of liver lesions. Twenty-six patients with a total of 48 lesions were analyzed. SPIO was used in the case of all patients because each patient had at least one reason not to use iodine contrast or gadolinium-based contrast media. Additionally, all patients were subjected to the perfusion study. A total volume of 1.3 mL of SPIO was injected via the cubital vein at a rate of 3 mL per second, followed by 40 mL saline at the same speed. The scanning of the perfusion study was started 4 s after the beginning of superparamagnetic iron oxide injection and scanning took 50 s. Two radiologists independently evaluated whether the lesion was malignant or benign. Receiver operating characteristic analysis (ROC) was performed to determine the additional benefit of the perfusion study. There were no adverse effects associated with SPIO. The area under the curve (AUC) value without perfusion study for observers 1 and 2 were 0.473 (P=0.794, 95% CI: 0.275-0.672) and 0.602 (P=0.305, 95% CI: 0.407-0.798), respectively, whereas the Az values with perfusion study for observers 1 and 2 were 0.782 (P=0.011, 95% CI: 0.565-0.998) and 0.784 (P=0.004, 95% CI: 0.591-0.977), respectively. Az value became significantly better when the perfusion study has added (P=0.001 and 0.012 by observers 1 and 2). SPIO can be used safely in patients with bronchial asthma, renal dysfunction, or a history of contrast media allergy. Furthermore, the diagnostic accuracy of SPIO was acceptable.


A systematic review of premorbid cognitive functioning and its timing of onset in schizophrenia spectrum disorders.
Cognitive impairments are core features of established schizophrenia spectrum disorders (SSD). However, it remains unclear whether specific cognitive functions are differentially impaired pre-onset and at what age these impairments can be detected. The purpose of this review was to elucidate these issues through a systematic summary of results from longitudinal studies investigating impairment in specific cognitive domains as antecedents of SSD. Relevant studies were identified by electronic and manual literature searches and included any original study of cognitive domains any time pre-onset of SSDs that included a control group. Effect sizes were calculated by domain for studies comparing high-risk participants who developed SSD with those who did not. The strongest evidence for impairment pre-onset was for mental processing speed, verbal learning and memory, executive function, and social cognition. Some verbal impairments, like language abilities at age 3 and verbal learning and memory at age 7, may develop as static deficits. Conversely, some non-verbal impairments, like mental processing speed, visuospatial abilities, and visual working memory manifest as developmental lag and become significant later in life. Most effect sizes were small to moderate, except for verbal fluency (d' = 0,85), implying this impairment as central in high-risk participants who develop SSD. The present review documents extensive cognitive impairments pre-onset of SSD, and that these impairments start early in life, in line with the neurodevelopmental hypothesis of schizophrenia. Increased knowledge about cognitive impairments preonset can provide a better basis for understanding the complex pathogenesis of SSD as well as informing cognitive remediation programs.


Management of staphylococcal endocarditis in drug addicts. Combined therapy with oral rifampicin and aminoglycosides.
Staphylococcal endocarditis is a condition affecting intravenous drug abusers at increasing rates, and its treatment is still controversial. We used, successfully, high doses of rifampicin, associated with an aminoglycoside, for the treatment of two heroin addicts. In the first we found a left-sided endocarditis with metastatic abscesses in brain, both kidneys, liver and spleen; in the other the finding of bilateral lung abscesses was related to embolic episodes from a diseased tricuspid valve. Since the isolated strains of Staphylococcus aureus were tolerant to methicillin, we used oral rifampicin (20 mg/kg/day) plus an aminoglycoside (amikacin in the former and gentamicin in the latter), after in-vitro testing had proved these combinations to be effective. We achieved, in both cases stable bactericidal concentrations in the serum and a lasting clinical recovery.


[Alcohol tolerance in patients with non-insulin-dependent diabetes (type 2) treated orally with drugs--derivatives of sulphonylurea].
The oral ethanol loading test (0.5 g per kg b.m. given as 40% solution) was carried out in 5 groups, each of 10 patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide 0.5 t.i.d., chlorpropamide 0.5 once daily morning, glibornuride 0.025 t.i.d, glibenclamide 0.005 t.i.d. and glipizide 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentration of ethanol, acetaldehyde, pyruvate, lactate, carbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism. All studied drugs intensified to a similar degree the alcohol-induced hypoglycaemia, but had no significant effect on the decrease of blood pyruvate level neither on the increase of blood lactate level. They didn't change the post-alcohol decrease of blood bicarbonate and pH, and didn't modify the behaviour of partial gas pressure. There was also no difference between pooled groups of patients with positive and negative thermographic reaction with respect to family history of diabetes and frequency and intensity of vascular complications. It is concluded that in patients with non-insulin-dependent (type 2) diabetes the second generation sulphonylurea derivatives are associated with lower risk of alcohol intolerance in case of its incidental ingestion in small amounts. The hypothesis of association of positive thermographic reaction to alcohol during treatment with sulphonylurea derivatives with more frequent occurrence of diabetes in family members and lower tendency to vascular complications was not confirmed.


Uncoupled changes in the expression of the jun family members during myeloid cell differentiation.
The differentiation into macrophages of the U937 and HL60 human cell lines induced by 4 beta-phorbol 12-myristate 13-acetate (PMA) was accompanied by induction of the expression of the proto-oncogenes c-jun, jun B and jun D. However, expression of the three jun genes was regulated differently during induction of cell differentiation in both U937 and HL60 cells, with the three jun family members being expressed distinctly at different stages of cell differentiation. Whereas jun B transcription was strongly stimulated following treatment with PMA for 30 min, jun D mRNA levels were only increased 6 h after PMA treatment and the content of c-jun mRNA was elevated maximally only 24 h after PMA treatment. The rapid induction of the jun B mRNA level suggests a putative role for this proto-oncogene in the early triggering step of U937 and HL60 cell differentiation induced by PMA. Interestingly, a weak induction of jun B and jun D mRNA levels, but no induction of the c-jun mRNA level, was detected during Me2SO-induced granulocytic HL60 differentiation. These data suggest a different role for each jun proto-oncogene in regulating gene activity and that different transcriptional complexes involving distinct jun proto-oncogenes can be formed during macrophage and granulocytic differentiation.


Allelic depletion of grem1 attenuates diabetic kidney disease.
Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy. Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes. A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1(+/-) mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1(+/-) and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1(+/-) mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1. These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.


Involvement of G protein-coupled receptor kinase 5 in homologous desensitization of the thyrotropin receptor.
Homologous desensitization of G protein-coupled receptors involves agonist-dependent phosphorylation of receptors by G protein-coupled receptor kinases (GRKs). To identify GRK(s) that play a role in homologous desensitization of the thyrotropin (TSH) receptor, thyroid cDNA was amplified by polymerase chain reaction using degenerate oligonucleotide primers from highly conserved regions in GRK family. GRK5 is found in the predominant isoform expressed in the thyroid. Rat GRK5 cDNA was then isolated, which encodes a 590-amino acid protein with 95% homology to human and bovine homologs. Northern blot identified GRK5 mRNA of approximately 3, 8, and 10 kilobases with highest expression levels in lung > heart, kidney, colon > thyroid. In functional studies using a normal rat thyroid FRTL5 cells, overexpression of GRK5 by transfecting the plasmid capable of expressing the sense GRK5 RNA suppressed basal cAMP levels and augmented the extent of TSH receptor desensitization, whereas suppression of endogenous GRK5 expression by transfecting the antisense GRK5 construct increased basal cAMP levels and attenuated the extent of receptor desensitization. Although exogenously overexpressed GRK6 also enhanced TSH receptor desensitization, we conclude that GRK5, the predominant GRK isoform in the thyroid, appears to be mainly involved in homologous desensitization of the TSH receptor.


Risk assessment of environmentally influenced airway diseases based on time-series analysis.
Threshold values are of prime importance in providing a sound basis for public health decisions. A key issue is determining threshold or maximum exposure values for pollutants and assessing their potential health risks. Environmental epidemiology could be instrumental in assessing these levels, especially since the assessment of ambient exposures involves relatively low concentrations of pollutants. This paper presents a statistical method that allows the determination of threshold values as well as the assessment of the associated risk using a retrospective, longitudinal study design with a prospective follow-up. Morbidity data were analyzed using the Fourier method, a time-series analysis that is based on the assumption of a high temporal resolution of the data. This method eliminates time-dependent responses like temporal inhomogeneity and pseudocorrelation. The frequency of calls for respiratory distress conditions to the regional Mobile Medical Emergency Service (MMES) in the city of Leipzig were investigated. The entire population of Leipzig served as a pool for data collection. In addition to the collection of morbidity data, air pollution measurements were taken every 30 min for the entire study period using sulfur dioxide as the regional indicator variable. This approach allowed the calculation of a dose-response curve for respiratory diseases and air pollution indices in children and adults. Significantly higher morbidities were observed above a 24-hr mean value of 0.6 mg SO2/m3 air for children and 0.8 mg SO2/m3 for adults.(ABSTRACT TRUNCATED AT 250 WORDS)


Report of the Stigma Research Workshop for the development of scientific consensus papers and field guidelines on health-related stigma, held in Amsterdam, the Netherlands from 11-14 october 2010.
Summary In concurrence with the broad body of literature published on health-related stigma, there is a need for practical field guidance to contribute to the fight against leprosy-related stigma and discrimination. To this end, much can be gained by considering the accumulated knowledge and learned from experience with different stigmatising conditions; primarily HIV/AIDS, disability, tuberculosis, and mental health. Therefore a Stigma Research Workshop was organised from 11-14 October in Amsterdam, The Netherlands. The primary aim of the workshop was to produce scientific papers and field guidelines that could be used to target actions against health-related stigma and discrimination. Keynote presentations were offered by scientists and professionals from different health domains who shared their knowledge, experiences and research findings regarding health-related stigma. Group work was subsequently conducted to work towards agreed outputs on four different themes: i.e. research priorities, measurement, interventions, and counselling. The spectrum of expertise present enabled an interdisciplinary and inter-profession sharing of knowledge and practices. This resulted in the commencement of consensus papers and field guidelines related to the four themes. An evaluation by participants concluded that the workshop had been an informative and worthwhile activity that will strengthen the fight against stigma.


Stretchable piezoelectric nanocomposite generator.
Piezoelectric energy conversion that generate electric energy from ambient mechanical and vibrational movements is promising energy harvesting technology because it can use more accessible energy resources than other renewable natural energy. In particular, flexible and stretchable piezoelectric energy harvesters which can harvest the tiny biomechanical motions inside human body into electricity properly facilitate not only the self-powered energy system for flexible and wearable electronics but also sensitive piezoelectric sensors for motion detectors and in vivo diagnosis kits. Since the piezoelectric ZnO nanowires (NWs)-based energy harvesters (nanogenerators) were proposed in 2006, many researchers have attempted the nanogenerator by using the various fabrication process such as nanowire growth, electrospinning, and transfer techniques with piezoelectric materials including polyvinylidene fluoride (PVDF) polymer and perovskite ceramics. In 2012, the composite-based nanogenerators were developed using simple, low-cost, and scalable methods to overcome the significant issues with previously-reported energy harvester, such as insufficient output performance and size limitation. This review paper provides a brief overview of flexible and stretchable piezoelectric nanocomposite generator for realizing the self-powered energy system with development history, power performance, and applications.


Synthesis, molecular docking and ADME studies of thiazole-thiazolidinedione hybrids as antimicrobial agents.
New thiazole-thiazolidinedione hybrids (5a-k) were efficiently synthesized and evaluated for their in-vitro antimicrobial activity against four fungal and bacterial strains. The chemical structures of the compounds were elucidated by FTIR, 1H NMR, and 13C NMR spectral data. Most of the synthesized compounds were sensitive against gram positive, gram negative bacterial and fungal strains. Among the synthesized molecules, compounds 5h, and 5i exhibited promising inhibitory activity against all selected fungal strains and gram positive bacteria namely, Staphylococcus aureus, and Enterococcus faecalis. The molecular docking results predicted that the thiazole-thiazolidinedione derivatives bind to the active site protein ATP-binding pocket from E. coli, S. aureus and C. albicans with good interaction energy scores. Ct-DNA was used to evaluate the binding interactions of the selected compounds by means of absorption spectroscopy. To further characterize the drug-likeness and ADME properties were calculated using the Qikprop, the result of present study suggests that thiazole-thiazolidinedione hybrid could be an interesting approach for the design of new antimicrobial agents.Communicated by Ramaswamy H. Sarma.


Fluid as a Drug: Balancing Resuscitation and Fluid Overload in the Intensive Care Setting.
Intravenous fluid resuscitation is ubiquitous throughout medicine and is often considered a benign procedure. Yet, there is now clear recognition of the potential harms of fluid overload after initial resuscitation. In recent years, there has also been an increasing focus on comparing various resuscitation fluids with respect to both benefits and risks. Studies have examined colloids, such as albumin and starches, against the clinical standard of crystalloids. In addition, evidence has emerged to suggest that outcomes may be different between resuscitation with chloride-rich vs balanced crystalloid solutions. In this article, we review the current literature regarding choice of intravenous fluids for resuscitation in the intensive care setting and describe the dangers associated with fluid overload in critically ill patients.


Treatment of Tannery Effluent Using a Rotating Disc Electrochemical Reactor.
A novel rotating disc electrochemical (RDE) reactor has been developed to treat tannery effluent. Experiments were carried out in batch, batch recirculation, and once-through modes in the reactor covering wide range of operating conditions. The effect of current density (i), cathode rotation speed (R), electrolysis time (t), influent pH, and electrolyte flow rate (Q) on the pollutant removal efficiency and specific energy consumption was critically evaluated. The response of the process parameters were measured in terms of percentage total organic carbon (TOC) removal. The reaction mechanism of electro-oxidation was modeled using first-order kinetics. GC-MS and FT-IR analysis of the raw and treated effluent show that the tannery effluent can be effectively treated using the RDE reactor.


A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma.
Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model for evaluating the risk of LUAD based on hypoxia, immunity, and epithelial-mesenchymal transition (EMT) gene signatures. Methods: In this study, we used data from TCGA-LUAD for the training cohort and GSE68465 and GSE72094 for the validation cohorts. Immunotherapy datasets GSE135222, GSE126044, and IMvigor210 were obtained from a previous study. Using bioinformatic and machine algorithms, we established a risk model based on hypoxia, immune, and EMT gene signatures, which was then used to divide patients into the high and low risk groups. We analyzed differences in enriched pathways between the two groups, following which we investigated whether the risk score was correlated with stemness scores, genes related to m6A, m5C, m1A and m7G modification, the immune microenvironment, immunotherapy response, and multiple anti-cancer drug sensitivity. Results: Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26). The AUCs for predicting 1-, 3-, and 5-year survival were 0.763, 0.766, and 0.728, respectively. In the GSE68465 dataset, the HR was 2.03, while the AUCs for predicting 1-, 3-, and 5-year survival were 0.69, 0.651, and 0.618, respectively. The corresponding values in the GSE72094 dataset were an HR of 2.36 and AUCs of 0.653, 0.662, and 0.749, respectively. The risk score model could independently predict OS in patients with LUAD, and highly correlated with stemness scores and numerous m6A, m5C, m1A and m7G modification-related genes. Furthermore, the risk model was significantly correlated with multiple immune microenvironment characteristics. In the GSE135222 dataset, the HR was 4.26 and the AUC was 0.702. Evaluation of the GSE126044 and IMvigor210 cohorts indicated that PD-1/PD-LI inhibitor treatment may be indicated in patients with low risk scores, while anti-cancer therapy with various drugs may be indicated in patients with high risk scores. Conclusion: Our novel risk model developed based on hypoxia, immune, and EMT gene signatures can aid in predicting clinical prognosis and guiding treatment in patients with LUAD.


Differences in nutrient intakes and physical activity levels of Japanese and Australian Caucasian males living in Australia and Japanese males living in Japan.
The aim of the study was to determine the nutritional status and nutrient intakes of young Japanese males living in Australia and compared with Japanese males living in Japan and Australian Caucasian males. Four-day dietary records were obtained from 65 Japanese living in Australia (JA), 81 Japanese living in Japan (JJ), and 70 Australian Caucasian males (AA) aged 18-30 years old, together with body composition and physical activity level assessments using anthropometry and the questionnaire. Australian males were significantly taller and heavier than the Japanese counterparts and also showed a greater percent body fat (%BF) and height-corrected sum of skinfolds compared with Japanese males living in Japan (%BF: JJ = 16.6 +/- 5.2, AA = 18.7 +/- 5.6; height corrected sum of skinfolds: JJ = 78.8 +/- 37.3, AA = 96.0 +/- 39.5) (P<0.05). A greater proportion of Australian Caucasian males (98.6%) were involved in vigorous physical exercise than Japanese males (JA = 72.3%; JJ = 85.2%). The JA group consumed a greater amount of energy from protein and fat sources as well as greater calcium, iron, dietary fibre and niacin equivalents intakes than the JJ group (P<0.05). The results suggest that Japanese males living in Australia consumed more energy-dense westernised diet than Japanese males living in Japan. Because of lower physical activity level than Australian males, consumption of energy-dense diet may increase the risk of weight gain among Japanese males who stay in Australia for a long-term.


Growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of Lactobacillus upon ultraviolet radiation.
The objective of this study was to evaluate the effects of ultraviolet (UV) radiation (UVB; 90 J/m²) on growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of L. casei FTDC 2113. UV radiation significantly enhanced (P < 0.05) the growth of parent cells in mannitol-soymilk fermented at 37°C for 24 h. This had led to an enhanced intracellular and extracellular β-glucosidase activity with a subsequent increase in bioconversion of isoflavones in mannitol-soymilk (P < 0.05). UV radiation also promoted (P < 0.05) the tolerance of parent cells towards acidic condition (pH 2 and 3) and intestinal bile salts (oxgall, taurocholic and cholic acid). In addition, parent treated cells also exhibited better (P < 0.05) adhesion ability to mucin and antimicrobial activity compared to that of the control. All these positive effects of UV radiation were only prevalent in the parent cells without inheritance by first, second and third passage of cells. Although temporary, our results suggested that UV radiation could enhance the bioactive and probiotic potentials of L. casei FTDC 2113, and thus could be applied for the production of probiotic products with enhanced bioactivity.


Variation in Neonatal Inpatient Charges at the State and Local Level.
In an analysis of all Ohio newborn infants discharged home alive between 2007 and 2012, the authors identified that significant variation in hospital charges (among Medicare Severity Diagnostic Related Group categorizations), previously identified nationally, persists at the state and local levels among term and preterm infants (p <.0001). Additionally, the authors identified variation in length of stay among infants with extreme immaturity or respiratory distress syndrome (p <.0001). Charge data remain the best available proxy for closely guarded hospital cost figures; increased pricing transparency would further support comparison of hospital newborn care costs.


SRPX2 promotes cell migration and invasion via FAK dependent pathway in pancreatic cancer.
Sushi repeat-containing protein, X-linked 2, abbreviated as SRPX2, is a candidate downstream target protein for E2A-HLF and involved in disorders of language cortex and cognition. Recent studies have demonstrated that elevated SRPX2 exhibits crucial roles in gastric cancer, however, underlying clinical significance and biological function of SRPX2 in pancreatic ductal adenocarcinoma (PDAC), remains unclear. Data from Oncomine database showed that higher SRPX2 expression is more commonly observed in PDAC compared with normal pancreatic duct, similar results were also found in 12 matched PDAC tissue samples, 7 PDAC cell lines and a tissue microarray containing 81 PDAC specimens as demonstrated by real-time quantitative PCR and immunohistochemistry, respectively. Besides, higher SRPX2 expression was closely correlated with advanced TNM stage. Silencing of endogenous SRPX2 expression reduced abilities of cell migration and invasion of PDAC cells. Further studies revealed that SRPX2 expression in PDAC tissues significantly correlated with the phosphorylation levels of FAK, indicating that FAK dependent pathway may be account for the effect of SRPX2 on cell migration and invasion in PDAC. Collectively, this study reveals that frequently elevated SRPX2 contributes to cell migration and invasion in PDAC and SRPX2-related pathways might be a potential therapeutic target for PDAC.


Influence of tedisamil on the initiation and maintenance of ventricular fibrillation: chemical defibrillation by Ito blockade?
We examined the effects of tedisamil on ventricular fibrillation (VF) elicited by regional ischemia and by reperfusion in isolated rat hearts (n = 12/group). During 30 min of ischemia, 0.1, 0.55, and 3 microM tedisamil had no influence on the incidence of VF (an index of VF initiation). However, sustained VF (SVF, defined as that lasting greater than 120 s, an index of VF maintenance) was reduced in a concentration-dependent manner from 73 to 54, 17 (p less than 0.05), and 0% (p less than 0.05), respectively. Tedisamil caused sinus bradycardia but this was not the basis for tedisamil's antiarrhythmic activity since SVF was also inhibited in separate groups of hearts that were paced throughout the study. Tedisamil had no effect on reperfusion-induced VF initiation. However, VF maintenance was, again, inhibited, with SVF incidence reduced from 75% to 40, 20, and 0% (p less than 0.05), respectively, by increasing concentrations of tedisamil. A similar effect was, again, observed in paced hearts. The average cycle length of the electrogram during VF correlated with preceding width of the ventricular complex; both of these variables were concentration-dependently increased by tedisamil and mean values of each correlated inversely with the incidence of SVF. The ratio of SVF cycle length to ventricular tachycardia cycle length was 1:3, and this ratio was conserved in the presence and absence of drug. The data are consistent with a drug-induced increase in the probability of spontaneous termination of multiple wave-front re-entry.


Sugar digestion efficiencies of Gurney's sugarbirds, malachite sunbirds, and black sunbirds.
This study determined the interaction between energy assimilation and digestive constraints on the foraging behaviour of nectarivorous Gurney's sugarbirds (Promerops gurneyi), black sunbirds (Nectarinia amethystina), and malachite sunbirds (Nectarinia famosa) in the laboratory. Rates of sugar intake and consumption, transit time, and the concentration of sugar in the excreta were measured when birds were fed 0.25 mol L-1 sucrose, 0.73 mol L-1 sucrose, and 0.73 mol L-1 glucose. For each species, intake rates by volume were greater at low sugar concentrations, such that energy intakes per 90 min were similar, irrespective of diet, which supports the idea of regulated energy intake for these nectarivorous birds. All species were efficient at energy extraction, excreting 1% or less sucrose equivalent irrespective of the initial sugar concentration of each diet. Transit times of solutions ingested increased with an increase in sugar concentration. Birds maximized energy assimilation on high- and low-energy nectar diets by having high extraction efficiencies and short transit times. Sugarbird and sunbird foraging behaviours may be limited by digestive processes and the cost of carrying high-energy reserves as nectar sugar concentration increases.


Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats.
Chronic inflammation is an important risk factor in a broad variety of physical and mental disorders leading to highly prevalent non-communicable diseases (NCDs). However, there is a need for a deeper understanding of this condition and its progression to the disease state. For this reason, it is important to define metabolic pathways and complementary biomarkers associated with homeostatic disruption in chronic inflammation. To achieve that, male Wistar rats were subjected to intraperitoneal and intermittent injections with saline solution or increasing lipopolysaccharide (LPS) concentrations (0.5, 5 and 7.5 mg/kg) thrice a week for 31 days. Biochemical and inflammatory parameters were measured at the end of the study. To assess the omics profile, GC-qTOF and UHPLC-qTOF were performed to evaluate plasma metabolome; 1H-NMR was used to evaluate urine metabolome; additionally, shotgun metagenomics sequencing was carried out to characterize the cecum microbiome. The chronicity of inflammation in the study was evaluated by the monitoring of monocyte chemoattractant protein-1 (MCP-1) during the different weeks of the experimental process. At the end of the study, together with the increased levels of MCP-1, levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) along with 8-isoprostanes (an indicative of oxidative stress) were significantly increased (p-value < 0.05). The leading features implicated in the current model were tricarboxylic acid (TCA) cycle intermediates (i.e., alpha-ketoglutarate, aconitic acid, malic acid, fumaric acid and succinic acid); lipids such as specific cholesterol esters (ChoEs), lysophospholipids (LPCs) and phosphatidylcholines (PCs); and glycine, as well as N, N-dimethylglycine, which are related to one-carbon (1C) metabolism. These metabolites point towards mitochondrial metabolism through TCA cycle, β-oxidation of fatty acids and 1C metabolism as interconnected pathways that could reveal the metabolic effects of chronic inflammation induced by LPS administration. These results provide deeper knowledge concerning the impact of chronic inflammation on the disruption of metabolic homeostasis.


Atonal homolog 8/Math6 regulates differentiation and maintenance of skeletal muscle.
Atonal Homolog 8 (Atoh8) belongs to a large superfamily of transcriptional regulators called basic helix-loop-helix (bHLH) transcription factors. Atoh8 (murine homolog "Math6") has been shown to be involved in organogenesis during murine embryonic development. We have previously identified the expression of Atoh8 during skeletal myogenesis in chicken where we described its involvement in hypaxial myotome formation suggesting a regulatory role of Atoh8 in skeletal muscle development. Within the current study, we analyzed the effect of the loss of function of Atoh8 in murine primary myoblasts and during differentiation of pluripotent stem cells into myotubes, and the effect of its gain of function in C2C12 cells. Based on the observed results, we conclude that Atoh8 regulates myoblast proliferation via modulating myostatin signaling. Further, our data revealed a reduced muscle mass, strength and fiber size with significant changes to the muscle fiber type suggesting atrophy in skeletal muscle of Atoh8 mutants. We further report that Atoh8 knockout mice suffer from a condition similar to ambient hypoxia which may be the primary cause of the phenotype. Altogether, this study shows the significance of Atoh8 not only in myogenesis but also in the maintenance of skeletal muscle.


Ammonia regulation of carbon metabolism in photosynthesizing leaf discs.
Alfalfa (Medicago sativa L., var. El Unico) leaf discs, floating on buffer containing NH(4)Cl and photosynthesizing with (14)CO(2), produced more labeled amino acid and less sucrose than did control discs (no added NH(4)Cl). The level of pyruvate increased and that of phosphoenolpyruvate decreased. These and other changes in levels of labeled compounds led us to conclude that pyruvate kinase was activated by ammonia, resulting in increased transfer of photosynthetically incorporated carbon to synthesis of amino acid skeletons at the expense of sucrose synthesis. Carbon flow through enzymes catalyzing the anaplerotic reactions was apparently stimulated.


Social Skills in Children Adopted from Socially-Emotionally Depriving Institutions.
This study assessed social skills in post-institutionalized (PI) children with respect to age-at-adoption, age-at-assessment, and gender. Parent ratings of social skills (Social Skills Rating System) and behavior problems (Child Behavior Checklist) were obtained for 214 children and 127 adolescents who were adopted from socially-emotionally depriving Russian institutions. Results showed that children adopted before 18 months of age have better social skills than those adopted after this age; those assessed in childhood demonstrate better social skills than those assessed in adolescence. PI females, especially later-adopted adolescents, have particularly poor social skills. Children with poor social skills tend to have higher rates of behavior problems.


Egg quality assurance programs and egg-associated Salmonella enteritidis infections, United States.
A Salmonella enterica serovar Enteritidis epidemic in the United States began in 1978, spread to much of the country in the following decade, and began declining in 1996. We examined correlations between annual changes in S. Enteritidis incidence in humans and introductions of egg quality assurance programs (EQAPs) in some states to reduce S. Enteritidis contamination of eggs. Before EQAPs, 62% of the changes in S. Enteritidis incidence were higher than the baseline for each state. After EQAPs, 73%-84% of the changes were below the baseline. Regression analysis showed that a 1% increase in the number of eggs produced under an EQAP was associated with a 0.14% decrease in S. Enteritidis incidence (p < 0.05). These data indicate that EQAPs probably played a major role in reducing S. Enteritidis illness in these states.


Resistance Exercise for Breast Cancer Patients? Evidence from the Last Decade.
Breast cancer is associated with many therapy-induced side effects that impact patients' lives from diagnosis to long-term survivorship. Physical activity has become an important and proven supportive measure in treating side effects like loss of muscle strength, fatigue, chemotherapy-induced peripheral neuropathy, lymphedema, and loss of quality of life. Resistance training (RT) is an established exercise intervention for breast cancer patients, but the correct type, timing, intensity, and duration of exercise remain unclear. It is necessary to investigate different resistance training interventions and their effects on breast cancer patients by covering all stages of treatment, beginning with prehabilitation, through the period of acute therapy, to long-term survivorship. Upon evaluation of randomized controlled trials (RCTs) from the past decade, RT was found to be feasible and safe. Furthermore, there is evidence on the impact of RT on muscle strength, CRF and QoL amongst other factors. Studies implementing mixes of aerobic and strength exercises are rather common, but RCTs of RT-only protocols remain scarce. Different strength training protocols at distinct stages of breast cancer treatment have been conducted, but with the complexity of treatments and the variety of training styles, a large field of study remains. Although the overall data on RT for breast cancer patients has increased, there are many different methodological approaches and testing measures as well as gaps in study documentation. There is still very little of the evidence that would facilitate the compilation of standardized and individualized guidelines.


iso-DGR sequences do not mediate binding of fibronectin N-terminal modules to adherent fibronectin-null fibroblasts.
Fibronectin (FN) without an RGD sequence (FN-RGE), and thus lacking the principal binding site for alpha5beta1 integrin, is deposited into the extracellular matrix of mouse embryos. Spontaneous conversion of (263)NGR and/or (501)NGR to iso-DGR possibly explains this enigma, i.e. ligation of iso-DGR by alphavbeta3 integrin may allow cells to assemble FN. Partial modification of (263)NGR to DGR or iso-DGR was detected in purified plasma FN by mass spectrometry. To test functions of the conversion, one or both NGR sequences were mutated to QGR in recombinant N-terminal 70-kDa construct of FN (70K), full-length FN, or FN-RGE. The mutations did not affect the binding of soluble 70K to already adherent fibroblasts or the ability of soluble 70K to compete with non-mutant FN or FN-RGE for binding to FN assembly sites. Non-mutant FN and FN-N263Q/N501Q with both NGRs mutated to QGRs were assembled equally well by adherent fibroblasts. FN-RGE and FN-RGE-N263Q/N501Q were also assembled equally well. Although substrate-bound 70K mediated cell adhesion in the presence of 1 mm Mn(2+) by a mechanism that was inhibited by cyclic RGD peptide, the peptide did not inhibit 70K binding to cell surface. Mutations of the NGR sequences had no effect on Mn(2+)-enhanced cell adhesion to adsorbed 70K but caused a decrease in cell adhesion to reduced and alkylated 70K. These results demonstrate that iso-DGR sequences spontaneously converted from NGR are cryptic and do not mediate the interaction of the 70K region of FN with the cell surface during FN assembly.


Early-onset anorexia nervosa in girls with Asperger syndrome.
Eating disorders frequently occur in conjunction with autism spectrum disorders, posing diagnostic and therapeutic difficulties. The comorbidity of anorexia nervosa and Asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis. The authors are presenting the cases of an eleven-year-old girl and a five-and-a-half-year-old girl with comorbid eating disorders and Asperger syndrome.


[Application of SNP-arrays in hematological malignancies - review].
Single Nucleotide Polymorphism (SNP) is a DNA sequence variation caused by the mutation at the level of genomic nucleotides. It has been reported as the third generation of genetic markers. The SNP-arrays, based on the principle of SNP, plays an important role in disease research mainly for genomic detection of predisposing genes. As a convenient, confident, sensitive and efficient technique, SNP arrays could be applicable for the multiple-point interaction analysis of candidate genes, making it a promising and powerful method for DNA analysis. Hematological malignancies consist of various categories and their incidence is rising significantly. A multiple-point gene interaction has been reported as the essential pathogenetic mechanism of these diseases. This review illustrates the process of SNP-arrays in genome-wide assay and the application of this technique to the pathogenesis, clinical manifestation, therapeutic response and the prognosis of the hematological malignancies, including leukemia, malignant lymphoma, juvenile myelo-monocytic leukemia, myelodysplastic syndrome, multiple myeloma and so on.


Mechanism of Linolenic Acid-induced Inhibition of Photosynthetic Electron Transport.
The effect of linolenic acid on photosynthetic electron transport reactions in chloroplasts has been localized at a site on the donor side of photosystem I and at two functionally distinct sites in photosystem II.In photosystem I, an increase in the electron transport rate occurs in the presence of 10 to 100 micromolar linolenic acid, followed by a decline in rate from 100 to 200 micromolar linolenic acid. The increase may result from an alteration of membrane structure that allows greater reactivity of the artificial donors 2,6-dichlorophenolindophenol (DPIP) and N,N,N',N'-tetramethyl-p-phenylenediamine with plastocyanin. The decrease is due to loss of plastocyanin from the membrane since addition of purified plastocyanin to treated and washed chloroplasts leads to the reestablishment of photosystem I rates.In photosystem II, a reversible site and an irreversible site of inhibition have been located. At the irreversible site, there is a time-dependent loss of the loosely bound pool of Mn implicated in the water-splitting mechanism. At the reversible site, the photochemical charge separation is rapidly inhibited as evidenced by the high initial fluorescence yield upon illumination and the inhibition of artificial donor reactions in NH(2)OH-washed chloroplasts. When chloroplasts are washed after treatment with linolenic acid, the fluorescence returns to its original low value and there is a resumption of artificial donor activity from diphenylcarbazide --> DPIP. This reversible inhibition of the photoact is a unique characteristic of linolenic acid and suggests evidence for a new mode of inhibition of photosystem II.


Water transport in the kidney and nephrogenic diabetes insipidus.
Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.


Preparation of Molecularly Imprinted Mesoporous Materials for Highly Enhancing Adsorption Performance of Cytochrome C.
Molecularly imprinted mesoporous materials (MIMs) were synthesized to improve the adsorption performance of Cytochrome c (Cyt c) by using an imidazolium-based amphiphilic ionic liquid 1-octadecyl-3-methylimidazolium chloride (C18MIMCl) as surfactant in aqueous solution via the epitope imprinting approach. The surface-exposed C-terminus nonapeptide of Cyt c (residues 96⁻104, AYLKKATNE) was utilized as the imprinted template. The nitrogen adsorption-desorption, thermo-gravimetric analysis, and transmission electron microscopy verified the successful preparation of MIMs with ordered mesoporous structure. The adsorption isotherm studies showed that the obtained MIMs exhibited superior adsorption capacity toward Cyt c of 86.47 mg·g-1 because of the high specific surface areas of 824 m²·g-1, and the appropriate pore size promoted the mass transfer of Cyt c, causing a rapid adsorption equilibrium within 20 min. Furthermore, these MIMs still remained excellent selectivity and recognition ability according to the selective as well as the competitive adsorption studies, suggesting that the molecularly imprinted mesoporous materials is expected to be used in the field of highly efficient separation and enrichment of proteins.


Comparative topography of the immunoreactive alpha-melanocyte-stimulating hormone neuronal systems in the brains of horses and rats.
The present study describes and compares the topography of alpha-melanocyte-stimulating hormone (alpha-MSH)-immunoreactive neurons in the forebrain of rats and horses. Two groups of immunoreactive cells were present in both species. These groups were distinguished by their cross-immunoreactivity and topography. The topography of cell bodies with cross-immunoreactivity for peptides derived from pro-opiomelanocortin (POMC) including adrenocorticotropin, 16K, alpha-MSH and beta-endorphin was similar in both species. However, the topography of perikarya which stained only for alpha-MSH, and not for other POMC-derived neuropeptides, was subject to pronounced species differences. In rats, perikarya which stained only for alpha-MSH (alpha 2-system) have a specific distribution in the dorsal and lateral hypothalamic regions from the level of the midoptic chiasm to the premamillary region of the posterior hypothalamus. At anterior levels of the rat brain, the cells are bipolar and oriented horizontally. Posteriorly, all alpha 2-group perikarya are stellate in rats. In the equine species, alpha 2-group cell bodies occupy a shorter anterioposterior field extending from the posterior level of the paraventricular nucleus to the supramamillary nucleus. Stellate cells are mixed with bipolar cells at all levels of the alpha 2-field in the equine hypothalamus. Further, in contrast to the continuous cell group found in rats, the alpha 2-group divides into perifornical and periventricular subpopulations at posterior levels of the equine hypothalamus. The results from this study suggest that the topography of the arcuate opiocortin cell pool, which contains peptides derived from POMC, is similar in phylogenetically diverse mammalian species whereas the topography of the cell pool staining only for alpha-MSH is subject to species differences. In both species, the major terminus of alpha 2-neurons appears to be the cerebral cortex and hippocampus. It has been proposed that alpha-MSH is one of several neuropeptides concerned with memory and behavior. Thus, species differences in the topography of the alpha 2-pool may reflect evolutionary changes in the importance of this peptide to these physiological processes.


Sequential development of enzymes of gluconeogenesis and glucose synthesis in fetal goat liver.
The development of three key gluconeogenic enzymes, viz. phosphoenolpyruvate carboxykinase, fructose 1.6-bisphosphatase and glucose 6-phosphatase, and the gluconeogensis by liver slices were studied during development of goat fetus. The three enzymes develop in a sequential and time dependent manner, and the glucose 6-phosphatase develops last at around 100 days of gestation. Glucose synthesis by fetal liver slices was observed after 120 days of gestation. It may be concluded that the gluconeogenic sequence is operative well before birth and the goat fetus synthesizes its own glucose after 100 days of gestation.


Effects of positive and negative reinforcement on daily living skills in chronic psychiatric patients in community residences.
The effects of contingent positive and negative reinforcement on adaptive behavior and mood were examined in a sample of 36 chronic, psychiatric outpatients. Group 1 received contingent positive token reinforcement to improve daily living skills, group 2 received a negative reinforcement procedure based on removal of free-tokens, and group 3 was a no-treatment control. Subjects were assessed via a weekly daily living checklist and were pre- and posttested on the Profile of Mood States (POMS). Significant differences were found between the control and treatment groups on both total activities of daily living and among five individual targeted behaviors. Mood states did not differ among the groups, which indicates benign effects of negative reinforcement. The findings of this study are relevant to the treatment of the serious and persistently mentally ill.


A novel method to monitor human stress states using ultra-short-term ECG spectral feature.
Electrocardiogram (ECG) signal represents autonomous nervous system responses to human emotional states. This research demonstrates that the spectral ECG features within ultra-short-term window duration (10-sec) could be utilized to monitor human emotional states. Experiments were conducted with five different stress protocols including mental and physical tasks. Experimental results showed feasible classification performance of ECG spectral features compared to that of HRV parameters. The averaged classification accuracy across 13 subjects and all stress protocols was 81.16% using Naïve Bayes algorithm. In addition, the results showed stress responses in mental arithmetic tasks was the most separable from those in resting states (87.31%) compared to the other stress situations.


Carbon isotopic composition and oxygen isotopic enrichment in phloem and total leaf organic matter of European beech (Fagus sylvatica L.) along a climate gradient.
This study investigated the influence of climate on the carbon isotopic composition (sigma13C) and oxygen isotopic enrichment (delta18O) above the source water of different organic matter pools in European beech. In July and September 2002, sigma13C and delta18O were determined in phloem carbohydrates and in bulk foliage of adult beech trees along a transect from central Germany to southern France, where beech reaches its southernmost distributional limit. The data were related to meteorological and physiological parameters. The climate along the transect stretches from temperate [subcontinental (SC)] to submediterranean (SM). Both sigma13Cleaf and delta18Oleaf were representative of site-specific long-term environmental conditions. sigma13C of leaves collected in September was indicative of stomatal conductance, vapour pressure deficit (VPD) and radiation availability of the current growing season. delta18O was mainly correlated to mean growing season relative humidity (RH) and VPD. In contrast to the leaves, sigma13Cphloem varied considerably between July and September and was well correlated with canopy stomatal conductance (Gs) in a 2 d integral prior to phloem sampling. The relationship between sigma13C and delta18O in both leaves and phloem sap points, however, to a combined influence of stomatal conductance and photosynthetic capacity on the variation of sigma13C along the transect. delta18Ophloem could be described by applying a model that included 18O fractionation associated with water exchange between the leaf and the atmosphere and with the production of organic matter. Hence, isotope signatures can be used as effective tools to assess the water balance of beech, and thus, help predict the effects of climatic change on one of the ecologically and economically most important tree species in Central Europe.


Anteroinferior cerebellar artery aneurysms: surgical approaches and outcomes--a review of 34 cases.
Anteroinferior cerebellar artery (AICA) aneurysms are rare lesions whose treatment requires expertise in vascular, endovascular, and cranial base surgery. This article presents the largest series treated at one center. We retrospectively analyzed presenting symptoms, aneurysm characteristics, surgical approaches, postoperative outcomes, and the application of endovascular techniques. We found 32 patients with 34 AICA aneurysms (11 men and 21 women; age range, 6-77 yr; mean age, 51 yr). Twenty-one aneurysms had ruptured; 13 were unruptured. Seven of the unruptured aneurysms presented with brainstem compression, and six were found incidentally. Surgical approaches included the retrosigmoid, far-lateral transcochlear, translabyrinthine, and orbitozygomatic. Eighteen patients (56%) had neurological complications. Thirty aneurysms were at proximal locations, and four were distal. Intraoperative hypothermic cardiac arrest was used to clip eight giant aneurysms. Follow-up was available in 56% of the patients for a mean of 41 months. The mean Glasgow Outcome Scale scores at discharge were not significantly different from the patients' status at their initial assessment. We recommend the standard retrosigmoid approach for treating small to medium aneurysms involving the lower two-thirds of the clivus or distal AICA aneurysms. Cranial base approaches are recommended for large or giant aneurysms or for those proximal to the emergence of the AICA from the basilar trunk. Hypothermic cardiac arrest facilitates dissection of giant aneurysms. Endovascular treatment is a useful adjunct for treating residual aneurysms but did not provide definitive treatment in any of our patients.


Role of mitochondria in the origin of chloroplast starch grains: description of the phenomenon.
By phase microscopic observation of living palisade parenchyma cells in sections of Nicotiana excelsior leaves from plants previously placed in the dark for 72 hours, 30 to 45 minutes of light is found to induce mitochondria to remain stationary within the concavity of the chloroplasts and become round. Extending the illumination period to 60 to 90 minutes causes the stationary mitochondria in the concavity to change from a translucent to an opaque appearance, the change coinciding with the first appearance of starch as detected by blue staining of the grains with I(2)-KI. It is speculated that an interaction bearing some resemblance to the previously described interaction between mitochondria and the mobile phase of the chloroplasts may also operate in the starch grain phenomenon.


HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung.
Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression) in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), the zinc storage protein, metallothionein (MT1), and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats ± dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. HIV-1 transgene expression increased the liver-specific expression of TNFα, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further, HIV-1 transgene expression decreased intracellular zinc levels and increased expression of ZIP1 in the alveolar macrophages, a pattern consistent with zinc deficiency, and decreased their bacterial phagocytic capacity. Interestingly, dietary zinc supplementation in HIV-1 transgenic rats decreased gene expression of TNFα, MT1, and ZNT1 in the liver while simultaneously increasing their expression in the lung. In parallel, zinc supplementation increased alveolar macrophage intracellular zinc levels and bacterial phagocytic capacity in HIV-1 transgenic rats. Taken together, these findings suggest that chronic HIV-1-related protein expression causes liver inflammation and zinc sequestration, which in turn limits zinc bioavailability in the lung and thereby impairs alveolar macrophage phagocytic function. Importantly, dietary zinc supplementation decreases liver inflammation and zinc sequestration and restores alveolar macrophage phagocytic function in HIV-1 transgenic rats, a result with potential clinical implications for improving lung health in HIV-1-infected individuals.


Encoding Cell-Instructive Cues to PEG-Based Hydrogels via Triple Helical Peptide Assembly.
Effective synthetic tissue engineering scaffolds mimic the structure and composition of natural extracellular matrix (ECM) to promote optimal cellular adhesion, proliferation, and differentiation. Among many proteins of the ECM, collagen and fibronectin are known to play a key role in the scaffold's structural integrity as well as its ability to support cell adhesion. Here, we present photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels displaying collagen mimetic peptides (CMPs) that can be further conjugated to bioactive molecules via CMP-CMP triple helix association. Pre-formed PEGDA-CMP hydrogels can be encoded with varying concentration of cell-signaling CMP-RGD peptides similar to cell adhesive fibronectin decorating the collagen fibrous network by non-covalent binding. Furthermore, the triple helix mediated encoding allows facile generation of spatial gradients and patterns of cell-instructive cues across the cell scaffold that simulate distribution of insoluble factors in the natural ECM.


Ice/Water Interface: Zeta Potential, Point of Zero Charge, and Hydrophobicity.
The ice/water interface is a common and important part of many biological, environmental, and technological systems. In contrast to its importance, the system has not been extensively studied and is not well understood. Therefore, in this paper the properties of the H(2)O ice/water and D(2)O ice/water interfaces were investigated. Although the zeta potential vs pH data points were significantly scattered, it was determined that the isoelectric point (iep) of D(2)O ice particles in water at 3.5 degrees C containing 10(-3) M NaCl occurs at about pH 3.0. The negative values of the zeta potential, calculated from the electrophoretic mobility, seem to decrease with decreasing content of NaCl, while the iep shifts to a higher pH. The point of zero charge (pzc) of D(2)O ice and H(2)O ice, determined by changes in pH of 10(-4) M NaCl aqueous solution at 0.5 degrees C after the ice particle addition, was found to be very different from the iep and equal to pH 7.0 +/- 0.5. The shift of the iep with NaCl concentration and the difference in the positions of the iep and pzc on the pH scale point to complex specific adsorption of ions at the interface. Interestingly, similar values of iep and pzc were found for very different systems, such as hydrophilic ice and highly hydrophobic hexadecane droplets in water. A comparison of the zeta potential vs pH curves for hydrophilic ice and hydrophobic materials that do not possess dissociative functional groups at the interface (diamond, air bubbles, bacteria, and hexadecane) indicated that all of them have an iep near pH 3.5. These results indicate that the zeta potential and surface charge data alone cannot be used to delineate the electrochemical properties of a given water/moiety interface because similar electrical properties do not necessary mean a similar structure of the interfacial region. A good example is the aliphatic hydrocarbon/water interface in comparison to the ice/water interface. Although the experiments were carried out with care, both the zeta potential, measured with a precise ZetaPlus meter, and DeltapH values (a measure of surface charge) vs pH were significantly scattered, and the origin of dissemination of the data points was not established. Differently charged ice particles and not fully equilibrium conditions at the ice/water interface may have been responsible for the dissemination of the data. Copyright 1999 Academic Press.


In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions.
In vitro selection methods provide rapid and extremely powerful tools for elucidating interactions within and between macromolecules. Here, we describe the development of an in vitro selection procedure that permits the rapid isolation and evaluation of functional hairpin ribozymes from a complex pool of sequence variants containing an extremely low frequency of catalytically proficient molecules. We have used this method to analyze the sequence requirements of two regions of the ribozyme-substrate complex: a 7-nucleotide internal loop within the ribozyme that is essential for catalytic function and substrate sequences surrounding the cleavage-ligation site. Results indicate that only 3 of the 16,384 internal loop variants examined have high cleavage and ligation activity and that the ribozyme has a strong requirement for guanosine immediately 3' to the cleavage-ligation site.


Electronically excited states of protonated aromatic molecules: benzaldehyde.
The photofragmentation spectrum of protonated benzaldehyde has been recorded in the 435-385 nm wavelength range. The first excited state is a pipi* state, strongly red shifted compared to the pipi* state of neutral benzaldehyde. The spectrum presents well resolved vibronic bands in contrast to some other protonated aromatic molecules like benzene or tryptophan in which the excited state dynamics is so fast that no vibrational structure can be observed. The bands can be assigned on the basis of a Franck-Condon analysis using ground and excited state frequencies calculated at the CC2/TZVP level.


The common bilio-pancreatic channel syndrome in childhood.
An abnormally long common bilio-pancreatic channel has been found in association with choledochal cysts and biliary strictures in childhood. It may also present with recurrent abdominal pain, vomiting, hyperamylasaemia and jaundice. This has been termed the common channel syndrome (CCS). Two cases with the CCS presenting early in childhood are reported together with a review of the literature. Open sphincteroplasty was performed in both cases with a satisfactory outcome.


Elderly patients with pelvic fracture: interventions and outcomes.
We examined the outcome of elderly trauma patients with pelvic fractures. Patients 65 years of age and older (elderly) with pelvic fractures were retrospectively compared with patients younger than 65 years with pelvic fractures and also with elderly patients without fracture. Over the study period, 1223 patients sustained a pelvic fracture (younger than 65 years, n=1066, 87.2%; elderly, n=157, 12.8%). These patients were also compared with 1770 elderly patients with blunt trauma without fracture. Although the pelvic fracture patients were equally matched for Injury Severity Score (21.2 +/- 13.4 nonelderly vs. 20.5 +/- 13.6 elderly), hospital length of stay was increased in the elderly (12.5 +/- 13.1 days vs. 11.5 +/- 14.1 days) and they had a higher mortality rate (20.4% [32 of 157] vs. 8.3% 88 of 10661). The elderly without fracture also had a higher mortality rate when compared with the younger patients (10.9% [191 of 1760]; P < 0.03). The elderly were more likely to die from multisystem organ failure (25.0% [eight of 32] vs. 10.2% [nine of 88]), whereas the nonelderly group was more likely to die from exsanguination (45.5% [40 of 88] younger than 65 years vs. 21.9% [seven of 32] 65 years or older; P < 0.05). Elderly patients with pelvic fracture have worse outcomes than their younger counterparts despite aggressive management at a Level I trauma center.


Evaluation of dermatological effects of cosmetic formulations containing Saccharomyces cerevisiae extract and vitamins.
Saccharomyces cerevisiae extract (SCE) is used in cosmetics since it can act in oxidative stress and improve skin conditions. This study investigated dermatological effects of cosmetic formulations containing SCE and/or vitamins A, C and E. The formulation studied was supplemented or not (F1: vehicle) with vitamins A, C and E esters (F2) or with SCE (F3) or with the combination of vitamins and SCE (F4). Formulations were patch tested on back skin of volunteers. For efficacy studies, formulations were applied on volunteers and transepidermal water loss (TEWL), skin moisture (SM), skin microrelief (SMR) and free radicals protection were analysed after 3h, 15 and 30 days of application. Volunteers were also asked about efficacy perception. It was observed that F4 provoked a slight erythema in one volunteer. All formulations enhanced forearm SM. Only F3 and F4 presented long term effects on SMR and showed higher texture values; F3 had the highest brightness values. Our results suggest that vitamins and SCE showed effects in SM and SMR. Only formulations containing SC had long term effects in the improvement of SMR. Thus, these kinds of evaluations are very important in cosmetics development to evaluate the best risk and benefit correlation.


Effects of Chilling and ABA on [H]Gibberellin A(4) Metabolism in Somatic Embryos of Grape (Vitis vinifera L. x V. rupestris Scheele).
Previous work has indicated that changes in gibberellin (GA) metabolism may be involved in chilling-induced release from dormancy in somatic embryos of grape (Vitis vinifera L. x V. rupestris Scheele). We have chilled somatic embryos of grape for 2, 4, or 8 weeks, then incubated them with [(3)H]GA(4) (of high specific activity, 4.81 x 10(10) becquerel per millimole) for 48 hours at 26 degrees C. Chilling had little effect on the total amount of free [(3)H]GA-like metabolites formed during incubation at 26 degrees C, but did change the relative proportions of individual metabolites. The amount of highly water-soluble [(3)H] metabolites formed at 26 degrees C decreased in embryos chilled for 4 or 8 weeks. The concentration of endogenous GA precursors (e.g., GA(12) aldehyde-, kaurene-, and kaurenoic acid-like substances) increased in embryos chilled for 4 or 8 weeks. Treatment with abscisic acid (ABA) (known to inhibit germination in grape embryos) concurrent with [(3)H]GA(4) treatment at 26 degrees C, reduced the uptake of [(3)H] GA(4) but had little effect on the qualitative spectrum of metabolites. However, in the embryos chilled for 8 weeks and then treated with ABA for 48 hours at 26 degrees C, there was a higher concentration of GA precursors than in untreated control embryos. Chilled embryos thus have an enhanced potential for an increase in free GAs through synthesis from increased amounts of GA precursors, or through a reduced ability to form highly water-soluble GA metabolites (i.e., GA conjugates or polyhydroxylated free GAs).


A Novel Occupancy Mapping Framework for Risk-Aware Path Planning in Unstructured Environments.
In the context of autonomous robots, one of the most important tasks is to prevent potential damage to the robot during navigation. For this purpose, it is often assumed that one must deal with known probabilistic obstacles, then compute the probability of collision with each obstacle. However, in complex scenarios or unstructured environments, it might be difficult to detect such obstacles. In these cases, a metric map is used, where each position stores the information of occupancy. The most common type of metric map is the Bayesian occupancy map. However, this type of map is not well suited for computing risk assessments for continuous paths due to its discrete nature. Hence, we introduce a novel type of map called the Lambda Field, which is specially designed for risk assessment. We first propose a way to compute such a map and the expectation of a generic risk over a path. Then, we demonstrate the benefits of our generic formulation with a use case defining the risk as the expected collision force over a path. Using this risk definition and the Lambda Field, we show that our framework is capable of doing classical path planning while having a physical-based metric. Furthermore, the Lambda Field gives a natural way to deal with unstructured environments, such as tall grass. Where standard environment representations would always generate trajectories going around such obstacles, our framework allows the robot to go through the grass while being aware of the risk taken.