The DSM-5 effect: psychological characteristics of new patients affected by Binge Eating Disorder following the criteria of the DSM-5 in a sample of severe obese patients.
The current study evaluated whether or not there were significant differences in psychopathological traits between three groups of individuals. The first was a group of patients seeking bariatric surgery diagnosed as being affected by Binge Eating Disorder (BED), according to the new criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. This group (NEW BED group) did not meet BED diagnosis following the previous criteria listed in the DSM-IV-TR. The second group of individuals was composed of severely obese patients seeking bariatric surgery not affected by an eating disorder, according to the diagnostic criteria of the DSM-5 (OB group). The third group was composed of individuals within a healthy weight range (Control group). 94 severely obese patients (33 in the NEW BED group and 61 in the OB group) were compared to the Control group including 41 participants on depression, anxiety and eating habits. The NEW BED scored significantly higher than the OB group on the Beck Depression Inventory, both the subscales of the State Trait Anxiety Inventory, on disinhibition and hunger subscales of the Three-Factor Eating Questionnaire and on many subscales of the Eating Disorders Inventory. The new, less restrictive diagnostic criteria for BED of the DSM-5 are useful in identifying obese patients affected by severe psychopathology and dysfunctional eating habits.


Effect of organotin compounds and hexachlorophene on brain adenosine cyclic 3',5'-monophosphate metabolism.
The effect of triethyltin (TET), triphenyltin (TPT), hexachlorophene (HCP) and cuprizone on adenosine cyclic 3',5'-monophosphate (cyclic AMP) production in rat brain was examined both in vitro and in vivo. TET and TPT inhibited basal adenylate cyclase activity of brain homogenate at a concentration as low as 1 microM in vitro but these compounds had no effect on norepinephrine (NE) and dopamine(DA)-stimluated enzyme activity. HCP and cuprizone failed to inhibit adenylate cyclase activity. In vivo TET given intravenously at a dose rate of 10 mg/kg decreased the cyclic AMP content of cerebrum, but not of medulla. TPT and HCP give intravenously and intraperitoneally respectively failed to decrease the cyclic AMP content of the cerebrum. In the case of TET the reduction in cyclic AMP content of the cerebrum was prevented by maintaining the rats normothermic after treatment. On the basis of these results the inhibition of adenylate cyclase produced by TET in brain homogenates in vitro would not appear to be involved in the development of nervous changes associated with acute TET toxicity, or in the production of progressive brain oedema caused by TET, HCP and cuprizone.


Cryptococcus neoformans shows a remarkable genotypic diversity in Brazil.
The genotypic diversity of Brazilian Cryptococcus neoformans strains was analyzed. The majority of the samples were alphaA (65%), followed by alphaB (17.5%), alphaD (9%), alphaAaD hybrids (5%), and alphaC (3.5%). A considerable genotypic diversity occurred within C. neoformans var. grubii, and a new amplified fragment length polymorphism genotype, 1B, was recognized.


Development of new structural alerts suitable for chemical category formation for assigning covalent and non-covalent mechanisms relevant to DNA binding.
The need to assess the ability of a chemical to act as a mutagen is one of the primary requirements in regulatory toxicology. Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories and read-across for the assessment of toxicological endpoints. One of the key steps in the development of chemical categories for mutagenicity is defining the mechanistic organic chemistry associated with the formation of a covalent bond between DNA and an exogenous chemical. To this end this study has analysed, by use of a large set of mutagenicity data (Ames test), the mechanistic coverage of a recently published set of in silico structural alerts developed for category formation. The results show that the majority of chemicals with a positive result in the Ames test were assigned at least one covalent binding mechanism related to the formation of a DNA adduct. The remaining chemicals with positive data in the Ames assay were subjected to a detailed mechanistic analysis from which 26 new structural alerts relating to covalent binding mechanisms were developed. In addition, structural alerts for radical and non-covalent intercalation mechanisms were also defined. The structural alerts outlined in this study are not intended to predict mutagenicity but rather to identify mechanisms associated with covalent and non-covalent DNA binding. This mechanistic profiling information can then be used to form chemical categories suitable for filling data gaps via read-across. A strategy for chemical category formation for mutagenicity is also presented.


Birth-weight charts and immigrant populations: A critical review.
There is an increasing body of literature focusing on differences in newborn size between different population subgroups defined by racial, ethnic, and immigration status. The interpretation of these differences as pathological or as merely reflecting normal variability is not straightforward and may have consequences for the provision of obstetric and neonatal care to minority populations. In this review, we critically assess some methodological issues affecting the assessment of newborn size and their potential implications for minority populations. In particular, we discuss the pros and cons of different types of newborn birth-weight (BW) charts (i.e., single local population-based references, minority-specific references, and a single international standard) to determine abnormal newborn size, with emphasis on immigrant populations. We conclude that size alone is not enough to inform clinical decisions and that all newborn size charts should be used as screening tools, not as diagnostic tools. Parental minority status may be regarded as a marker and used to further inquire about individual risk factors, particularly among immigrants who may not have a complete medical history in the new country. Finally, we outline areas for further research and recommendations for clinical practice.


Variations in early and late event-related components of the auditory evoked potential with task difficulty.
A variation in the difficulty of an auditory discrimination was used to investigate the relationship between the event-related P165, N2 and P3 components of the auditory evoked potential. Equivalent increases in the latencies of all 3 components were found with increased task difficulty. The P165 component, however, could be differentiated from the two later components since it increased in amplitude with increased task demands while the N2 and P3 amplitudes remained constant. It is suggested that the P165, N2 and P3 components comprise a functional sequence in the processing of rare events and possibly involved in a subject's preparations for the future.


Focal lesions following intracerebral gene therapy for mucopolysaccharidosis IIIA.
Mucopolysaccharidosis type IIIA (MPSIIIA) caused by recessive SGSH variants results in sulfamidase deficiency, leading to neurocognitive decline and death. No disease-modifying therapy is available. The AAVance gene therapy trial investigates AAVrh.10 overexpressing human sulfamidase (LYS-SAF302) delivered by intracerebral injection in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations were initiated in one patient to determine the cause. Clinical and MRI details were reviewed. Stereotactic needle biopsies of a lesion were performed; blood and CSF were sampled. All samples were used for viral studies. Immunohistochemistry, electron microscopy, and transcriptome analysis were performed on brain tissue of the patient and various controls. MRI revealed focal lesions around injection sites with onset from 3 months after therapy, progression until 7 months post therapy with subsequent stabilization and some regression. The patient had transient slight neurological signs and is following near-normal development. No evidence of viral or immunological/inflammatory cause was found. Immunohistochemistry showed immature oligodendrocytes and astrocytes, oligodendrocyte apoptosis, strong intracellular and extracellular sulfamidase expression and hardly detectable intracellular or extracellular heparan sulfate. No activation of the unfolded protein response was found. Results suggest that intracerebral gene therapy with local sulfamidase overexpression leads to dysfunction of transduced cells close to injection sites, with extracellular spilling of lysosomal enzymes. This alters extracellular matrix composition, depletes heparan sulfate, impairs astrocyte and oligodendrocyte function, and causes cystic white matter degeneration at the site of highest gene expression. The AAVance trial results will reveal the potential benefit-risk ratio of this therapy.


Clinical utility of a new protocol of cardiac computed tomography in dogs.
The characteristics of non-electrocardiography- and electrocardiography-gated multidetector computed tomography have not been extensively studied in veterinary clinics but it can be useful for cardiac imaging. This study aimed to ascertain the differences between non-electrocardiography and electrocardiography gating methods and to establish their clinical utility based on patient history. Six client-owned dogs (two with patent ductus arteriosus, two with heart base tumour, one with pericardial mesothelioma, and one with normal health) were included in this study. All the dogs were examined using a non-electrocardiography-gated scan, followed by a retrospective electrocardiography-gated scan. Images were reviewed to determine the optimal scan timing and R-R interval in non-electrocardiography- and electrocardiography-gated images, respectively, for detailed coronary artery imaging, diagnostic quality of the best coronary artery visualisation in non-electrocardiography- and electrocardiography-gated images through visual assessment of the main coronary artery branches, and branching patterns of the left coronary artery. Further, we compared the size and margin demarcation of the heart or pericardial lesions in non-electrocardiography- and electrocardiography-gated images obtained from patients with heart or pericardial tumours. The optimal scan timing and R-R interval were the second-scan timing and end-diastole (70%-90%), respectively. Second-scan non-electrocardiography-gated images allowed coronary artery evaluation, indicating high-grade quality in visual assessment, except for the septal branch. Electrocardiography-gated images, but not non-ECG-gated images, clearly revealed pericardial nodules in two dogs. Our findings suggest the respective clinical utilities of non-electrocardiography- or electrocardiography-gated imaging using high-slice cardiac computed tomography based on patient history.


Ureteral stone manipulation before extracorporeal shock wave lithotripsy.
We randomized 75 patients with solitary ureteral calculi that could not be dislodged by ureteral catheterization to receive instillation of saline, 2 per cent lidocaine viscous solution or dilute surgical lubricant before repeat stone manipulation with ureteral catheters. Of the stones irrigated with saline 76 per cent were returned to the pelvis along with 60 per cent of the lidocaine group and 48 per cent of the surgical lubricant treated stones. There was no statistical significance among the 3 groups. The success rates for upper, mid and lower ureteral stones were 80, 54 and 30 per cent, respectively. Of stones 0.5 cm. or less and between 0.6 and 1.0 cm. 77 and 72 per cent, respectively, were manipulated successfully but only 38 per cent of the stones larger than 1.0 cm. could be dislodged. Extracorporeal shock wave lithotripsy was successful in treating pelvic and ureteral stones, although higher kilovolt settings and additional shocks were necessary to fragment the ureteral stones completely. Percutaneous nephrostomy or ureteral meatotomy was required in 10 per cent of the patients with impacted ureteral stones following in situ extracorporeal shock wave lithotripsy but in only 4 per cent of the patients with stones successfully returned to the pelvis. Of the ureteral stones 17 per cent were treated with repeat extracorporeal shock wave lithotripsy. No patient with pelvic stones required repeat treatment. Retrograde manipulation of ureteral stones is an effective adjunctive procedure before extracorporeal shock wave lithotripsy.


Serum nitric oxide levels in children with celiac disease.
To determine serum nitric oxide levels in pediatric patients with celiac disease and to compare them with the results obtained after 1 year of gluten-free diet. We studied serum nitric oxide levels in 41 newly diagnosed patients with celiac disease. Serum levels of nitric oxide were reevaluated after 1 year of gluten-free diet in 23 of them. Mean age was 10.4 +/- 3.4 years (range 2-17 years). The levels of nitric oxide in pretreatment 41 patients with celiac disease and healthy children were detected as 198.33 +/- 20.22 micromol/L and 135.63 +/- 21.17 micromol/L, respectively (P = 0.0001). Serum nitric oxide level, measured in the blood samples 1 year after gluten-free diet, was 148.27 +/- 27.25 micromol/L (P = 0.001). Serum nitric oxide levels were statistically correlated with the degree of histologic changes in celiac disease. In the patients with celiac disease, pretreatment level of nitric oxide was not correlated with the levels of triglyceride, cholesterol, albumin, aspartate aminotransferase, alanine aminotransferase, or creatine kinase. We found correlations with the level of nitric oxide and Hb, mean corpuscular volume, and ferritin. Higher serum nitric oxide levels found in children who had not compliance with gluten-free diet suggested the role of serum nitric oxide as an indicator of diet compliance. Because determination of serum nitric oxide is a simple, rapid, cheap, noninvasive, and highly sensitive method for celiac disease, we think that this parameter can be used in the evaluation of diet compliance in children with celiac disease or even instead of gluten challenge, due to more noninvasive property.


All-optical control on a graphene-on-silicon waveguide modulator.
The hallmark of silicon photonics is in its low loss at the telecommunications wavelength, economic advantages and compatibility with CMOS design and fabrication processes. These advantages are however impeded by its relatively low Kerr coefficient that constrains the power and size scaling of nonlinear all-optical silicon photonic devices. Graphene, with its unprecedented high Kerr coefficient and uniquely thin-film structure, makes a good nonlinear material to be easily integrated onto all-optical silicon photonic waveguide devices. We study the design of all-optical graphene-on-silicon (GOS) waveguide modulators, and find the optimized performance of MW cm-2 in optical pump intensities and sub-mm device lengths. The improvements brought by the integration of graphene onto silicon photonic waveguides could bring us a step closer to realising compact all-optical control on a single chip.


Theoretical insight into the BH3·HCN adsorption on the Co(100) and Co(110) surfaces as hydrogen storage.
Fifteen configurations and adsorption energies of the adsorption sites of BH3∙∙∙HCN on Co(100) and Co(110) surfaces were investigated using the density functional theory. The results show that after BH3∙∙∙HCN is adsorbed, although there is no general behavior for the H∙∙∙H distances, the adsorption energies of BH3∙∙∙HCN are always far stronger than those of H2 on Co surfaces, suggesting that the dihydrogen-bonded complex, one kind of prospective material for reversible hydrogen storage, can be tightly adsorbed on the surfaces of metals. Thus, the attempts to store the significant amounts of H2 can be successful by the way that the dihydrogen-bonded complexes are adsorbed on the surfaces of metals. The stability and binding mechanism was analyzed by the Mulliken charge population and reduced density gradients (RDGs) methods. Graphical Abstract BH3···HCN adsorption on Co surface.


Nickel species analysis of human colonic tissue using liquid chromatography, gel electrophoresis and mass spectrometry.
Studies to specify metal-binding species, such as metalloproteins that are present in trace amounts in colonic cell cytosol, using chromatographic separation methods in combination with inductively coupled plasma mass spectrometry (ICP-MS) as element-specific detection require an optimised sample preparation regarding the solubilisation of the proteins. Focus should be taken to avoid metal contamination, enzymatic digestion by different proteases and oxidation. In this article different sample preparation methods are studied to find a suitable method for the isolation and characterisation of Ni species previously found in cytosols from normal and malignant tissues of the human colon. The total Ni concentrations of the cytosols were determined as well as the total protein content. Thus, a Ni-containing protein could be isolated from cytosols of malignant human colonic tissues using size-exclusion chromatography with ICP-MS for element-specific detection. Ni-containing species in the molecular mass range from 10,000 to 20,000 Da were found and pre-concentrated. The determination of the molecular mass of the species was performed through online coupling of reversed-phase chromatography with electrospray ionisation quadrupole time-of-flight MS. Using identical chromatographic conditions and ICP-MS the detected protein was shown to contain Ni.


A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for hemorrhagic fever with renal syndrome.
Candidate DNA vaccines for hemorrhagic fever with renal syndrome expressing the envelope glycoprotein genes of Hantaan (HTNV) or Puumala (PUUV) viruses were evaluated in an open-label, single-center Phase 1 study consisting of three vaccination groups of nine volunteers. The volunteers were vaccinated by particle-mediated epidermal delivery (PMED) three times at four-week intervals with the HTNV DNA vaccine, the PUUV DNA vaccine or both vaccines. At each dosing, the volunteers received 8 μg DNA/4 mg gold. There were no study-related serious adverse events, and all injection site pain was graded as mild. The most commonly reported systemic adverse events were fatigue, headache, malaise, myalgia, and lymphadenopathy. Blood samples were collected on days 0, 28, 56, 84, 140, and 180, and assayed for the presence of neutralizing antibodies. In the single vaccine groups, neutralizing antibodies to HTNV or PUUV were detected in 30% or 44% of individuals, respectively. In the combined vaccine group, 56% of the volunteers developed neutralizing antibodies to one or both viruses. These results demonstrate that the HTNV and PUUV DNA vaccines are safe and can be immunogenic in humans when delivered by PMED.


Phase-polarisation contrast for surface plasmon resonance biosensors.
A technique of phase-polarisation contrast (PPC) for the enhancement of the contrast of a surface plasmon resonance (SPR) intensity profile is proposed and experimentally realised. The technique exploits the peculiarities of light phase and polarisation behaviour under SPR. It applies to non-optimum SPR coupling conditions and enables one to lower the resonant minimum of reflected intensity nearly to zero, and hence to increase substantially the ratio of the intensity from the resonance to that at the minimum. We observed the contrast enhancement by more than one order of magnitude when we applied the PPC scheme. The PPC can be efficiently employed in commercial SPR sensors, as it significantly reduces restrictions on allowable parameters of SPR-supporting metal films and biomolecular layers immobilised on them, facilitates SPR observation, and increases the accuracy of SPR shift measurements.


Mycobacterium fortuitum peritoneal dialysis-related peritonitis in a child: A case report and review of the literature.
Non-tuberculous mycobacteria (NTM) are an uncommon but serious cause of peritoneal dialysis (PD)-related infections. NTM peritonitis typically necessitates PD catheter removal, PD withdrawal, and aggressive, prolonged antimicrobial treatment. Few reported cases of NTM peritonitis in the pediatric population exist. We describe a case of a 9-year-old boy on PD after kidney allograft failure who developed Mycobacterium fortuitum peritonitis, and we summarize the available literature on M. fortuitum peritonitis in pediatric patients receiving PD. Therapeutic options were limited by adverse medication effects and risk of drug-drug interactions in a patient with complex mental health comorbidities. Clofazimine presented an acceptable oral treatment option for long-term therapy in combination with ciprofloxacin and was well tolerated by this patient. Prompt PD catheter removal followed by 6 months of dual antimicrobial therapy resulted in a full recovery and successful re-transplantation with no infection relapse.


Continuing education needs as perceived by dietetic practitioners.
Educational needs of dietitians were identified by 232 practitioners in Ohio by means of a self-administered questionnaire. Three major knowledge areas--managerial science, nutritional care science, and behavioral, communicative, and socio-cultural science--were covered in 109 questions. The respondents perceived a need for more professional knowledge than for behavioral, communicative, and socio-cultural sciences. Greater need was expressed for skills in technical and human ability than for skills in conceptual ability, and generally for nutritional knowledge rather than application. The findings could form the basis for continuing education programs.


Association between medication literacy and medication adherence and the mediating effect of self-efficacy in older people with multimorbidity.
Multimorbidity has a significant impact on public health and primary care. Medication adherence is recognized as the most effective measure for managing and preventing multimorbidity. Studies have shown that medication literacy has a positive effect on medication adherence in patients with multimorbidity. However, limited knowledge exists regarding the underlying mechanisms of this relationship in older adults with multimorbidity. Therefore, the aim of this study was to investigate the mediating role of self-efficacy in the association between medication literacy and medication adherence in this population. This study employed a cross-sectional design and convenience sampling method to survey older patients with multimorbidity in six communities in Zhengzhou, China, from July 12, 2021, to December 15, 2021. Participants were assessed using a demographic questionnaire, the Chinese Version of the Medication Literacy Scale (C-MLS), the Self-Efficacy for Appropriate Medication Use Scale (SEAMS), and the Chinese Version of the Morisky Medication Adherence Scale-8 (C-MMAS-8). Data were analyzed using descriptive statistics, t-tests, one-way analysis of variance, Pearson correlation analysis, and mediation analysis. A total of 350 elderly patients met the inclusion criteria, and 328 valid questionnaires were collected. The mean age of the participants was 74.90 ± 7.37 years, with a slightly higher proportion of males (55.8%) than females (44.2%). The mean score for medication adherence was 4.85 ± 1.57, indicating poor medication adherence among the participants. Medication adherence scores varied significantly among participants of different ages, education levels, employment statuses and kinds of medication (p < 0.01). Scores for medication literacy and self-efficacy showed a significant positive correlation with medication adherence scores (all p < 0.001). The standardized coefficient for the total effect and direct effect of medication literacy on medication adherence was 0.268 (95% CI: 0.201, 0.335) and 0.187 (95% CI: 0.123, 0.252), respectively. After introducing self-efficacy into the model, the standardized coefficient for the indirect effect was 0.081 (95% CI: 0.049, 0.120), indicating that self-efficacy partially mediated the relationship between medication literacy and medication adherence, accounting for 30.22% of the total effect. This study might suggest that medication literacy indirectly affected medication adherence in older people with multimorbidity through self-efficacy. Health care providers should be aware of the importance of improving medication literacy and implement strategies aimed at increasing self-efficacy to achieve the goal of improving medication adherence in older adults with multimorbidity.


Syntheses, structures and properties of three new two-dimensional Cu(I)-Ln(III) heterometallic coordination polymers based on 2,2'-dipyridyl-5,5'-dicarboxylate ligands.
Three new two-dimensional Cu(I)-Ln(III) heterometallic coordination polymers [Ln(III)Cu2(I)(Hbpdc)4] · Cl · xH2O [Ln(III) = La(III), x = 8 (1); Ln(III) = Pr(III), x=9 (2); Ln(III) = Eu(III), x = 8 (3)] (H2bpdc = 2,2'-bipyridyl-5,5'-dicarboxylic acid) have been prepared under hydrothermal conditions and structurally characterized by elemental analyses, inductively coupled plasma atomic emission spectrometry (ICP-AES) analyses, IR spectra, X-ray photoelectron spectroscopy (XPS) and single-crystal X-ray diffraction. X-ray diffraction indicates that the isomorphic 1-3 display the two-dimensional sheet structure constructed from [Cu(I)(Hbpdc)2](-) fragments through Ln(3+) connectors. Moreover, the solid-state photoluminescence measurements of 3 indicate that the Eu(III) ions, Hbpdc(-) ligands and Cu(I) cations make contributions to its luminescent properties simultaneously.


A new anti-human Fc method to capture and analyze ADCs for characterization of drug distribution and the drug-to-antibody ratio in serum from pre-clinical species.
Antibody-drug conjugates (ADCs) are becoming a major class of oncology therapeutics. They combine monoclonal antibody specificity for over-expressed tumor antigens and the high cytoxicity of small molecular drugs (SMDs) and can therefore selectively kill tumor cells while minimizing toxicity to normal cells. Nevertheless, the premature deconjugation of ADCs in the circulation may trigger off target toxicity in patients. The released free drug level must be low in circulation for an extended period of time as well as the de-conjugation rate to ensure an acceptable therapeutic window. As a result, the assessment of the stability of the linker between payload and mAb in the systemic circulation is of paramount importance before entering in clinical trial. Here we report a new universal method to immunocapture and analyze by LC-MS the stability and distribution of ADCs in sera from relevant preclinical species (mouse, rat and cynomolgus monkey). Furthermore we demonstrated that this workflow can be applied to both ADCs with cleavable and non cleavable linkers. Last but not least, the results obtained in cynomolgus serum using immunoprecipitation and LC-MS analysis were cross validated using an ELISA orthogonal method. As the ligand used for immunoprecipitation is targeting the Fc part of mAb (CaptureSelect™ Human IgG-Fc PK Biotin), this protocol can be applied to analyze the stability of virtually all ADCs in sera for preclinical studies without the need to prepare specific molecular tools.


Tetrafungin, a new polyene macrolide antibiotic. II. Taxonomy of the producing organism and comparison with nystatin by means of high performance liquid chromatography.
Tetrafungin, a new polyene macrolide antibiotic, is produced by a Streptomyces strain identified as a new subspecies of Streptomyces albulus and named Streptomyces albulus subsp. tetrafungini. Tetrafungin and nystatin have been investigated and compared by HPLC. It has been demonstrated that tetrafungin and nystatin differ qualitatively in, at least, one component, and quantitatively in their relative amounts of common components.


Recommendations for addressing the translational gap between experimental and clinical research on amyloid diseases.
This paper is a report of recommendations for addressing translational challenges in amyloid disease research. They were developed during and following an international online workshop organized by the LINXS Institute of Advanced Neutron and X-Ray Science in March 2021. Key suggestions include improving cross-cultural communication between basic science and clinical research, increasing the influence of scientific societies and journals (vis-à-vis funding agencies and pharmaceutical companies), improving the dissemination of negative results, and strengthening the ethos of science.


Geldanamycin inhibits tyrosine phosphorylation-dependent NF-kappaB activation.
Hsp90 is a protein chaperone regulating the stability and activity of many signalling molecules. The requirement of Hsp90 activity in the NF-kappaB pathway has been recently reported by several authors using the Hsp90 ATPase inhibitor geldanamycin (GA), an anti-tumor drug. Hsp90 inhibition blocks the synthesis and activation of the IKK complex, the major kinases complex responsible for IkappaBalpha phosphorylation on serine 32 and 36, a key step for its degradation and the nuclear translocation of NF-kappaB. However, the effect of GA on other IkappaBalpha kinases, including tyrosine kinases, is unknown. In the present study, we investigated the effect of GA on NF-kappaB activation induced by sodium pervanadate (PV), a tyrosine phosphatase inhibitor triggering c-Src-mediated tyrosine phosphorylation of IkappaBalpha. We report for the first time that GA inhibits PV-induced IkappaBalpha tyrosine phosphorylation and degradation. Using an in vitro kinase assay, we demonstrated that GA inhibits the activity of c-Src as an IkappaBalpha tyrosine kinase, but not its cellular expression. As a result, GA blocked PV-induced NF-kappaB DNA-binding activity on an exogenous kappaB element and on the endogenous ikappabalpha promoter, thereby inhibiting ikappabalpha transcription. Finally, we demonstrated that, despite NF-kappaB inhibition, pre-treatment with GA does not potentiate PV-induced apoptosis. We conclude that c-Src requires Hsp90 for its tyrosine kinase activity, and its inhibition by GA blocks c-Src-dependent signalling pathways, such as NF-kappaB activation induced by sodium pervanadate. The effect of GA on PV-induced apoptosis is discussed in the light of recent publications in the literature.


Evolution of the scrambled germline gene encoding alpha-telomere binding protein in three hypotrichous ciliates.
The micronuclear genes encoding alpha-telomere-binding protein (alphaTP) in Oxytricha trifallax and Stylonychia mytilus contain multiple internal eliminated segments, or IESs, that divide the gene into multiple parts called macronuclear destined segments, or MDSs. The MDSs have become disordered, or scrambled, during evolution. The scrambled structures of the alphaTP genes in Oxytricha trifallax and S. mytilus have been compared with the previously published scrambled structure of the alphaTP gene in O. nova. The scrambled patterns of the alphaTP gene in the three species are similar but show significant differences. The micronuclear genes in O. nova and S. mytilus consist of 13 IESs and 14 MDSs, but the gene in O. trifallax is divided into three additional MDSs by the presence of three additional IESs, believed to have been inserted into the O. trifallax alphaTP gene after divergence of O. trifallax from the other two species. Corresponding IESs among the three species have shifted along the DNA during evolution, presumably by a mutational mechanism that changes the short repeat sequences that flank IESs. The IESs also have changed markedly in length by insertion and/or deletion of nucleotides. Comparison of the putative alphaTP amino acid sequences in the three species reveals three conserved and three nonconserved domains. The 5' nontranslated regions of the gene-sized molecules encoding alphaTP contain several conserved segments, and the 3' nontranscribed trailer contains one conserved segment.


Surgical mask-to-mouth ventilation as an alternative ventilation technique during CPR: A crossover randomized controlled trial.
Chest compression with rescue breathing improves outcomes in cardiac arrest. However, the efficacy of rescue breathing through surgical masks has not been investigated. We aimed to compare the tidal volume generated by mouth-to-mouth ventilation (MMV) with that generated by surgical mask-to-mouth ventilation (SMV), mouth-to-surgical mask ventilation (MSV), and surgical mask-to-surgical mask ventilation (SSV) in a manikin. A crossover randomized controlled trial was conducted in 42 medical personnel volunteers randomly assigned to perform four ventilation techniques: MMV (no protective equipment), SMV (participant wearing a mask), MSV (manikin wearing a mask), and SSV, (both participant and manikin wearing a mask). The average tidal volume and the proportion of adequate ventilation, evaluated using a manikin, were compared across different ventilation methods. The average tidal volume of MMV (828 ± 278 ml) was significantly higher than those of the MSV (648 ± 250 ml, P < 0.001) and SSV (466 ± 301 ml, P < 0.001), but not SMV (744 ± 288 ml, P = 0.054). Adequate ventilation was achieved in 144/168 (85.7%) cases in the MMV group, a proportion significantly higher than in the SMV (77.4%, P = 0.02), MSV (66.7%, P < 0.001) and SSV (39.3%, P < 0.001) groups. The willingness to perform SMV was higher than that to perform MMV. MMV resulted in a superior average tidal volume when compared to both MSV and SSV. However, SMV achieved a comparable average tidal volume to MMV.


Detection of Fibril Nucleation in Micrometer-Sized Protein Condensates and Suppression of Sup35NM Fibril Nucleation by Liquid-Liquid Phase Separation.
Elucidating the link between amyloid fibril formation and liquid-liquid phase separation (LLPS) is crucial in understanding the pathologies of various intractable human diseases. However, the effect of condensed protein droplets generated by LLPS on nucleation (the initial step of amyloid formation) remains unclear because of the lack of available quantitative analysis techniques. This study aimed to develop a measurement method for the amyloid droplet nucleation rate based on image analysis. We developed a method to fix micrometer-sized droplets in gel for long-term observation of protein droplets with known droplet volumes. By combining this method with image analysis, we determined the nucleation dynamics in droplets of a prion disease model protein, Sup35NM, at the single-event level. We found that the nucleation was unexpectedly suppressed by LLPS above the critical concentration (C*) and enhanced below C*. We also revealed that the lag time in the Thioflavin T assay, a semi-quantitative parameter of amyloid nucleation rate, does not necessarily reflect nucleation tendencies in droplets. Our results suggest that LLPS can suppress amyloid nucleation, contrary to the conventional hypothesis that LLPS enhances it. We believe that the proposed quantitative analytical method will provide insights into the role of LLPS from a pathological perspective.


[Cervical vertebral hemangioma with aggressive behavior].
Hemangiomas are the most common primary tumors of the spine. Mainly asymptomatic Incidental finding when performing an imaging study. The incidence reported at autopsies is 11% in the spine, multifocal lesions are present in 25 to 30% of cases. Vertebral cervical hemangioma with benign and stable characteristics that underwent surgical treatment, observing aggressive post-surgical behavior two months later. The approach to vertebral pathology is algorithmic and protocolized, it is necessary to determine the treatment based on the overall understanding of the disease and according to the clinical practice guidelines.


Pediatric emergency resuscitative thoracotomy: A Western Trauma Association, Pediatric Trauma Society, and Eastern Association for the Surgery of Trauma collaborative critical decisions algorithm.
Literature synthesis and expert opinion, Level V.


Attempts to demonstrate cell-mediated immune response during Mycoplasma suipneumoniae infection of pigs.
Measurements of lymphocyte transformation and skin sensitivity were used to investigate whether pigs previously inoculated with Mycoplasma suipneumoniae would show a T-lymphocyte-mediated immune response. In the lymphocyte transformation test blood lymphocytes, obtained at various intervals after intranasal inoculation of M suipneumoniae cultures, were incubated with specific antigen and the degree of transformation was assessed by 14C-thymidine uptake. Reaction to intradermal antigen was assessed both grossly and histologically. Significant lymphocyte transformation was first obtained at approximately 15 weeks and was demonstrable up to the maximum observation period of 44 weeks after inoculation; this corresponded to the stage of progressive recovery from infection earlier described. Skin hypersensitivity, characterised histologically by perivascular mononuclear cell accumulation in the dermis, was demonstrated in all tests performed between 20 and 46 weeks after inoculation on previously infected pigs, and was apparently enhanced by repeated intranasal inoculation. Both types of responses were more marked in pigs inoculated with pathogenic M suipneumoniae than in pigs inoculated with attenuated M suipneumoniae.


Haploid male germ cell- and oocyte-specific Mbd3l1 and Mbd3l2 genes are dispensable for early development, fertility, and zygotic DNA demethylation in the mouse.
Genome-wide erasure of CpG methylation occurs along the paternal pronucleus in fertilized oocytes. This process involves an active, replication-independent enzymatic step, which has remained enigmatic. MBD3L1 and MBD3L2 are two mammalian homologues of the methyl-CpG-binding protein genes MBD2 and MBD3 that arose from recent gene duplication events. Expression of Mbd3l1 occurs specifically in haploid male germ cells. Mbd3l2 expression is restricted to metaphase II oocytes and zygotes making both proteins candidates for the zygotic demethylation process. Neither of these genes was able to promote reactivation of a methylation-silenced reporter gene. We created Mbd3l1 and Mbd3l2 knockout mice, which were viable and fertile. We show that demethylation of the paternal pronucleus in Mbd3l1-/- and Mbd3l2-/- mice is identical to that in wild-type controls. These data suggest that Mbd3l1 and Mbd3l2 are not involved in genome-wide demethylation of paternal genomes in mouse zygotes and are dispensable for normal development.


[Mass spectrometry in the clinical microbiology laboratory].
Infectious diseases are still a cause of high mortality and morbidity rates. Current microbiological diagnostic methods are based on culture and phenotypic identification of isolated microorganisms, which can be obtained in about 24-48 h. Given that the microbiological identification is of major importance for patient management, new diagnostic methods are needed in order to detect and identify microorganisms in a timely and accurate manner. Over the last few years, several molecular techniques based on the amplification of microbial nucleic acids have been developed with the aim of reducing the time needed for the identification of the microorganisms involved in different infectious processes. On the other hand, mass spectrometry has emerged as a rapid and consistent alternative to conventional methods for microorganism identification. This review describes the most widely used mass spectrometry technologies -matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization time-of-flight (ESI-TOF)-, both for protein and nucleic acid analysis, as well as the commercial platforms available. Related publications of most interest in clinical microbiology are also reviewed.


Concurrent validity of single-item measures of emotional exhaustion and depersonalization in burnout assessment.
Burnout is a common problem among physicians and physicians-in-training. The Maslach Burnout Inventory (MBI) is the gold standard for burnout assessment, but the length of this well-validated 22-item instrument can limit its feasibility for survey research. To evaluate the concurrent validity of two questions relative to the full MBI for measuring the association of burnout with published outcomes. DESIGN, PARTICIPANTS, AND MAIN MEASURES: The single questions "I feel burned out from my work" and "I have become more callous toward people since I took this job," representing the emotional exhaustion and depersonalization domains of burnout, respectively, were evaluated in published studies of medical students, internal medicine residents, and practicing surgeons. We compared predictive models for the association of each question, versus the full MBI, using longitudinal data on burnout and suicidality from 2006 and 2007 for 858 medical students at five United States medical schools, cross-sectional data on burnout and serious thoughts of dropping out of medical school from 2007 for 2222 medical students at seven United States medical schools, and cross-sectional data on burnout and unprofessional attitudes and behaviors from 2009 for 2566 medical students at seven United States medical schools. We also assessed results for longitudinal data on burnout and perceived major medical errors from 2003 to 2009 for 321 Mayo Clinic Rochester internal medicine residents and cross-sectional data on burnout and both perceived major medical errors and suicidality from 2008 for 7,905 respondents to a national survey of members of the American College of Surgeons. Point estimates of effect for models based on the single-item measures were uniformly consistent with those reported for models based on the full MBI. The single-item measures of emotional exhaustion and depersonalization exhibited strong associations with each published outcome (all p ≤ 0.008). No conclusion regarding the relationship between burnout and any outcome variable was altered by the use of the single-item measures rather than the full MBI. Relative to the full MBI, single-item measures of emotional exhaustion and depersonalization exhibit strong and consistent associations with key outcomes in medical students, internal medicine residents, and practicing surgeons.


Predicted essential proteins of Plasmodium falciparum for potential drug targets.
To identify novel drug targets for treatment of Plasmodium falciparum. Local BLASTP were used to find the proteins non-homologous to human essential proteins as novel drug targets. Functional domains of novel drug targets were identified by InterPro and Pfam, 3D structures of potential drug targets were predicated by the SWISS-MODEL workspace. Ligands and ligand-binding sites of the proteins were searched by Ef-seek. Three essential proteins were identified that might be considered as potential drug targets. AAN37254.1 belonged to 1-deoxy-D-xylulose 5-phosphate reductoisomerase, CAD50499.1 belonged to chorismate synthase, CAD51220.1 belonged to FAD binging 3 family, but the function of CAD51220.1 was unknown. The 3D structures, ligands and ligand-binding sites of AAN37254.1 and CAD50499.1 were successfully predicated. Two of these potential drug targets are key enzymes in 2-C-methyl-d-erythritol 4-phosphate pathway and shikimate pathway, which are absent in humans, so these two essential proteins are good potential drug targets. The function and 3D structures of CAD50499.1 is still unknown, it still need further study.


Distribution of extracellular and intracellular antibiotic resistance genes in sludge fractionated in terms of settleability.
The widespread proliferation of antibiotic resistance genes (ARGs) is a serious environmental and human health issue. Wastewater treatment facilities (WWTFs) are potential sources to spread ARGs to natural environment, for which, the presence state of ARGs in the sludge, as extracellular ones (eARGs) or intracellular ones (iARGs), along with the sludge settleability, are very important factors. The sludge settleability is closely associated with its floc size and density, bacterial activity, and the proportion of intact/damaged bacterial cells that aggregate together to form flocs for separation in the sedimentation process. It is reasonable to hypothesize that the distribution of eARGs and iARGs may differ with the sludge fractions of different settleability, a topic of great academic and practical significance requiring clarification. In this study, sludge samples from the aerobic contact tank of six household WWTFs were fractionated into fractions with different settling velocities: sludge of low settleability (LS), medium settleability (MS) and high settleability (HS); and the distribution of eARGs and iARGs in the obtained fractions for the widely detected tet G, tet M and sul 1 in water environment was evaluated based on the PMA-qPCR method, together with the evaluation for the well reported mobile genomic element intl 1 and total bacterial 16S rDNA. For the LS fractions, which contained more damaged bacterial cells, the distribution percentages of eARGs were generally higher than those of iARGs. For the HS fractions, which contained flocs with larger sizes formed by both intact and damaged bacterial cells, the relative abundances of ARGs and intl 1 were found apparently lower even if the presence percentages of eARGs were comparatively higher. It is thus inferable that sludge fractions of LS may possess higher transfer potential for ARGs and enhancing their settleability through optimization of the operation conditions is important for mitigating the proliferation of ARGs.


Optimized transformation of Streptomyces sp. ATCC 39366 producing leptomycin by electroporation.
Streptomyces sp. ATCC 39366 produces leptomycin derivatives. Leptomycin B, a potent and specific inhibitor against the export of nuclear proteins, is the main product; however, the introduction of DNA into this strain is almost impossible, which has impeded its further use. We developed a Streptomyces sp. ATCC 39366 transformation protocol to introduce foreign DNA via electroporation. Various conditions were examined, including treatments of the cell wall with weakening agents, electroporation parameters, and DNA content. We found that only plasmid DNA isolated from a dam (-) ET12567 strain resulted in successful transformation. The mycelium growing in a yeast-peptone-dextrose medium supplemented with 1% glycine at 28°C on a rotary shaker (220 rpm) was more dispersed than those without supplementation and prone to electroporation. The maximum transformation efficiency of 8×10(2) CFU/μg plasmid DNA was obtained at a field strength of 13 kV/cm with a time constant of 13 ms (25-μF capacitor; parallel resistance, 600 Ω) using 1-mm electrocuvettes. The results of the transformations of two other Streptomyces species indicated that the optimized conditions established in this study might only be applicable to Streptomyces sp. ATCC 39366. However, this is the first report of successful transformation of Streptomyces sp. ATCC 39366, and will facilitate the construction of a gene knockout mutant in Streptomyces sp. ATCC 39366 to produce series of new leptomycin derivatives.


Fecal microbiota transplantation research output from 2004 to 2017: a bibliometric analysis.
Fecal microbiota transplantation (FMT) is an emerging therapy against Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although the therapy has gained prominence, there has been no bibliometric analysis of FMT. Studies published from 2004 to 2017 were extracted from the Science Citation Index Expanded. Bibliometric analysis was used to evaluate the number or cooperation network of publications, countries, citations, references, journals, authors, institutions and keywords. A total of 796 items were included, showing an increasing trend annually. Publications mainly came from 10 countries, led by the US (n = 363). In the top 100 articles ranked by the number of citations (range 47-1,158), American Journal of Gastroenterology (2017 IF = 10.231) took the top spot. The co-citation network had 7 co-citation clusters headed by 'recurrent Clostridium difficile infection'. The top 7 keywords with the strongest citation bursts had three parts, 'microbiota', ' diarrhea ', and 'case series'. All keywords were divided into four domains, 'disease', 'nosogenesis', 'trial', and 'therapy'. This study shows the research performance of FMT from 2004 to 2017 and helps investigators master the trend of FMT, which is also an ongoing hotspot of research.


The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old--Taiwan's PPV vaccination program.
Pneumococcal infection is a serious cause of mortality and morbidity in the elderly. A nationwide pneumococcal polysaccharide vaccine (PPV) program for elderly adults aged 75 years and older was conducted in Taiwan in 2008. The efficacy of the PPV in this very elderly population was evaluated. The data were analyzed using the Taiwan National Health Insurance Research Database (NHIRD), the cause-of-death registration database and the invasive pneumococcal disease (IPD) notification database of Taiwan's Ministry of Health and Welfare. The efficacy of PPV administration in this very elderly population was evaluated using multivariate logistic regression after propensity score matching (PSM). The rates of IPD, death from IPD, pneumonia hospitalization, death from pneumonia, and all-cause mortality were compared for those who did and did not receive the PPV. Among the 1078,955 eligible people, 318,257 (29.5%) received the PPV, and 760,698 (70.5%) were not vaccinated. Using PSM to adjust for confounding factors, including age, gender, influenza vaccination status, associated chronic diseases and health care utilization, those who received the PPV had significantly lower odds ratios (ORs) for IPD (OR=0.24, 95% CI=0.123-0.461, p<0.001), death from IPD (OR=0.09, 95% CI=0.011-0.704, p<0.022, p<0.001), pneumonia hospitalization (OR=0.40, 95% CI=0.395-0.415, p<0.001), death from pneumonia (OR=0.07, 95% CI=0.059-0.082, p<0.001), and all-cause mortality (OR=0.07, 95% CI=0.069-0.072, p<0.001) compared with those who were not vaccinated. PPV vaccination in the previous year was associated with a 60% reduction in pneumonia hospitalization, a 76% reduction in IPD, and a greater than 90% reduction in death from pneumonia, IPD and all causes among people over 75 years old in Taiwan. Data from subsequent years in Taiwan and similar populations elsewhere are needed to evaluate the contribution of underlying variations in the mortality rate and the confounding effects of prior disease severity to these findings.


Childhood lower respiratory tract infections linked to residential airborne bacterial and fungal microbiota.
Residential microbial composition likely contributes to the development of lower respiratory tract infections (LRTI) among children, but the association is poorly understood. We aimed to study the relationship between the indoor airborne dust bacterial and fungal microbiota and childhood LRTI in Ibadan, Nigeria. Ninety-eight children under the age of five years hospitalized with LRTI were recruited and matched by age (±3 months), sex, and geographical location to 99 community-based controls without LRTI. Participants' homes were visited and sampled over a 14-day period for airborne house dust using electrostatic dustfall collectors (EDC). In airborne dust samples, the composition of bacterial and fungal communities was characterized by a meta-barcoding approach using amplicons targeting simultaneously the bacterial 16S rRNA gene and the internal-transcribed-spacer (ITS) region-1 of fungi in association with the SILVA and UNITE database respectively. A 100-unit change in house dust bacterial, but not fungal, richness (OR 1.06; 95%CI 1.03-1.10) and a 1-unit change in Shannon diversity (OR 1.92; 95%CI 1.28-3.01) were both independently associated with childhood LRTI after adjusting for other indoor environmental risk factors. Beta-diversity analysis showed that bacterial (PERMANOVA p < 0.001, R2 = 0.036) and fungal (PERMANOVA p < 0.001, R2 = 0.028) community composition differed significantly between homes of cases and controls. Pair-wise differential abundance analysis using both DESEq2 and MaAsLin2 consistently identified the bacterial phyla Deinococcota (Benjamini-Hochberg (BH) adjusted p-value <0.001) and Bacteriodota (BH-adjusted p-value = 0.004) to be negatively associated with LRTI. Within the fungal microbiota, phylum Ascomycota abundance (BH adjusted p-value <0.001) was observed to be directly associated with LRTI, while Basidiomycota abundance (BH adjusted p-value <0.001) was negatively associated with LRTI. Our study suggests that early-life exposure to certain airborne bacterial and fungal communities is associated with LRTI among children under the age of five years.


Mitofusins, from Mitochondria to Metabolism.
Mitochondrial architecture is involved in several functions crucial for cell viability, proliferation, senescence, and signaling. In particular, mitochondrial dynamics, through the balance between fusion and fission events, represents a central mechanism for bioenergetic adaptation to metabolic needs of the cell. As key regulators of mitochondrial dynamics, the fusogenic mitofusins have recently been linked to mitochondrial biogenesis and respiratory functions, impacting on cell fate and organism homeostasis. Here we review the implication of mitofusins in the regulation of mitochondrial metabolism, and their consequence on energy homeostasis at the cellular and physiological level, highlighting their crucial role in metabolic disorders, cancer, and aging.


Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line.
The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2-ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCaP genomic DNA and observed a massive number of genomic rearrangements along the q arm of chromosome 5, characteristic of chromothripsis. Chromothripsis is a recently recognized phenomenon characterized by extensive chromosomal shattering in a single catastrophic event, mainly detected in cancer cells. Various structural events identified on chromosome 5q of VCaP resulted in gene fusions. Out of the 18 gene fusion candidates tested, 15 were confirmed on genomic level. In our set of gene fusions, only rarely we observe microhomology flanking the breakpoints. On RNA level, only five transcripts were detected and NDUFAF2-MAST4 was the only resulting in an in-frame fusion transcript. Our data indicate that although a marker of genomic instability, chromothripsis might lead to only a limited number of functionally relevant fusion genes.


[Histamine stimulates thermogenesis of brown and beige fat].
β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.


Particulate matter assessment of a wetland in Beijing.
To increase the knowledge on the particulate matter of a wetland in Beijing, an experimental study on the concentration and composition of PM10 and PM2.5 was implemented in Beijing Olympic Forest Park from 2013 to 2014. This study analyzed the meteorological factors and deposition fluxes at different heights and in different periods in the wetlands. The results showed that the mean mass concentrations of PM10 and PM2.5 were the highest at 06:00-09:00 and the lowest at 15:00-18:00. And the annual concentration of PM10 and PM2.5 in the wetland followed the order of dry period (winter)>normal water period (spring and autumn)>wet period (summer), with the concentration in the dry period significantly higher than that in the normal water and wet periods. The chemical composition of PM2.5 in the wetlands included NH4(+), K(+), Na(+), Mg(2+), SO4(2-), NO3(-), and Cl(-), which respectively accounted for 12.7%, 1.0%, 0.8%, 0.7%, 46.6%, 33.2%, and 5.1% of the average annual composition. The concentration of PM10 and PM2.5 in the wetlands had a significant positive correlation with relative humidity, a negative correlation with wind speed, and an insignificant negative correlation with temperature and radiation. The daily average dry deposition amount of PM10 in the different periods followed the order of dry period>normal water period>wet period, and the daily average dry deposition amount of PM2.5 in the different periods was dry period>wet period>normal water period.


Potent Inhibitory Effect of Chinese Dietary Spices on Fatty Acid Synthase.
Dietary spices have been adopted in cooking since ancient times to enhance flavor and also as food preservatives and disease remedies. In China, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their functions. Fatty acid synthase (FAS) has been recognized as a remedy target, and its inhibitors might be applied in disease treatment. The present work was designed to assess the inhibitory activities on FAS of spices extracts in Chinese menu. The in vitro inhibitory activities on FAS of 22 extracts of spices were assessed by spectrophotometrically monitoring oxidation of NADPH at 340 nm. Results showed that 20 spices extracts (90.9 %) exhibited inhibitory activities on FAS, with half inhibition concentration (IC(50)) values ranging from 1.72 to 810.7 μg/ml. Among them, seven spices showed strong inhibitory effect with IC(50) values lower than 10 μg/ml. These findings suggest that a large proportion of the dietary spices studied possess promising inhibitory activities on FAS, and subsequently might be applied in the treatment of obesity and obesity-related human diseases.


Electromyographic findings in primary lateral sclerosis during disease progression.
To characterize electromyographic (EMG) findings in patients with primary lateral sclerosis (PLS) during the disease course. In PLS patients we scored spontaneous activity and motor unit action potential (MUP) pattern on EMG. We compared patients according to lower (group A) and higher (group B) EMG scores. EMG studies were repeated at intervals longer than 11 months; two or three repeat studies were required for inclusion in the analysis. We studied 22 patients. Fasciculation potentials were found in 13 and fibrillations/positive sharp waves (fibs/sw) in 3 patients. Both were stable over time. Most patients had MUP abnormalities (n = 17), with worsening in the lower limbs in patients with three evaluations (p = 0.010). Compared to group A (n = 12), patients of group B (n = 10) had a significant shorter disease duration (median 10.9 vs 15.2 years, p < 0.001), lower functional score at both first (39 vs 45, p = 0.034) and last (29 vs 38, p = 0.003) evaluations, and had a faster functional decline (0.19 vs 0.08, p = 0.004). Most PLS patients showed minor and stable EMG abnormalities, without progression to ALS. Patients with more EMG abnormalities have a faster progression. EMG abnormalities in most PLS patients are minor and stable.


Development and validation of a standardized ELISA for the detection of soluble Fc-epsilon-RI in human serum.
The aim of this study was to develop a standardized enzyme-linked immunosorbent assay (ELISA) for detection of human soluble Fc-epsilon-RI (sFcεRI), a serum isoform of the high affinity IgE receptor. A recombinant version of sFcεRI was produced in baculovirus and used as standard. ELISA plates were coated with anti-mouse IgG followed by incubation with the monoclonal capture antibody CRA1. This FcεRI-alpha-specific antibody binds to the stalk region of the protein and does not inhibit IgE-binding. After incubation with standards or serum samples, plates were incubated with chimeric IgE followed by detection with horseradish peroxidase conjugated anti-human IgE. Enzymatic activity was visualized with (3,3',5,5')-tetramethylbenzidine. Specificity was demonstrated by omission of capture or detection reagents. Units (U) of detection were established and the dynamic range of the assay was defined as 10-640 U/ml for a 1/5 serum dilution. Parameters of linearity (R(2)>0.999), matrix interference test (recovery of 70-110%), intra-assay variability (coefficient of variation (CV) <20%) and inter-assay variability (CV <20%) met acceptance criteria for immunoassay validation. Correlation analysis of serum units of sFcεRI measured with the new ELISA and serum IgE levels confirmed earlier published data describing a weak correlation of the two parameters in patients with elevated serum IgE while no correlation in patients with normal serum IgE or the total patient group was found. In summary, we established and validated a standardized ELISA for the detection of sFcεRI. This novel method now allows for comparative analysis of sFcεRI levels in health and disease.


MiR-200a Suppresses the Proliferation and Metastasis in Pancreatic Ductal Adenocarcinoma through Downregulation of DEK Gene.
MiR-200a has been reported to be able to suppress the epithelial-mesenchymal transition process in pancreatic cancer stem cells, suggesting that miR-200a could suppress the metastasis of pancreatic ductal adenocarcinoma (PDAC). However, its role in proliferation and metastasis of PDAC and the underlying mechanism by which miR-200a works in PDAC have not been elucidated. In our study, we for the first time identified that DEK gene is a direct downstream target of miR-200a. It was found that overexpression of miR-200a decreased DEK expression, suppressing the proliferation, migration, and invasion of PDAC cells. Meanwhile, knockdown of miR-200a can increase DEK level, promoting the proliferation, migration, and invasion of PDAC cells. Our study demonstrated that miR-200a suppresses the metastasis in pancreatic PDAC through downregulation of DEK, suggesting that miR-200a may be used as a novel potential marker in prediction of metastasis of PDAC.


Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population.
The mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) is deficient in Alzheimer's disease (AD). The DLST gene encodes the core, dihydrolipoyl succinyltransferase (DLST) component of KGDHC, and recent reports indicate an association between polymorphisms of DLST and AD in both white and Japanese patients. We therefore examined the relationship between AD and the DLST and apolipoprotein E (APOE) genes in elderly (89 +/- 7 years) AD patients, in whom the epsilon4 allele of APOE (APOE4) is a weak risk factor for AD. Polymorphisms of DLST (A19,117G and T19,183C), shown to be of interest in previous studies, were analyzed by restriction fragment length polymorphism analysis after polymerase chain reaction amplification. In a series of 429 white subjects from two Jewish nursing homes, an association of APOE4 with AD was found only in patients homozygous for the G,C allele of DLST. Similar relationships occurred in the "very elderly" (> or =85 years, n = 302) subgroup of this series, and also in an autopsy series (n = 225) that included white subjects from the Jewish nursing homes as well as other white subjects. These findings suggest a relationship between APOE4 and a DLST locus in the pathogenesis of AD in very elderly subjects.


Psychometric differentiation of psychogenic and organic erectile disorders.
A study was conducted to assess the discriminant validity of patient responses to a questionnaire in distinguishing between organic and psychogenic erectile dysfunction. A total of 56 urologist-referred veterans slept for 3 nights in a sleep laboratory for nocturnal penile tumescence recording. Based on nocturnal penile tumescence results 48 patients were assigned to an organic group and the remaining 8 were assigned to a psychogenic group. A discriminant function analysis of questionnaire responses yielded a highly significant discriminant function [chi-square (19) equals 63.88, p less than 10(-6)], and all 56 patients were classified correctly into the nocturnal penile tumescence-defined organic and psychogenic groups. It was concluded that verbally reported data contain diagnostically meaningful information and that such information can compare favorably with information collected through standard laboratory-based nocturnal penile tumescence techniques.


Mass spectrometry-based analysis of glycoproteins and its clinical applications in cancer biomarker discovery.
Glycosylation is one of the most important posttranslational modifications of proteins and plays essential roles in various biological processes. Aberration in the glycan moieties of glycoproteins is associated with many diseases. It is especially critical to develop the rapid and sensitive methods for analysis of aberrant glycoproteins associated with diseases. Mass spectrometry (MS) has become a powerful tool for glycoprotein analysis. Especially, tandem mass spectrometry can provide highly informative fragments for structural identification of glycoproteins. This review provides an overview of the development of MS technologies and their applications in identification of abnormal glycoproteins and glycans in human serum to screen cancer biomarkers in recent years.


[Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery].
The renal cell tumour supposes 1% of the adult's tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish.


Do survivors respond differently when alcohol abuse complicates suicide? Findings from the psychological autopsy study in Estonia.
When a person with alcohol use disorder commits suicide, do the immediate family members (parents, spouses, and children) react differently from the relatives of non-alcohol-related suicides? From a series of 427 psychological autopsies conducted in Estonia we selected 261 cases of suicide where the key informants were close relatives. Of the 261 suicides, 148 met the DSM-IV criteria for alcohol use disorder (alcohol abuse and alcohol dependence), while 113 did not. Unconditional logistic regression was used to estimate the association in terms of emotions. The spouses of alcohol misusing suicides were significantly more likely to react with anger than those when alcohol did not complicate the picture (adjusted OR=3.8, 95% CI=1.4-0.4). The children of persons with alcohol use disorder, who committed suicide were less likely to feel guilty (adjusted OR=0.2, 95% CI=0.1-0.8) or abandoned (adjusted OR=0.2, 95% CI=0.1-0.7) than children of non-alcohol-related suicide victims. There were no statistically significant differences in surviving parents' emotions. Alcohol use disorder before suicide changes affective responses in spouses and children who are left behind. Bereavement counsellors should be alert for complex grief and mourning responses among this group of suicide survivors.


PhotoSENSIL-18 assay development: Enhancing the safety testing of cosmetic raw materials and finished products to support the in vitro photosensitization assessment?
Although photosensitization remains a major toxicological endpoint for the safety assessment of cosmetic products and their raw materials, there is no validated in vitro method available for the evaluation of this adverse effect so far. Given that previous studies have proposed that the Interleukine-18 (IL-18) plays a key role in keratinocyte-driven pro-inflammatory responses specific of the skin sensitization process, we hypothesize that IL-18 might be used as a specific biomarker for in vitro photosensitization assessment. The aim of the present study was the set-up of a new in vitro assay using IL-18 as a biomarker for the identification of photosensitizers in a reconstructed human epidermis (RHE) model. EpiCS™ RHE were incubated with a set of 16 known sensitising / phototoxic / photosensitizing substances and exposed to ultra-violet (UV) irradiation. Then, the cell viability was analysed by MTT assay, while the IL-18 secretion was quantified by ELISA. Preliminary assays have shown that 1 h of incubation followed by a recovery period of 23 h induced the highest IL-18 production in response to UV exposure. This protocol was used to test 16 substances and a ratio of IL-18 production (UV+/UV- ratio) was then generated. Our data shows that the cut-off of 1.5 (UV+/UV- ratio) is the most predictive model among the tested conditions, being capable of identifying true positive photosensitizers (8 of 9) with a good prediction in comparison with in vivo data. In a nutshell, our data suggests that the PhotoSENSIL-18 is a promising in vitro method for identification of photosensitizing substances. Although further studies are necessary to optimize the model, we foresee that the PhotoSENSIL-18 assay can be used in the context of an Integrative Approach to Testing and Assessment (IATA) of chemicals.


SNAPPE-II and MDAS scores as predictors for surgical intervention in very low birth weight neonates with necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency in preterm and term neonates, with the majority of cases affecting neonates classified as very low birth weight (VLBW, bw <1500 g). Scores for neonatal acute physiology-perinatal extension-II (SNAPPE-II) and metabolic derangement acuity score (MDAS) have been developed and utilized to assess neonatal morbidity and mortality including the subset of VLBW neonates. Serial SNAPPE-II and MDAS scores have been reported in neonates with necrotizing enterocolitis to assist in surgical management, yielding mixed results. To determine the relationship between clinical and/or laboratory deterioration using SNAPPE-II and MDAS scores measured at the time of NEC diagnosis and surgical management of NEC. We retrospectively evaluated preterm neonates ≥23 weeks gestational age who developed pneumatosis intestinalis on radiographic imaging coupled with clinical signs of NEC. SNAPPE-II and MDAS scores were calculated within twelve hours of birth and within twelve hours of initial finding of pneumatosis intestinalis. Baseline characteristics and clinical variables between those who did and did not require surgical intervention were compared. Logistic regression and receiver - operator characteristics (ROC) curve analyses were also performed, and areas under the curve (AUC) computed, to assess the performance of SNAPPE-II and MDAS scoring systems to differentiate neonates with NEC in the two groups. Sixty-four neonates were evaluated in our study of which 20 required surgical management of NEC. While the baseline SNAPPE-II and MDAS scores did not differ between the surgical management and medical management only groups, when rescored within 12 h of NEC diagnosis, the surgical management group had significantly higher SNAPPE -II (38 (18.5-69) vs. 19 (10-34.5), p = .04) and MDAS (2.5 (1-3) vs. 1 (0-2), p = .0004) scores. The AUCs for MDAS 0.77 (95% CI 0.65-0.89 and 0.71 (95% CI 0.57-0.85) for SNAPPE-II, indicating an acceptable level of diagnostic ability of both scoring systems to differentiate between those who did and did not need surgical management. SNAPPE II and MDAS scores performed within 12 h of NEC diagnosis may be useful in predicting which preterm VLBW neonates will require surgical intervention.


Development of a loop-mediated isothermal amplification assay targeting the mpb64 gene for diagnosis of intraocular tuberculosis.
A loop-mediated isothermal amplification (LAMP) assay targeting the mpb64 gene for the diagnosis of intraocular tuberculosis was highly specific (100%), sensitive (85.7%), rapid, and easy to perform. The LAMP assay can be an alternative to conventional PCR for the diagnosis of ocular tuberculosis in resource-limited settings.


Research and application of leek roots in medicinal field.
Some Chinese herbs have been used to prevent and treat diseases, and are also used as common food ingredients. These Chinese herbs are potential resource for research and development of new drugs. Leek roots is a typical medicine of food and medicine continuum. It has a long history of medicinal applications and edible food in China. In this paper, the origin, biological active components, pharmacological action and clinical application of leek roots were introduced. We hope that this review will contribute to the development of leek roots for pharmaceutical research and clinical applications, as well as related health products.


Dry-reagent disposable biosensor for visual genotyping of single nucleotide polymorphisms by oligonucleotide ligation reaction: application to pharmacogenetic analysis.
Most genotyping methods for known single-nucleotide polymorphisms (SNPs) are based on hybridization with allele-specific probes, oligonucleotide ligation reaction (OLR), primer extension or invasive cleavage. OLR offers superior specificity because it involves two recognition events; namely, the hybridization of an allele-specific probe and a common probe to adjacent positions on target DNA. OLR products can be detected by microtiter well-based colorimetric, time-resolved fluorimetric or chemiluminometric assays, electrophoresis, microarrays, microspheres, and homogeneous fluorimetric or colorimetric assays. We have developed a simple, robust, and low-cost disposable biosensor in dry-reagent format, which allows visual genotyping with no need for instrumentation. The OLR mixture contains a biotinylated common probe and an allele-specific probe with a (dA)(20) segment at the 3'-end. OLR products are denatured and applied to the biosensor next to gold nanoparticles that are decorated with oligo(dT) strands. The sensor is immersed in the appropriate buffer and all components migrate by capillary action. The OLR product is captured by immobilized streptavidin at the test zone (TZ) of the sensor and hybridizes with the oligo(dT) strands of the nanoparticles. A characteristic red line is generated due to the accumulation of nanoparticles. The excess nanoparticles are captured by immobilized oligo(dA) at the control zone of the strip, giving a second red line. We have applied successfully the proposed OLR-dipstick assay to the genotyping of four SNPs in the drug-metabolizing enzyme genes CYP2D6 ((*)3 and (*)4) and CYP2C19 ((*)2 and (*)3). The results were in agreement with direct sequencing.


Epigenetic changes in headache.
Multiple factors, including both genetic and environmental mechanisms, appear to play a role in the aetiology of headache. An interesting area of study is the possible involvement of epigenetic mechanisms in headache development and the transformation to chronic headache, and the potential role of these factors as a therapeutic target. We performed a literature review of the involvement of different epigenetic mechanisms in headache, mainly using the Medline/PubMed database. To this end, we used the following English search terms: headache, migraine, epigenetics, DNA methylation, histones, non-coding RNA, and miRNA. A total of 15 English-language publications related to the above terms were obtained. There is limited but consistent evidence of the relationship between epigenetics and headache; it is therefore essential to continue research of epigenetic changes in headache. This may help to understand the pathophysiology of headache and even to identify candidate biomarkers and new, more effective, therapeutic targets.


Blunt bladder trauma: manifestation of severe injury.
Twenty-nine patients with bladder injuries requiring operative treatment as a result of blunt trauma are presented. Motor vehicle accidents accounted for 86 per cent of the injuries. Hypotension and gross hematuria were the most prevalent clinical features, 68 per cent and 97 per cent, respectively. All patients had multiple associated injuries requiring operative treatment, average 2.9 per patient. Pelvic fractures occurred in 93 per cent and intra-abdominal injuries in 48 per cent of patients. The majority of ruptures (72%) were intraperitoneal. Mortality, related to associated injuries, was high (34%), attesting to the magnitude of injury sustained by the victim.


The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium.
Despite high rates of cell death, epithelia maintain intact barriers by squeezing dying cells out using a process termed cell extrusion. Cells can extrude apically into the lumen or basally into the tissue the epithelium encases, depending on whether actin and myosin contract at the cell base or apex, respectively. We previously found that microtubules in cells surrounding a dying cell target p115 RhoGEF to the actin cortex to control where contraction occurs. However, what controls microtubule targeting to the cortex and whether the dying cell also controls the extrusion direction were unclear. Here we find that the tumor suppressor adenomatous polyposis coli (APC) controls microtubule targeting to the cell base to drive apical extrusion. Whereas wild-type cells preferentially extrude apically, cells lacking APC or expressing an oncogenic APC mutation extrude predominantly basally in cultured monolayers and zebrafish epidermis. Thus APC is essential for driving extrusion apically. Surprisingly, although APC controls microtubule reorientation and attachment to the actin cortex in cells surrounding the dying cell, it does so by controlling actin and microtubules within the dying cell. APC disruptions that are common in colon and breast cancer may promote basal extrusion of tumor cells, which could enable their exit and subsequent migration.


CCN1 suppresses cell proliferation of esophageal squamous cell carcinoma through amyloid precursor protein without DR6 participation.
Esophageal cancer is commonly seen as either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC), two very different cancers. CCN1 is a matricellular protein that induces apoptosis in EAC cells through upregulation of DR5, a death receptor, while its role in ESCC is unclear. DR6 is another death receptor, which has been reported to induce apoptosis, necroptosis, or pyroptosis in various cell systems with or without the engagement of its putative ligand amyloid precursor protein (APP). In this study, we found that CCN1 and DR6 were both highly expressed in ESCC but downregulated in EAC. Overexpression of CCN1 in ESCC cells inhibited cell proliferation through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not affect cell growth or cell death whatsoever.


Difference in periprosthetic acetabular bone mineral density: Prior total hip arthroplasty: Osteonecrosis of the femoral head versus primary osteoarthritis.
Total hip arthroplasty (THA) could be associated with a higher failure rate in patients after osteonecrosis of the femoral head (ONFH) compared to a patient population with primary osteoarthritis prior THA, especially regarding the acetabular component. One major reason could be the compromised acetabular bone quality. Therefore, we performed a retrospective case matched study to assess: 1) Is there a difference in periprosthetic bone mineral density between patients with an ONFH prior THA and controls? 2) Do patients with an ONFH prior THA have a lower bone mineral density compared to controls? 3) Which region in the periprosthetic bone stock is more likely to present differences in periprosthetic bone mineral density between both groups? We hypothesized that there is a poorer bone mineral density (BMD) in the periacetabular bone stock in patients with an ONFH prior THA compared to controls receiving a THA due to primary osteoarthritis. We compared the BMD of 50 patients with ONFH to 50 controls with primary osteoarthritis prior THA using the same implant in mean 5 years after surgery by means of dual energy X-ray absorptiometry (DXA). We analysed 3 acetabular ROIs according to DeLee and Charnley in a modified measurement technique. In ROI 3, representing acetabulum's upper aspect, statistically significant lower BMD values for the ONFH group could be found (P < 0.05). No difference was found for the modified ROIs 1 and 2 (respectively medial and lower acetabulum). The results indicate a poorer periacetabular BMD in patients with ONFH prior THA, which might be responsible for premature loosening of the acetabular cup in THA. Due to a lack of literature, further clinical investigations are required to confirm our results. III: retrospective case-control study.


Metabolic response to hypertonic glucose administration in Reye syndrome.
Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.


[Carcinoma in situ of the bladder. Apropos of 10 cases].
10 cases of primary carcinoma in situ are described and the symptomatology of the disease is analysed. The role of cytodiagnosis is emphasised. The evolution is variable. In 2 cases the bladder became totally retracted and total cystectomy had to be performed in spite of the fact that the lesion remained intra-urothelial. Invasive cancer developped only in 2 cases: 7 and 6 years after diagnosis. Conservative treatment by Tur seems logical whilst the carcinoma remains strictly "in situ".


The use of inhaled glucocorticosteroids and recovery from adrenal suppression after systemic steroid use in a VLBW premature infant with BPD: case report and literature discussion.
Despite development of many prevention and treatment modalities for bronchopulmonary dysplasia (BPD), a form of chronic respiratory insufficiency in premature infants recovering from respiratory distress syndrome, BPD remains a treatment challenge and a significant cause of long-term morbidity. A ventilator-dependent very low birth weight infant in our newborn special care unit was receiving multiple courses of systemic dexamethasone for severe respiratory failure. The infant demonstrated adrenal suppression manifested by a baseline cortisol concentration below reported levels in infants of similar birth weight and postnatal age. We hypothesized that he had developed adrenal insufficiency as a result of the prolonged systemic steroid administration used to treat his respiratory problems. We further hypothesized that inhaled beclomethasone therapy would aid in the infant's recovery phase during relative adrenal insufficiency--and so substituted inhaled for systemic steroids. Inhaled corticosteroid treatment improved the clinical respiratory course and postnatal growth of this premature infant with BPD without inhibiting his recovery from adrenal insufficiency.


Low molecular weight heparins: current use and indications.
Thromboembolic complications are associated with significant morbidity and mortality in postoperative patients. For many years, unfractionated heparin has been used successfully in primary and secondary prophylaxis of these complications. In recent times, however, the usefulness of LMWHs has caught the attention of clinicians because of improved bioavailability, predictable anticoagulation, ease of administration, and the lack of need for monitoring anticoagulation. In clinical situations, LMWHs have been tested and proved to be safe and equipotent or supe rior when compared with unfractionated heparin or warfarin (Table 5). It is clear from clinical trials that LMWHs are superior in primary prophylaxis of DVT in orthopaedic surgical procedures, treatment of unstable angina, and in patients with multiple traumas. LMWHs were also tested and found to be an acceptable alternative to unfractionated heparin in both the primary prophylaxis of DVT in high risk general surgical procedures and in the treatment of patients with DVT and pulmonary embolism. However, the role of LMWHs in ischemic heart diseases, valvular heart diseases, postcoronary angioplasty, and vascular surgery remains to be proved. The major impact of LMWHs would be in allowing clinicians to treat PE and DVT in an outpatient setting, which would directly impact medical economics. LMWHs are associated with similar complications as unfractionated heparin is, but the complications occur less frequently. Currently, the main limitation in using LMWHs in place of unfractionated heparin or warfarin is its cost. However, taking into account the cost incurred by hospitalization and longterm monitoring of anticoagulation in patients treated with unfractionated heparin, certain trials have proved the cost of LMWHs to be the same or less than the cost of unfractionated heparin overall. We envision that LMWHs will be widely used in the future and will bring welcomed change in the treatment of thromboembolic diseases.


Differential effects of localized lesions of n. accumbens on morphine- and amphetamine-induced locomotor hyperactivity in the C57BL/6J mouse.
Mice of the C57BL/6J strain became hyperactive to increasing doses of morphine sulfate. This response was similar to locomotor hyperactivity induced by amphetamine. Lesions and chemical blockade of posterior n. accumbens abolished amphetamine-induced hyperactivity and reduced but did not abolish the morphine response. These experiments demonstrate that the response to the two drugs is mediated by overlapping but noncongruent neural systems.


Forty-Year Survival of Simultaneous Kidney and Duct-Injected Segmental Pancreas Transplants in a Recipient Maintained on Low-Dose Azathioprine and Prednisone.
Here, we report on the remarkable survival of a simultaneous kidney-pancreas transplant recipient who has received minimal immunosuppression, has had normal kidney function, and has been insulin-free for 40 years since her transplant surgery.


[Unilateral exophthalmos and temporary ipsilateral oculomotor paresis and the only symptoms of an extensive chordoma of the base of the skull (author's transl)].
A case of histologically proved chordoma of the region of the base of the skull in an 18-year-old girl is described. In spite of great extension of the tumor from the clivus into the nasopharynx only a unilateral protrusio bulbi was apparent. The patient was treated with high-dose radiotherapy. Continual half-yearly follow-ups showed during 3 1/2 years no progression of the process.


The prosthodontic rehabilitation of malpositioned implants in a patient with basal cell carcinoma: a clinical report.
This clinical report describes the prosthodontic rehabilitation of a patient with a partially edentulous maxilla and compromised mandibular anatomy caused by resection of bone due to basal cell carcinoma. Placement of a fibula bone graft was followed by placement of 2 implants. The implants were malpositioned in the anteroposterior plane due to the altered form of the alveolar bone. Prosthodontic treatment included a maxillary removable partial denture and a mandibular partial overdenture supported by implants and remaining teeth.


Frequency distribution of sperm counts in fertile and infertile males.
In this study the frequency distribution of sperm counts and total sperm counts from more than 4000 allegedly fertile males were compared with those of husbands in 1000 infertile couples. Significant differences were observed only at the lower end of the scale (sperm counts below 10 million/ml and total sperm counts below 25 million/ejaculate). Frequency distributions of sperm counts above 10 million/ml or total sperm counts above 25 million/ejaculate revealed little difference between the fertile and infertile groups. These data suggest that, unless other parameters are found to be abnormal, sperm counts and total sperm counts above 10 million/ml and 25 million/ejaculate, respectively, probably are not major factors in a couple's infertility.


Binding thermodynamics of serotonin to rat-brain 5-HT1A, 5HT2A and 5-HT3 receptors.
The thermodynamic parameters delta G degrees, delta H degrees and delta S degrees of the binding equilibrium of serotonin to 5-HT1A, 5-HT2A and 5-HT3 rat-brain membrane receptors have been determined by means of affinity constant measurements at six temperatures in the range 0 -35 degrees C and van't Hoff plots. At variance with 5-HT1A and 5-HT3, the binding at the 5-HT2A receptors is strongly endothermic and entropy-driven. Comparison with the results obtained by other authors on 5-HT2A receptors in rats and humans suggests that the observed differences can be explained by a single amino acid difference in the receptor sequence between these two species.


The very many faces of presenilins and the γ-secretase complex.
Presenilin is a central, catalytic component of the γ-secretase complex which conducts intramembrane cleavage of various protein substrates. Although identified and mainly studied through its role in the development of amyloid plaques in Alzheimer disease, γ-secretase has many other important functions. The complex seems to be evolutionary conserved throughout the Metazoa, but recent findings in plants and Dictyostelium discoideum as well as in archeons suggest that its evolution and functions might be much more diversified than previously expected. In this review, a selective survey of the multitude of functions of presenilins and the γ-secretase complex is presented. Following a brief overview of γ-secretase structure, assembly and maturation, three functional aspects are analyzed: (1) the role of γ-secretase in autophagy and phagocytosis; (2) involvement of the complex in signaling related to endocytosis; and (3) control of calcium fluxes by presenilins.


Minimal Residual Disease Monitoring in Adult ALL to Determine Therapy.
Almost 90 % of children and 50 % of adults with acute lymphoblastic leukemia (ALL) are cured by modern treatment regimens, with significant variations due to several disease- and host-related characteristics. The attainment of an early remission and the avoidance of relapse and treatment-related mortality are the fundamental therapeutic steps. In remission patients, the assessment of the disease response to early intensive therapy through the detection and monitoring of minimal residual disease (MRD) can accurately refine the individual prognosis and is increasingly used to support a risk-oriented treatment strategy. In this way, only the patients with an unfavorable MRD response are preferably selected for allogeneic stem cell transplantation, irrespective of their clinical risk class. This choice spares transplant-related toxicities to MRD responsive cases. Further advancement is expected by integrating the MRD analysis with improved pediatric-type regimens and novel targeting agents for ALL subsets at higher risk of relapse.


Minimal lift-multiple rotation technique for capsular bag phacoemulsification and intraocular lens fixation.
A method of capsular bag phacoemulsification is outlined step-by-step. The surgical technique has proven safe and efficient and preserves the architecture of the capsular bag for hard or soft intraocular lens implantation. It represents a practical, modern method for cataract extraction and intraocular lens implantation.


Intracranial mass lesions associated with late-onset psychosis and depression.
Tumors and other mass lesions of the brain may present with symptoms resembling psychosis or depression or with features of delusions, hallucinations, mania, or catatonia. There is an over-representation of tumors affecting the frontal lobe, temporal lobe, and diencephalon in patients with these manifestations. Neurologic symptoms and signs may be helpful in making an early diagnosis of the tumor. Patients with late-onset psychosis, unusual histories of depression, and those with focal neurologic findings associated with psychotic disorders should undergo computerized tomographic (CT) scanning to exclude a focal brain lesion.


Reusable flexible poly(vinyl alcohol)/chitosan-based polymer carbon dots composite film for acid blue 93 dye adsorption.
The design and synthesis of water-insoluble chitosan-based polymer carbon dots [P(CS-g-CA)CDs] are described. A polyvinyl alcohol/chitosan-based polymer carbon dot [PVA/P(CS-g-CA)CDs] composite film was prepared using a simple casting method to be used in dye adsorption. The composite film was characterized using FT-IR, XPS, transparency, contact angle, and mechanical properties tests, which showed the successful incorporation of P(CS-g-CA)CDs into the film and also revealed that hydrogen bonding improved the mechanical properties of the PVA film. Furthermore, the composite film displayed substantially enhanced hydrophobicity, making it suitable for use in aqueous environments. In addition, the composite film exhibited stable adsorption of acid blue 93 (AB93) at pH 2-9, with an enhanced adsorption capacity of 433.24 mg/g. The adsorption obeyed Langmuir law with an efficiency of more than 89% even after five cycles. Therefore, the PVA/P(CS-g-CA)CDs film is a promising material for the treatment of organic dye-polluted wastewater.


Immunomodulatory activity of recombinant IL-1 receptor (IL-1-R) on models of experimental rheumatoid arthritis.
Given the role of IL-1 in inflammation and in autoimmune diseases, studies were designed to examine the ability of IL-1 receptor (IL-1-R) to suppress inflammation in a model of chronic degenerative joint disease of adjuvant arthritis (AA) in Lewis rats and to suppress the development of a systemic lupus erythematosus (SLE)-like disease in MRL/lpr mice. IL-1-R was able to prevent the onset of the AA and, even if therapy started after the establishment of AA, the cytokine receptor was still able to reduce the degree of chronic inflammation and arrested its progress. Treating MRL/lpr mice with IL-1-R resulted in a decrease in the amount of autoantibodies and inhibited joint inflammation. Even in the established disease IL-1-R could reduce rheumatoid factors (RF) and autoantibodies, and the signs of a polyarthritis were inhibited.


Effect of age and treatment on predictive value of measurable residual disease: implications for clinical management of adult patients with acute myeloid leukemia.
Measurable residual disease (MRD) is a powerful predictor of outcome in acute myeloid leukemia (AML). In the early phases of treatment, MRD refines initial disease risk stratification and is used for the allocation to allogeneic transplant (HSCT). Despite its well-established role, a relatively high fraction of patients eventually relapses albeit achieving MRDneg status. The aim of this work was to assess specifically the influence of baseline features and treatment intensity on the predictive value of an MRDneg status, particularly focusing on MRD2, measured after 2 consecutive chemotherapeutic cycles. Among baseline features, younger MRD2neg patients (.