Clinical value of DSM IV and DSM 5 criteria for diagnosing the most prevalent somatoform disorders in patients with medically unexplained physical symptoms (MUPS).
This study aimed (1) to describe frequencies of DSM IV somatisation disorder, undifferentiated somatoform disorder and pain disorder versus DSM 5 somatic symptom disorder (SSD) in a multi-setting population of patients with medically unexplained physical symptoms (MUPS), (2) to investigate differences in sociodemographic and (psycho)pathological characteristics between these diagnostic groups and (3) to explore the clinical relevance of the distinction between mild and moderate DSM 5 SSD. We used baseline data of a cohort of 325 MUPS patients. Measurements included questionnaires about symptom severity, physical functioning, anxiety, depression, health anxiety and illness perceptions. These questionnaires were used as proxy measures for operationalization of DSM IV and DSM 5 diagnostic criteria. 92.9% of participants fulfilled criteria of a DSM IV somatoform disorder, while 45.5% fulfilled criteria of DSM 5 SSD. Participants fulfilling criteria of DSM 5 SSD suffered from more severe symptoms than those only fulfilling criteria of a DSM IV somatoform disorder(mean PHQ-15 score of 13.98 (SD 5.17) versus 11.23 (SD 4.71), P-value<0.001). Furthermore their level of physical functioning was significantly lower. Compared to patients with mild SSD, patients with moderate SSD suffered from significantly lower physical functioning and higher levels of depression. Within a population of MUPS patients DSM 5 SSD criteria are more restrictive than DSM IV criteria for somatoform disorders. They are associated with higher symptom severity and lower physical functioning. However, further specification of the positive psychological criteria of DSM 5 SSD may improve utility in research and practice.


Epidemiology and burden of HPV infection and related diseases: implications for prevention strategies.
Human papillomavirus (HPV) infection is a necessary, although not sufficient cause of cervical cancer. Globally, HPV infection accounts for an estimated 530,000 cervical cancer cases (~270,000 deaths) annually, with the majority (86% of cases, 88% of deaths) occurring in developing countries. Approximately 90% of anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. In total, HPV accounts for 5.2% of the worldwide cancer burden. HPVs 16 and 18 are responsible for 70% of cervical cancer cases and, especially HPV 16, for a large proportion of other cancers. Prophylactic vaccination targeting these genotypes is therefore expected to have a major impact on the burden of cervical cancer as well as that of other HPV-related cancers. Over the past 50 years, organized or opportunistic screening with Papanicolaou (Pap) cytology has led to major reductions in cervical cancer in most developed countries. However, due to lack of resources or inadequate infrastructure, many countries have failed to reduce cervical cancer mortality through screening. HPV DNA testing recently emerged as a likely candidate to replace Pap cytology for primary screening. It is less prone to human error and more sensitive than Pap in detecting high-grade cervical lesions. For countries with national vaccination programs, HPV testing may also serve as a low cost strategy to monitor long term vaccine efficacy. Introduction of well organized vaccination and screening programs should be a priority for all countries. Increased support from donors is needed to support this cause.


Further evidence that hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T and A1289C polymorphisms are not risk factors for schizophrenia.
It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups (P<0.01), which was mainly driven by the male group. The A1298C variant did not show any association with tHcy concentrations. In conclusion, these results do not confirm an independent relationship of tHcy and MTHFR genotype with risk of schizophrenia.


A method for measuring the experimental resolution of laboratory assays (clinical biochemical, blood count, immunological, and qPCR) to evaluate analytical performance.
The measurement method for experimental resolution and related data to evaluate analytical performance is poorly explored in clinical research. We established a method to measure the experimental resolution of clinical tests, including biochemical tests, automatic hematology analyzer methods, immunoassays, chemical experiments, and qPCR, to evaluate their analytical performance. Serially diluted samples in equal proportions were measured, and correlation analysis was performed between the relative concentration and the measured value. Results were accepted for p ≤ 0.01 of the correlation coefficient. The minimum concentration gradient (eg, 10%) was defined as the experimental resolution. For this method, the smaller the value, the higher the experimental resolution and the better the analytical performance. The experimental resolution of the most common biochemical indices reached 10%, with some even reaching 1%. The results of most counting experiments showed experimental resolution up to 10%, whereas the experimental resolution of the classical chemical assays reached 1%. Unexpectedly, the experimental resolution of more sensitive assays, such as immunoassays was only 25% when using the manual method and 10% for qPCR. This study established a method for measuring the experimental resolution of laboratory assays and provides a new index for evaluating the reliability of methods in clinical laboratories.


Brain abscess caused by Nocardia cyriacigeorgica in a patient with human immunodeficiency virus infection.
Nocardia cyriacigeorgica is a recently characterized species within the genus of Nocardia. We report a brain abscess, following a primary pulmonary colonization, due to this species in a human immunodeficiency virus-infected patient. This case confirms that isolation of Nocardia in sputum is associated with a high risk of disseminated infection in immunocompromised patients.


In vitro release of 5-fluorouracil with cyclic core dendritic polymer.
This paper describes the first synthesis of a series of dendritic polymers with a core of 1,4,7,10-tetraazacyclododecane. This core was allowed to react with methyl acrylate through a Michael addition and was then amidated with ethylenediamine. Repeating the two steps led to controlled molecular weight increasing and branching on the molecular level and produced four direction poly(amide-amine) dendrimers. We successfully synthesized dendrimers from generation 0. 5 to generation 5.5. Each generation was analyzed by Fourier- transform infrared (FT-IR) spectroscopy, 1H NMR and elemental analysis. Titrimetry was also used to determine the number of -NH2 of each full generation (2.0, 3.0, 4.0, 5.0). SEC (size exclusion chromatography) was performed to test the purity of G-3.0, G-4.0 and G-5.0. Parts of the outer layer -NH2 groups of the dendrimers generation 4 and generation 5 were acylated by acetic anhydride. The solubility in water of the dendrimer was thus greatly enhanced. The acetylated dendrimers were then reacted with 1-bromoacetyl-5-fluorouracil to form dendrimer-5FU conjugates. Hydrolysis of the conjugates in a phosphate buffer solution (pH 7.4) at 37 degreesC will release free 5FU. Different generation of dendrimer-5FU conjugates exert marking influence on the amount of 5FU released. The dendritic polymer seems to be a promising carrier for the controlled release of antitumor drugs.


Large-lateral-area SnO2 nanosheets with a loose structure for high-performance acetone sensor at the ppt level.
Gas sensors with high sensitivity and high selectivity are required in practical applications to distinguish between target molecules in the detection of volatile organic compounds, real-time security alerts, and clinical diagnostics. Semiconducting tin oxide (SnO2) is highly regarded as a gas-sensing material due to its exceptional responsiveness to changes in gaseous environments and outstanding chemical stability. Herein, we successfully synthesized a large-lateral-area SnO2 nanosheet with a loose structure as a gas sensing material by a one-step facile aqueous solution process without a surfactant or template. The SnO2 sensor exhibited a remarkable sensitivity (Ra/Rg = 1.33) at 40 ppt for acetone, with a theoretical limit of detection of 1.37 ppt, which is the lowest among metal oxide semiconductor-based gas sensors. The anti-interference ability of acetone was higher than those of pristine SnO2 and commercial sensors. These sensors also demonstrated perfect reproducibility and long-term stability of 100 days. The ultrasensitive response of the SnO2 nanosheets toward acetone was attributed to the specific loose large lateral area structure, small grain size, and metastable (101) crystal facets. Considering these advantages, SnO2 nanosheets with larger lateral area sensors have great potential for the detection and monitoring of acetone.


Biological wastewater treatment: Comparison of heterotrophs (BFT) with autotrophs (ABFT) in aquaculture systems.
The present study was conducted to compare wastewater purification capacities between heterotrophs (BFT) and autotrophs (ABFT) and to evaluate the effects on the growth of fish (Nile tilapia, Oreochromis niloticus) in aquaculture systems. The wastewater treatment capacity of heterotrophs is far superior to that of autotrophs, but the BFT system requires more energy for aquaculture than does the ABFT system. Regardless, both systems effected positive influences on fish growth performance, showing excellent water-purification capacities compared with the control group (CON). No significant differences were found between CON and ABFT or between ABFT and BFT, but there were significant differences between CON and BFT. Both systems BFT and ABFT were revealed to be cost effective in relation to CON, having reduced water replacement by 82%. Therefore, the BFT and ABFT systems could be economical aquaculture systems if due advantage is taken of what both have to offer.


Development of a reporter gene assay for antibody dependent cellular cytotoxicity activity determination of anti-rabies virus glycoprotein antibodies.
Rabies is a viral disease that is nearly 100% fatal once clinical signs and symptoms develop. Post-exposure prophylaxis can efficiently prevent rabies, and antibody (Ab) induction by vaccination or passive immunization of human rabies immunoglobulin (HRIG) or monoclonal antibodies (mAbs) play an integral role in prevention against rabies. In addition to their capacity to neutralize viruses, antibodies exert their antiviral effects by antibody-dependent cellular cytotoxicity (ADCC), which plays an important role in antiviral immunity and clearance of viral infections. For antibodies against rabies virus (RABV), evaluation of ADCC activity was neglected. Here, we developed a robust cell-based reporter gene assay (RGA) for the determination of the ADCC activity of anti-RABV antibodies using CVS-N2c-293 cells, which stably express the glycoprotein (G) of RABV strain CVS-N2c as target cells, and Jurkat cells, which stably express FcγRⅢa and nuclear factor of activated T cells (NFAT) reporter gene as effector cells (Jurkat/NFAT-luc/FcγRⅢa cells). The experimental parameters were carefully optimized, and the established ADCC assay was systematically validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 guideline. We also evaluated the ADCC activity of anti-RABV antibodies, including mAbs, HRIG, and vaccine induced antisera, and found that all test antibodies exhibited ADCC activity with varied strengths. The established RGA provides a novel method for evaluating the ADCC of anti-RABV antibodies.


The use of amniotic fluid AFP action limits in diagnosing open neural tube defects.
An analysis is made of alphafetoprotein (AFP) concentrations in 3630 amniotic fluids submitted for prospective prenatal diagnoses over a 7-year period. There were 89 cases of anencephaly, 74 of open spina bifida and 3467 with normal singleton outcomes. The AFP data were expressed in both standard deviations above the mean and multiples of the normal median for individual weeks of gestation. False positive and false negative rates were comparable in the two systems at selected cut-offs. It is concluded that either system may be used in setting action limits for the primary distinction of unaffected pregnancies from those in which an open neural tube defect is present.


Structural and biochemical elements of efficiently degradable proteasome substrates.
Most regulated proteolysis in cells is conducted by the ubiquitin-proteasome system (UPS), in which proteins to be eliminated are selected through multiple steps to achieve high specificity. The large protease complex proteasome binds to ubiquitin molecules that are attached to the substrate and further interacts with a disordered region in the target to initiate unfolding for degradation. Recent studies have expanded our view of the complexity of ubiquitination as well as the details of substrate engagement by the proteasome and at the same time have suggested the characteristics of substrates that are susceptible to proteasomal degradation. Here, I review some destabilizing elements of proteasome substrates with particular attention to ubiquitination, initiation region and stability against unfolding and discuss their interplay to determine the substrate stability. A spatial perspective is important to understand the mechanism of action of proteasomal degradation, which may be critical for drug development targeting the UPS including targeted protein degradation.


Changes in morphology and infectivity of cell culture-derived trypomastigotes of Trypanosoma cruzi.
Trypomastigotes of Trypanosoma cruzi, obtained from the first burst of infected Vero cells, have only a limited invasive capability for fibroblastic cells. Intracellular amastigotes and epimastigotes do not infect these cells at all. Preincubation of the isolated trypomastigotes with Eagle's minimal essential medium/10% fetal calf serum increases 5- to 15-fold their in vitro infectivity. This increased invasive capability is accompanied, in the case of the EP strain of T. cruzi, by a morphological transformation into an amastigote-like or spheromastigote form, which is similar, but not identical to replicating intracellular amastigotes. Trypomastigotes from another isolate (BEC) also increase their infectivity several fold upon preincubation, but before any morphological differentiation occurs, suggesting that these two events are independent. The phenomenon of increased infective capability of the parasite is expressed similarly in different host cells. Parasite adhesion is stimulated 4- to 12-fold upon preincubation of the trypomastigotes. The type of serum used (fetal calf, calf, human) affects the development of infectivity, as well as the process of cell infection in itself, but not the morphological differentiation. These processes are also temperature-dependent. The highly infective parasitic forms do not synthetize DNA, but are active in RNA and protein synthesis. The results obtained indicate the existence in T. cruzi trypomastigotes of an active system for infecting fibroblastic cells, which is only partially expressed in trypomastigotes recently released from host fibroblasts but which can undergo a further extracellular maturation, thus allowing studies on the mechanism of infection in cell-free media.


Replacing the combitube by an endotracheal tube using a fibre-optic bronchoscope during spontaneous ventilation.
We present a case of microlaryngoscopy in a patient with an unexpectedly difficult airway. The airway was managed by using an oesophageal-tracheal Combitube (Kendall-Sheridan, Argyle, NY) (ETC) and a fibre-optic bronchoscope (Pentax-Japan-5 mm).


Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials.
Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years. We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment. Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed. Of the 944 individuals receiving ≥1 PTAH dose, median exposure was ∼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis]). The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH.


Internal fixation of mandibular angle fractures: a comparison of 2 techniques.
To compare treatment outcomes between rigid extraoral fixation and semirigid intraoral fixation for the management of isolated mandibular angle fractures, and to develop a protocol for successfully managing these fractures in an indigent population. This study involved a retrospective analysis of mandibular angle fracture patients treated at Boston Medical Center from 1999 to 2006. All patients were treated by a single attending surgeon, with oral and maxillofacial surgery residents. Data were collected by a review of pertinent inpatient and outpatient clinic records, and radiographic and laboratory results. The criteria for inclusion into the study comprised: 1) patients with isolated unilateral or bilateral mandibular angle fractures; 2) surgical treatment provided within 7 days of injury via 1 of the 2 following techniques: a) open reduction and internal fixation via an intraoral approach (single monocortical miniplate), or b) open reduction and internal fixation (ORIF) via an extraoral approach (inferior border plate with at least 2 holes on either side of the fracture line and bicortical screws); 3) the presence of decayed, partially bony, or full bony impacted third molars requiring removal at time of surgery; 4) the use of postsurgical maxillomandibular fixation (MMF) for 1 week (extraoral rigid-fixation cases) and 2 weeks (intraoral semirigid-fixation cases) and 5) a 1-week duration of postsurgical oral antibiotic therapy. The patient sample ranged in age from 17 to 55 years, with an average age of 24.8 years. The average follow-up was 12.3 weeks (range, 8 to 64 weeks). In total, 98 fractures were treated with intraoral miniplate fixation, whereas 65 fractures underwent rigid fixation using an extraoral approach. The presence or absence of bone gaps in radiographs immediately after surgery had no correlation with surgical success. None of the patients in either group required further surgical intervention in the operating room. Patients with postsurgical infections were successfully managed with localized intraoral incision and drainage, and oral antibiotic therapy. Isolated mandibular angle fractures can be effectively treated in an indigent population with either intraoral monocortical fixation or extraoral bicortical fixation techniques. Use of a standard protocol involving early surgical management with limited periosteal reflection, concomitant removal of third molars, and short-term maxillomandibular fixation ensures predictable success with a low incidence of complications.


Support of hypoxic renal cell volume regulation by glycine.
PO2 declines to less than 10 mm Hg in local regions of the renal cortex. Amino acids seem to modify the hypoxic tolerance of renal cells. It was suggested that glycine may support renal function in hypoxia. Aim of the present study was to test the effect of glycine on renal cellular hypoxic tolerance. We isolated tubules of the rat kidney cortex (ITS) by collagenase treatment and measured cellular function at different levels of extracellular oxygen tensions (1, 2.5, 5, 10, 40, and 100 mm Hg) both with and without glycine in the incubation medium. No significant effects were observed in the "physiological" range at an extracellular PO2 = 100-10 mm Hg. With no glycine in the incubation medium, the outer tubular diameter of ITS rose at lower oxygen tensions, at PO2 of 1 mm Hg by about 170%, and the loss of 4 marker enzymes increased about 2-4 fold. Hypoxic lactate formation increased at extracellular oxygen tensions less than 10 mm Hg. Intracellular K+ fell in parallel to about one third of the aerobic control values. Addition of glycine to the incubation medium did not significantly change intracellular K+ or anaerobic lactate formation. In contrast, the loss of marker enzymes was significantly suppressed by glycine, lysosomal APase and mitochondrial GlDH by about 30%, cytoplasmatic LDH and brush border tau GT by about 50%. Accordingly, at PO2 = 1 mm Hg the hypoxic swelling of renal cells was suppressed in the presence of glycine by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)


Emergence of two Escherichia coli strains co-harboring mcr-1 and bla NDM in fresh vegetables from China.
The concurrence of mcr and carbapenemase genes among Enterobacteriaceae has been a great clinical concern. In our study, we aimed to investigate the prevalence of mcr-positive carbapenem-resistant Enterobacteriaceae (CRE) in fresh vegetables and shed light on the possibility of transmission of mcr-positive CRE via fresh vegetables. In this study, 712 fresh vegetable samples from 10 provinces in China were collected between May 2017 and Dec 2018 and were screened for mcr and carbapenemase genes. Antibiotic susceptibilities for isolates co-harboring carbapenemase genes and mcr were determined by an agar dilution or a broth microdilution method. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis were also performed. Transferability of the carbapenemase/mcr-bearing plasmids was determined by conjugation, replicon typing and S1-PFGE-Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Hiseq platform. Two E. coli isolates concomitantly carrying mcr-1 and bla NDM-5/9 from leaf rape and spinach, respectively, were found and both isolates showed multidrug resistance. Notably, mcr-1-positive 690 harboring bla NDM-5 and 701 carrying bla NDM-9 belonged to ST156 and ST2847, respectively, similar to the prevalent MLST types of E. coli co-carrying mcr-1 and bla NDM from avian in our previous study. mcr-1 was on ~33-kb IncX4 plasmid or ~60-kb IncI2 plasmid, while bla NDM-5/9 was on ~46-kb IncX3 plasmid or ~120-kb untypable plasmid. The plasmids were highly similar to those from animals and clinical patients reported in various countries.Conclusion: E. coli isolates concomitantly carrying mcr-1 and bla NDM-5/9 in fresh vegetables may serve as a direct source of pathogens in humans, and such discovery in fresh vegetables emphasizes the importance of prompt surveillance and intervention in limiting the spread of E. coli co-carrying bla NDM and mcr-1. To our knowledge, this is the first report of Enterobacteriaceae co-carrying bla NDM and mcr-1 in fresh vegetables.


Efficiency transfer using the GEANT4 code of CERN for HPGe gamma spectrometry.
In this work we apply the GEANT4 code of CERN to calculate the peak efficiency in High Pure Germanium (HPGe) gamma spectrometry using three different procedures. The first is a direct calculation. The second corresponds to the usual case of efficiency transfer between two different configurations at constant emission energy assuming a reference point detection configuration and the third, a new procedure, consists on the transfer of the peak efficiency between two detection configurations emitting the gamma ray in different energies assuming a "virtual" reference point detection configuration. No pre-optimization of the detector geometrical characteristics was performed before the transfer to test the ability of the efficiency transfer to reduce the effect of the ignorance on their real magnitude on the quality of the transferred efficiency. The obtained and measured efficiencies were found in good agreement for the two investigated methods of efficiency transfer. The obtained agreement proves that Monte Carlo method and especially the GEANT4 code constitute an efficient tool to obtain accurate detection efficiency values. The second investigated efficiency transfer procedure is useful to calibrate the HPGe gamma detector for any emission energy value for a voluminous source using one point source detection efficiency emitting in a different energy as a reference efficiency. The calculations preformed in this work were applied to the measurement exercise of the EUROMET428 project. A measurement exercise where an evaluation of the full energy peak efficiencies in the energy range 60-2000 keV for a typical coaxial p-type HpGe detector and several types of source configuration: point sources located at various distances from the detector and a cylindrical box containing three matrices was performed.


Size-selective assessment of agricultural workers' personal exposure to airborne fungi and fungal fragments.
Fungi are ubiquitous agents that cause human respiratory diseases. Very few studies have size-selectively assessed farmers' exposure to fungi and fungal fragments in agricultural settings. In this study, a two-stage bio-aerosol cyclone personal sampler was employed to collect airborne fungi and fungal fragments size-selectively at corn, swine, poultry, and mushroom farms. The collected air samples were analyzed for culturable fungi, fungal spores, viable fungi and (1 → 3)-β-D-glucan. The results show that the median concentrations ranged from 3.2 × 10(5) to 1.3 × 10(8)spores/m(3) for total fungal spores, from 1.3 × 10(5) to 5.1 × 10(7)spores/m(3) for total viable fungi, from 1.9 × 10(3) to 1.5 × 10(7)CFU/m(3) for total culturable fungi, and from 4.3 × 10(3) to 2.4 × 10(6)pg/m(3) for total (1 → 3)-β-D-glucan. The aerodynamic sizes of most of the collected fungal contaminants were larger than 1.8 μm. Total (1 → 3)-β-D-glucan significantly correlated with total fungal spores (r = 0.65, p < 0.001), total viable fungi (r = 0.68, p < 0.001) and total culturable fungi (r = 0.72, p < 0.001). Total (1 → 3)-β-D-glucan significantly correlated with Aspergillus/Penicillium, Alternaria, and Cladosporium. Alternaria and Botrytis were also found to highly correlate with (1 → 3)-β-D-glucan at the size <1 μm, which was less than the expected spore sizes (the mean measured aerodynamic sizes were 18.5 μm for Alternaria and 6.1 μm for Botrytis); therefore, Alternaria and Botrytis might release small fragments that could enter the deep lung and cause respiratory diseases.


Para-chloro-meta-xylenol reshaped the fates of antibiotic resistance genes during sludge fermentation: Insights of cell membrane permeability, bacterial structure and biological pathways.
The occurrence of para-chloro-meta-xylenol (PCMX, as largely consumed antimicrobial chemicals) in waste activated sludge (WAS) would pose environmental risks for WAS utilization. This study revealed that PCMX principally prompted the abundances and diversity of antibiotic resistance genes (ARGs), particularly for the multidrug- genes (i.e., acrB and mexW), and reshaped the resistance mechanism categories during WAS fermentation process. The genotype and phenotype results indicated that PCMX upregulated abundances of transposase and increased cell permeability via disrupting WAS structure, which further facilitated the horizontal transfer of ARGs. The network and correlation analysis among ARGs, mobile genetic elements (MGEs) and genera (i.e., Sphingopyxis and Pseudoxanthomonas) verified that PCMX enriched the potential ARGs hosts associated with multidrug resistance mechanism. Also, PCMX upregulated the genes involved in ARGs-associated metabolic pathways, such as two-component (i.e., phoP and vcaM) and quorum sensing systems (i.e., lasR and cciR), which determined the ARGs proliferation via multidrug efflux pump and outer membrane proteins, and facilitated the recognition between ARGs hosts. Variance partitioning analysis (VPA) implied that the shift of microbial community contributed predominantly to the dissemination of ARGs. These findings unveiled the environmental behaviors and risks of exogenous pollutants in WAS with insightful understanding, which could guide the WAS utilization for resource recovery.


The rebirth of kinship: evolutionary and quantitative approaches in the revitalization of a dying field.
Kinship was one of the key areas of research interest among anthropologists in the nineteenth century, one of the most hotly debated areas of theory in the early and mid-twentieth century, and yet an area of waning interest by the end of the twentieth century. Since then, the study of kinship has experienced a revitalization, with concomitant disputes over how best to proceed. This special issue brings together recent studies of kinship by scientific anthropologists employing evolutionary theory and quantitative methods. We argue that the melding of the evolutionary theoretical perspective with quantitative and ethnographic methodologies has strengthened and reinvigorated the study of kinship by synthesizing and extending existing research via rigorous analyses of evidence.


Terms of madness: historical linguistics.
The etymological origins of commonly used descriptors of mental conditions are explored. In reviewing history for signs of mental disorders, we need to understand the terms used previously to indicate abnormalities. A wealth of terms is evident indicating that, contrary to the conclusions of some historians, mental illnesses have an extended and broad history.


Hypocalcemia during restraint stress in rats. Indication that gastric ulcer prophylaxis by exogenous calcium interferes with calcitonin release.
The influence of restraint stress on serum calcium (Ca) and phosphate was studied in normal and thyroidectomized rats. In addition the response of gastric stress ulcer index, blood gastrin and glucagon to exogenous Ca was investigated. In intact as well as in thyroidectomized animals serum total, ionised and previously injected radioactive Ca decrease during an 8h stress period, whereas inorganic phosphate increases. Together with a constant specific activity these findings are consistent with hypoparathyroidism and calcitonin independent hypocalcemia during stress. Intragastric infusion of 45 mg/kg Ca-gluconate per 8h proves to be a potent anti-stress ulcer regimen in intact and neck-sham operated, but not in thyroidectomized rats without and with additional adrenal demedullation. Gastrin and glucagon were not correlated with calcemia during either stress alone or stress combined with intragastric Ca infusion. It is suggested that the development of gastric stress ulcerations can be prevented by a Ca-mediated release of endogenous calcitonin.


C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids: a conformation-activity study.
Among a series of C-alkylated analogs of the weak mu opioid ligand spiro[benzofuran-3(2H),4'-1'-methylpiperidine-7-ol] (1), the 2-methyl, 2-ethyl, and cis 3'-methyl analogs, namely compounds (+/-)2, (+/-)-3, and (+/-)-4, showed much enhanced mu-affinities, with (+/-)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (+/-)-5 remained a weak mu-binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.


'Unicorn' among rats exposed to mycotoxins from Fusarium.
A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.


Target areas innervated by PACAP-immunoreactive retinal ganglion cells.
The retinohypothalamic tract (RHT) originates from a subset of retinal ganglion cells (RGCs). The cells of the RHT co-store the neurotransmitters PACAP and glutamate, which in a complex interplay mediate light information to the circadian clock located in the suprachiasmatic nuclei (SCN). These ganglion cells are intrinsically photosensitive probably due to expression of melanopsin, a putative photoreceptor involved in light entrainment. In the present study we examined PACAP-containing retinal projections to the brain using intravitreal injection of the anterograde tracer cholera toxin subunit B (ChB) and double immunostaining for PACAP and ChB. Our results show that the PACAP-containing nerve fibres not only constituted the major projections to the SCN and the intergeniculate leaflet of the thalamus but also had a large terminal field in the olivary pretectal nucleus. The contralateral projection dominated except for the SCN, which showed bilateral innervation. PACAP-containing retinal fibres were also found in the ventrolateral preoptic nucleus, the anterior and lateral hypothalamic area, the subparaventricular zone, the ventral part of the lateral geniculate nucleus and the nucleus of the optic tract. Retinal projections not previously described in the rat also contained PACAP. These new projections were found in the lateral posterior nucleus, the posterior limitans nucleus, the dorsal part of the anterior pretectal nucleus and the posterior and medial pretectal nuclei. Only a few PACAP-containing retinal fibres were found in the superior colliculus. Areas innervated by PACAP-immunoreactive fibres also expressed the PACAP-specific PAC1 receptor as shown by in situ hybridization histochemistry. The findings suggest that PACAP plays a role as neurotransmitter in non-imaging photoperception to target areas in the brain regulating circadian timing, masking, regulation of sleep-wake cycle and pupillary reflex.


miR-130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF-β-PI3K/AKT signaling pathway.
Sertoli cells play vital roles in normal spermatogenesis, and microRNAs (miRNAs) participate in regulating Sertoli cell development. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. Herein, we primarily explored the regulatory roles of miR-130a in immature porcine Sertoli cells using EdU-based high-content screening assay. The results demonstrated that 27 miRNAs have potential roles in the promotion of immature porcine Sertoli cell proliferation, and miR-130a was identified as a promising candidate. miR-130a promoted cell cycle progression and cell proliferation, whereas it impeded cell apoptosis in immature porcine Sertoli cells. It also contributed to Sertoli cell proliferation and testis development in vivo. A TMT-based proteomics approach revealed that miR-130a regulated the expression of 91 proteins and multiple pathways, including the TGF-β and PI3K/AKT signaling. miR-130a did not directly target the 3'-UTR of SMAD5; however, it increased SMAD5 phosphorylation. Moreover, miR-130a enhanced TGF-β signaling by activating SMAD5 protein, and TGF-β signaling further activated the PI3K/AKT signaling pathway to promote cell proliferation and inhibit cell apoptosis in porcine immature Sertoli cells. Collectively, miR-130a promoted immature porcine Sertoli cell growth by activating SMAD5 through the TGF-β-PI3K/AKT signaling pathway. This study, therefore, provides novel insights into the effects of miR-130a on porcine spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.


Assessment of the ventricular fibrillation detection algorithm in the semi-automatic Cardio-Aid defibrillator.
The sensitivity and specificity of ventricular fibrillation (VF) detection in the semi-automatic Cardio-Aid defibrillator was assessed with 25 ECG recordings, each of length 40 s. Of the 25 ECG recordings, 12 contained VF requiring defibrillation, 3 contained a tachyarrhythmia with a waveform similar to VF but which self-terminated, and 10 were selected from abnormal rhythms and artefacts which contained some features similar to VF. Sensitivity was assessed from the VF data. Specificity was assessed from both the rhythm preceding VF or the tachyarrhythmias, and from the VF-like data. The response to a changing rhythm was assessed from the self-terminating tachyarrhythmias. Each recording was replayed to the defibrillators at 3 signal amplitudes (normal, half and double). Request to analyse the ECG because of possible VF and advice to shock were noted separately. The sensitivity for recommending a shock when a shock was required was 92%. The sensitivity for drawing attention to VF, through requesting analysis was 97%. There were no false detections in the rhythms preceding VF or the tachyarrhythmias (specificity with good quality signals 100%). The specificity with the VF-like data ws 90%. There was significant difference between this defibrillator and other semi-automated defibrillators previously assessed.


AO/OTA 31A3 fractures and postoperative complications in older patients.
AO/OTA 31A3 fractures (A3 fractures) have risk for postoperative complications with major impact on morbidity and mortality. For older patients, limited information is available for factors associated with postoperative complications. We aimed to assess factors associated with postoperative complications after surgery using cephalomedullary nails. A retrospective cohort study was conducted using the information on patients aged ≥65 years who underwent surgery using cephalomedullary nails for trochanteric fractures due to low-energy trauma in three hospitals. Postoperative complications were diagnosed when patients were identified as nonunion, cutout of lag screw, or nail breakage. First, we compared differences including age, sex, body mass index, American Society of Anesthesiologists physical status classification system, preoperative waking ability, fracture type, nail length, neck shaft angle, reduction method, reduction quality and tip apex distance between patients with and without postoperative complications. Second, multivariable logistic regression analysis was employed to assess factors associated with postoperative complications resulting from A3 fractures. Among 120 patients with A3 fractures, postoperative complications were identified in 12 patients (10.0%). Postoperative complications were significantly more likely to develop among patients with poor reduction quality (adjusted odds ratio [95% confidence interval], 35.0 [4.43-275.9]) and a tip-apex distance ≥25 mm (16.4 [1.92-140.3]). These findings suggest that surgeons should aim to perform appropriate postoperative reduction and to prevent postoperative complications when using a cephalomedullary nail for A3 fractures among older patients.


Polyethylenimine improves the transfection efficiency of primary cultures of post-mitotic rat fetal hypothalamic neurons.
Analysis of gene regulatory sequences in primary cultures of neurons has been hampered by inefficient transfection of post-mitotic neurons with reporter plasmids. We describe detailed conditions that allowed a significant improvement of transfection efficiency in primary cultures of serum-supplemented rat fetal hypothalamic cells. Transfected cells expressed the green fluorescent protein (GFP) under the control of the strong but non-cell-specific cytomegalo virus (CMV) promoter or under the thyrotropin-releasing hormone (TRH) promoter, to direct expression only in TRH neurons. Using the CMV promoter-GFP plasmid, we tested several commercially available transfection reagents; the best results were obtained with polyethylenimine (PEI) and Lipofectamine 2000. We optimized the transfection procedure with PEI because it rendered more reproducible results. Transfection with PEI was optimal when cells were transfected at a cellular density of 2.9 x 10(6) cells in 35-mm dishes, with 10 microg of DNA, a PEI/DNA ratio of 8.8 and PEI pH of 6.9. Using these conditions, we were able to detect GFP positive neurons after transfecting the TRH promoter-GFP plasmid. GFP positive cells were successfully purified by FACS. This opens the possibility to use transfection of mammalian CNS post-mitotic neurons for new applications including the purification of specific neuronal subtypes.


Epidermoids and dermoids of the calvarian bones in early childhood: their behaviour in the growing skull.
Thirteen out of 25 cystic lesions of the infantile skull, radiographically classified as epidermoids or dermoids of the calvarian bones, disappeared spontaneously during early childhood. A further six lesions showed involution. In all, 19/25 lesions were involutive. In no case did we find an enlargement which could be attributed with certainly, to growth after the age of 3 years. These findings strongly support the opinion of Fauré that by far most of these lesions are non-evolutive and generally do not need surgical treatment. Only lesions which do persist beyond the third year of life and grow continuously or begin to grow again need to be operated. Thus, we recommend a conservative attitude and a radiographic follow-up at long intervals.


[Expression and its clinical significance of SLC22A18 in non-small cell lung cancer].
It has been proven that multidrug resistance (MDR) is the main cause of chemotherapy failure in lung cancer. Research on emergence mechanisms of MDR has great clinical significance in improving the curative efficiency of lung cancer chemotherapy. Proteins encoded by the SLC22A18 gene, which is similar to the transmembrane transporter, may influence the sensitivity of chemotherapeutics as well as the metabolism and growth of cells. In addition, these proteins probably have some effect on the development of lung cancer MDR. The aim of the present study is to investigate the expression of SLC22A18 protein in non-small cell lung cancer (NSCLC) as well as in corresponding normal lung tissue. Furthermore, the relationship between SLC22A18 expression and pathological grade and TNM stage is analyzed. The expression of SLC22A18 was detected by EnVinsion in 96 cases with NSCLC and in corresponding normal lung tissue. Statistical analysis was performed using SPSS 17.0 statistical software. SLC22A18 was mainly located in cell membrane and cytoplasm. The expression level of SLC22A18 in NSCLC was significantly higher than that in normal tissue (P<0.01). The positive rates in squamous cell lung cancer and lung adenocarcinoma were 68% and 78.2%, respectively (P<0.05). Moreover, the higher expression of SLC22A18 was associated with lower histological grade and later TNM stage (P<0.05). SLC22A18 protein is overexpressed in NSCLC, and its expression is correlated with pathological grade and TNM stage. These findings provide the experimental basis for investigating the role of tumor and chemoresistance.


[Lesions detected in a colorectal cancer screening program in the Basque Country: first round (2009-2011)].
Colorectal cancer (CRC) is a major public health problem due to its incidence and mortality. In May 2008, the Basque Country approved the implementation of a population-based colorectal cancer screening program, using the immunochemical fecal occult blood test (FOBT), in persons aged 50-69 years. Patients with a positive result were invited to undergo colonoscopy with sedation. To describe the main results of the first round of the CRC screening program with FOBT (2009-2011) in terms of the detection rates and positive predictive value (PPV). Retrospective study of participation rates and colonoscopic findings in persons with a positive FOBT result. Invitations to attend screening were sent to 230.505 persons. A total of 148.249 FOBT tests were processed. The mean participation rate was 64.3% (95% CI: 64.1-64.5) and was higher in women than in men. The FOBT test was positive in 6.7% (95% CI: 6.6-6.8). Positive results were more frequent in men. Among persons with a positive result, colonoscopy was performed in 93.1%. There were significant differences between women and men in the detection rate of high-risk adenomas (OR: 0,45 95% CI 0,41-0,49), which, as with CRC (OR: 0,80 95% CI 0,66-0,96), were more frequent in men. The PPV for adenoma of any type was significantly higher in men (72.4 95% CI, 71.2-73.5) than in women (48.8% 95% CI 47.2-50.5), with differences by age group and type of adenoma. Participation rates and detection of advanced lesions and CRC were high. Because men have a higher risk of developing CRC, efforts should be made to increase their participation. The impact of the CRC screening program should be evaluated in the medium to long term.


Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure.
The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 ± 0.03%), and tended to increase the p-AKTser473 /AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. ClinicalTrials.gov (Identifier: NCT01747395).


Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota.
As a conserved pathway that lies at the intersection between host defence and cellular homeostasis, autophagy serves as a rheostat for immune reactions. In particular, autophagy suppresses excess type I interferon (IFN-I) production in response to viral nucleic acids. It is unknown how this function of autophagy relates to the intestinal barrier where host-microbe interactions are pervasive and perpetual. Here, we demonstrate that mice deficient in autophagy proteins are protected from the intestinal bacterial pathogen Citrobacter rodentium in a manner dependent on IFN-I signalling and nucleic acid sensing pathways. Enhanced IFN-stimulated gene expression in intestinal tissue of autophagy-deficient mice in the absence of infection was mediated by the gut microbiota. Additionally, monocytes infiltrating into the autophagy-deficient intestinal microenvironment displayed an enhanced inflammatory profile and were necessary for protection against C. rodentium. Finally, we demonstrate that the microbiota-dependent IFN-I production that occurs in the autophagy-deficient host also protects against chemical injury of the intestine. Thus, autophagy proteins prevent a spontaneous IFN-I response to microbiota that is beneficial in the presence of infectious and non-infectious intestinal hazards. These results identify a role for autophagy proteins in controlling the magnitude of IFN-I signalling at the intestinal barrier.


Meningeal melanocytoma in the left frontal region.
We report a rare case of meningeal melanocytoma in the left frontal region. A 45-year-old man complained of a headache. Magnetic resonance (MR) scanning showed characteristic patterns: a slightly high signal intensity mass in the left frontal region on the T1-weighted image and a low signal intensity on the T2-weighted image. The patient underwent gross total removal of the tumor. The postoperative course was uneventful. After two years, there was a small local recurrence. The histological finding of the tumor showed meningeal melanocytoma. To our knowledge, this is the second published report of a meningeal melanocytoma in the supratentorial region.


The cytoplasmic loops of subunit a of Escherichia coli ATP synthase may participate in the proton translocating mechanism.
Subunit a plays a key role in promoting H(+) transport and the coupled rotary motion of the subunit c ring in F(1)F(0)-ATP synthase. H(+) binding and release occur at Asp-61 in the middle of the second transmembrane helix (TMH) of F(0) subunit c. H(+) are thought to reach Asp-61 via aqueous pathways mapping to the surfaces of TMHs 2-5 of subunit a based upon the chemical reactivity of Cys substituted into these helices. Here we substituted Cys into loops connecting TMHs 1 and 2 (loop 1-2) and TMHs 3 and 4 (loop 3-4). A large segment of loop 3-4 extending from loop residue 192 loop to residue 203 in TMH4 at the lipid bilayer surface proved to be very sensitive to inhibition by Ag(+). Cys-161 and -165 at the other end of the loop bordering TMH3 were also sensitive to inhibition by Ag(+). Further Cys substitutions in residues 86 and 93 in the middle of the 1-2 loop proved to be Ag(+)-sensitive. We next asked whether the regions of Ag(+)-sensitive residues clustered together near the surface of the membrane by combining Cys substitutions from two domains and testing for cross-linking. Cys-161 and -165 in loop 3-4 were found to cross-link with Cys-202, -203, or -205, which extend into TMH4 from the cytoplasm. Further Cys at residues 86 and 93 in loop 1-2 were found to cross-link with Cys-195 in loop 3-4. We conclude that the Ag(+)-sensitive regions of loops 1-2 and 3-4 may pack in a single domain that packs at the ends of TMHs 3 and 4. We suggest that the Ag(+)-sensitive domain may be involved in gating H(+) release at the cytoplasmic side of the aqueous access channel extending through F(0).


In-Situ Simulation for Intensive Care Nurses During the COVID-19 Pandemic in Italy: Advantages and Challenges.
The COVID-19 pandemic required a global increase in intensive care unit (ICU) resources and the recruitment of a great number of nurses without any tprior critical care experience. The opportunities for traditional education and supervised clinical training were limited to prevent infections. The massive increase of nursing staff resources required a rethinking of the usual educational strategies for newly acquired nurses. This short communication describes our experience of an "in-situ" simulation training course in an Italian tertiary level hospital. A series of two-part classes were structured with short lectures on fundamental principles of intensive care nursing and brief hands-on sessions, and a set of simulated scenarios, based upon the most common situations to be faced in the ICU. In-situ simulation offers greater realism and transferability and represents a cost-effective strategy, avoiding the costs and the maintenance of a dedicated simulation center. The simulated multidisciplinary teamwork in the real ICU setting contributes to an effective experiential learning, improving staff familiarity with devices, equipment, and environment, and allows trainees to improve both technical and nontechnical skills.


Bilateral facial nerve palsy associated with Epstein-Barr virus infection with a review of the literature.
A case of bilateral simultaneous facial nerve palsy associated with an Epstein-Barr virus (EBV) infection in a 14-month-old girl is described. Diagnosis of the EBV infection was based on the presence of 7% atypical lymphocytes, EBV-DNA and seroconversion in the VCA-IgG antibody, an EBV-specific antibody. Although bilateral facial nerve palsy is very rare, approximately 40% of the EBV-associated facial nerve palsy cases reported have been bilateral.


Dendrobium officinale Kimura & Migo polysaccharide inhibits hyperglycaemia-induced kidney fibrosis via the miRNA-34a-5p/SIRT1 signalling pathway.
Fibrosis is a fundamental change occurring in impaired renal function and plays an important role in the progression of diabetic kidney disease (DKD). Dendrobium officinale Kimura & Migo polysaccharide (DOP), a primary active component of Dendrobium officinale Kimura & Migo, is reported to act on reducing blood glucose, suppressing inflammation. However, the anti-fibrosis effect of DOP in the treatment of DKD is still unclear. To explore the therapeutic effect of DOP on renal fibrosis in DKD. We used db/db mice as a DKD model and administered DOP by oral gavage. The expression of miRNA-34a-5p, SIRT1, and fibrosis molecules (TGF-β, CTGF, and a-SMA) were detected in renal tissue. Human renal tubular epithelium cells (HK-2) were cultured with 5.5 mM glucose (LG) or 25 mM glucose (HG), and intervened with 100-400 μg/ml DOP. The changes of the above indicators were observed in vitro. MiRNA-34a-5p was mainly localised in the nucleus and increased expression in the DKD mice. Inhibition or excitation of miRNA-34a-5p is involved in renal fibrosis by regulating SIRT1. DOP could depress the miRNA-34a-5p/SIRT1 signalling pathway to relieve renal fibrosis. Moreover, DOP has outstanding results in the treatment of DKD through hypoglycaemic action and weight reduction. DOP plays a protective role in arresting or slowing the progression of fibrosis, which may provide a novel clinical treatment strategy for DKD.


The effect of relaxin on calcium fluxes in the rat uterus.
Relaxin is a polypeptide hormone that inhibits rat uterine contractions. To test the hypothesis that the mechanism of action of this effect may involve shifts in calcium ions, the biologic action of relaxin on isolated rat uterine horns was directly correlated with measurements of 45Ca2+ efflux from and uptake into the tissues. Kinetic analysis demonstrated that the efflux of 45Ca2+ from rat uterine horns was significantly faster when tissue was incubated with 25 ng/ml relaxin as compared with control tissues incubated with no relaxin. In addition, at the end of the efflux experiments, control uteri contained 3.9% of the starting 45Ca2+, whereas the relaxin-treated uteri contained only 2.55%, indicating greater total Ca2+ efflux from the relaxin-treated horns (p less than 0.05). The effect of relaxin on 45Ca2+ uptake by uterine tissue was also studied. Analysis of uptake curves by linear regression demonstrated that relaxin treatment leads to less total uptake of 45Ca2+ in the uterine tissue, although the differences are not statistically significant. These experiments demonstrate that relaxin inhibition of rat uterine contractions in vitro is associated with a decrease in intracellular free Ca2+, caused, at least in part, by the promotion of Ca2+ efflux. These results represent the first step in defining the mechanism of action of this hormone.


Automated anesthesia surgery medical record system.
Manual recording of physiological data in patients receiving anesthesia or intensive care infrequently meets medical requirements or legal documentation standards. Automated recording allows the generation of reliable data that can be integrated into the patient's medical record. Such a system is beginning to function at University Hospital at Stony Brook, New York. Bedside medical devices (pulse oximeters, non-invasive blood pressure monitors, capnographs, infusion pumps and physiological monitors) from 18 operating rooms and 16 beds in the Anesthesia Intensive Care Unit are connected to a baseband Ethernet system. Data from the above devices are stored in a MicroVAX computer system. Data compression and interpretation, computation of derived values, statistical analysis of data from two related parameters are done by the bedside graphical microcomputer workstation. The MicroVAX computer and the workstation are also connected to the Ethernet system. The overall architecture of the automatic record system conforms to emerging standards for information exchange between bedside monitors and computer systems. Health care recipients and providers are likely to reap the benefits.


Survival, growth and persistence under farm conditions of a Lactobacillus plantarum strain inoculated into liquid pig feed.
To investigate the survival and persistence of Lactobacillus plantarum REB1 in the fermentation process of liquid pig feed on a working farm in standard production conditions. Two feed types, a control diet [nonfermented liquid feed (NFLF)] and a fermented diet [fermented liquid feed (FLF)], were compared. A rifampicin-resistant mutant L. plantarum REB1-Rif was used to initiate the fermentation of the feed. Inoculation with the experimental strain was repeated one or two times per week throughout the three month growing period. Four microbial groups were followed using standard microbiological techniques, as well as pH. Lactic acid bacteria (LAB) counts were high already at the beginning in FLF, while it took nine days to reach the corresponding LAB levels in NFLF. Yeasts were stable in FLF, whereas in NFLF there were occasional high counts during the first week. The numbers of Enterobacteriaceae were low, although in NFLF they were variable. The average pH in NFLF was 4.5 and 4 in FLF. The inoculation of L. plantarum REB1-Rif provided a LAB population of log 9 colony forming units (CFU) ml(-1) from the first feeding day, stable numbers of yeast and pH, and a drastic reduction of Enterobacteriaceae. The inoculation by L. plantarum REB1-Rif offered a FLF microbiologically stable from the first week in actual production conditions.


Serotonin depletion in the adult rat produces differential changes in highly polysialylated form of neural cell adhesion molecule and tenascin-C immunoreactivity.
Levels of immunoreactivity for highly polysialylated neural cell adhesion molecule (PSA-NCAM), NCAM, and tenascin-C (TN-C), were examined in the basal ganglia regions and hypothalamic nuclei of adult rats after serotonergic (5-HT) lesions induced by 5,7-dihydroxytryptamine injections in the dorsal and medial raphe nuclei. Decreases in the density of serotonin fibers were associated with no changes in NCAM and general decreases in PSA-NCAM staining, the time-course of changes being selective for each region. Taken that the confocal analysis indicated that serotonin neurons do not express PSA-NCAM and that similar decreases in PSA-NCAM staining were observed after inhibition of 5-HT synthesis induced by parachlorophenylalanine administration, these results suggest that 5-HT may reduce adhesion by acting on PSA-NCAM expression in its environment, and thus facilitate plasticity in adult brain. Two months after the neurotoxin lesions, a normalization of PSA-NCAM staining was associated with a partial restoration in 5-HT fiber density in the nucleus accumbens and the supraoptic nucleus, suggesting that PSA-NCAM may facilitate sprouting of 5-HT fibers. Since a similar normalization was also detected in the suprachiasmatic nucleus, which remained deprived of serotonin fibers, negative factors are likely to be involved in regeneration processes. Indeed, increases in glial fibrillary acidic protein (GFAP) followed by increases in TN-C were observed in these areas, suggesting that the secretion of TN-C by astrocytes may have negative consequences on the sprouting of 5-HT fibers. Finally, the lack of changes in striatal PSA-NCAM or TN-C staining observed after selective lesions of the dopaminergic pathway induced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity.


Ultrasound image-guided therapy enhances antitumor effect of cisplatin.
The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.


Short-term transdermal estradiol enhances nitric oxide synthase III and estrogen receptor mRNA expression in arteries of women with coronary artery disease.
To analyze the short-term effects of estradiol (E2) on the expression of nitric oxide synthase (NOS III) and estrogen receptors (ER) alpha and beta. We studied 20 post-menopausal women with coronary artery disease (CAD) undergoing CABG surgery with left internal mammary artery (LIMA) grafting. Ten women received treatment with transdermal E2 prior to surgery (48-72 h) and 10 did not. The distal segment of the LIMA was excised and processed to determine mRNA expression of NOS III and ER alpha and beta (RT-PCR). Expression of NOS III and ER alpha and beta was measured in arbitrary densitometric units (ADUs) relative to GPdH expression, constitutively expressed in human vessels. NOS III and ER alpha and beta mRNA expression was enhanced in women treated with E2 as compared to the control group (NOS III: 1.69+/-0.61 versus 1.14+/-0.48 ADUs, p=0.04; ER alpha: 6.52+/-6.80 versus 1.83+/-1.22 ADUs, p=0.04; ER beta: 4.20+/-3.42 versus 1.56+/-0.59 ADUs, p=0.03). ER alpha, but not ER beta expression, correlated with NOS III expression (r=0.70, p<0.001). After treatment with E2, NOS III, ER alpha, and ER beta mRNA expression was enhanced in arterial vessels of postmenopausal women with CAD. NOS III mRNA expression was only correlated to ER alpha expression, suggesting that NOS III activation could be more mediated by ER alpha.


[Spinal osteochondroma: diagnostic imaging and treatment. Case reports].
Osteochondromas are benign bony tumours, with only 1 to 4% being located in the spine. It occurs more frequently in the cervical spine, with C2 being the vertebra most affected. The neurological presentation is slow due to the growth characteristics of the tumour. Computed axial tomography is the reference method for diagnosis. Surgical management is indicated for patients with neurological impairment or pain. The first case presents a 21-year-old male with osteochondroma located in the spinous processes of L2, L3 and L4. The second case is a 20-year-old female with multiple osteochondromatosis with tumours at the right lateral mass of C1, with extension to C2 and tumours on the spinous processes of C5 and C7. Both patients presented with painful symptoms, which were resolved after surgical resection of the tumours. The rarity of these conditions, relevance of a clinical-radiographic diagnosis, and considerations required for surgical treatment are discussed here.


Effect of Hordei Fructus Germinatus on differential gene expression in the prolactin signaling pathway in the mammary gland of lactating rats.
In China, Hordei Fructus Germinatus (HFG) is the germinated and dried fruit of Hordeum vulgare L, which is commonly used in clinical Chinese medicine. Traditional Chinese Medicine (TCM) theory holds that HFG can be both medicinal and edible, which means that it is derived from food medicine. Raw HFG and roasted HFG are used to treat hypogalactia, hyperprolactinemia and indigestion. In recent years, the lactogenic and galactophygous effects of HFG have attracted increasing attention. Nevertheless, there is much confusion over the use of raw and processed HFG, and the mechanism of its lactogenic effect seems remains poorly understood. This study aimed to explore the lactogenic effect of raw HFG and roasted HFG on rats with overloaded lactation and to reveal the underlying molecular mechanism. Raw and processed HFG water decoctions were given to overloaded lactation model rats at a dose of 1.7800 g kg-1·d-1, and the control group was given the same volume of water. The lactogenic effect of raw and processed HFG was evaluated by measuring daily lactation, body weight and pup body weight, serum PRL, E2, and GH contents after parturition, and the pathological characteristics of mammary tissue sections. cDNA microarrays can be used to screen diverse gene expression patterns and signaling pathways related to prolactin. The expression of relevant differentially expressed genes was verified by real-time PCR and western blotting. In vivo experiments demonstrated that the raw HFG water decoction stimulated mammogenesis, accelerated the transformation of the lobular acinar system, resulted in denser mammary epithelial cells and thicker glandular ducts that were full of milk and facilitated the secretion of milk. Moreover, HFG increased PRL, E2, and GH levels, pup body weight, daily lactation and the body weight of lactating rats. Following gene chip identification, KEGG pathway enrichment analysis revealed genes that were highly related to prolactin in the prolactin signaling pathway and JAK-STAT signaling pathway, and the main differentially expressed genes were Jak2 (down), Stat5α (up), cyclin D1 (up), SOCS1 (up), CISH (down) and PRLR (up). Compared with the control group, RT-PCR results indicated that Jak2 and CISH were downregulated and that Stat5α, cyclin D1, SOCS1 and PRLR were upregulated. Western blot assays showed that PRLR, STAT5α and cyclin D1 levels in the mammary glands of the raw HFG water decoction group were significantly increased, which was consistent with the results of cDNA microarray screening. The present study reveals that raw HFG effectively enhances lactation in rats, possibly by influencing the prolactin/JAK-STAT signaling pathway.


Optical density of human macular pigment.
Foveal and parafoveal spectral sensitivities of the G cone mechanism were used to derive the difference spectrum for the macular pigment for 12 observers. Measurements of the peak density of the macular pigment were obtained with a shortened version of the same procedure for an additional 15 observers. The mean density for all 27 observers at 460 nm was 0.77 +/- 0.06 with a range of 0.21-1.22. The mean density is higher than that previously reported and, compared to the standard absorbance curve (Wyszecki and Stiles, 1967), the results indicate higher density values for wavelengths on the long wavelength side of the absorption maximum.


Thermochemical conversion pathways of Kappaphycus alvarezii granules through study of kinetic models.
Kappaphycus alvarezii seaweed belongs to the class of red alga (Rhodophyta). The granules obtained after recovery of "sap" (liquid plant stimulant) from freshly harvested alga is a promising biomass feedstock for energy application. Herein we report the kinetic behaviour of the granules using thermogravimetric analysis (TGA) at different heating rates in N2 atmosphere and thermogravimetric-mass spectrometry (TG-MS) analysis. Sawdust as lignocellulosic biomass is considered for comparative study. Four different kinetic models (i) multilinear regression technique, (ii) Friedman method, (iii) Flynn-Wall-Ozawa (FWO) method and (iv) Kissinger-Akahira-Sunose (KAS) method are used to evaluate the apparent activation energy (Ea), the pre-exponential factor (Aα) and the overall reaction order (n). Maximum SO2 peak at 300°C and 950°C (from TG-MS), indicates that slow pyrolysis at 500°C, with a packed bed lime scrubber at the outlet during temperature rise, is the best suited thermochemical pathway for energy harnessing.


First-principles study of the crystal and magnetic structures of multiferroic Cu2OCl2.
Recently, the discovery of multiferroicity in pyrochlore-like compound Cu2OCl2has generated significant interest, and several studies have been performed in this area. This transition metal oxychloride is unique because the divalent copper atoms create anS=1/2correlated insulator and the pyrochlore lattice tends to frustrate spins. From neutron powder diffraction measurements, an incommensurate magnetic order of the ordering vectorq=(0.827,0,0)emerges below the Néel temperature of 70 K. At this temperature or slightly above, ferroelectricity (FE) or antiferroelectricity, accompanying a lattice distortion, has been observed. Experimentally, some discrepancies remain. In this paper, we report our first-principles simulation results by evaluating the possible lattice and spin spiral states. We found that theFdddstructure is not more stable thanFdd2(a), which is supported by our reexamination of the x-ray diffraction data. In addition, we find that after we include magnetism in the calculation, it predicts that theFdd2(a)lattice with a helical (proper screw) spin structure is energetically more stable than other spin configurations. Our results indicate charge-order-driven FE that subsequently induces magnetism.


Network analysis of mood symptoms in adolescents with or at high risk for bipolar disorder.
Network analyses of psychopathology examine the relationships between individual symptoms in an attempt to establish the causal interactions between symptoms that may give rise to episodes of psychiatric disorders. We conducted a network analysis of mood symptoms in adolescents with or at risk for bipolar spectrum disorders. The sample consisted of 272 treatment-seeking adolescents with or at high risk for bipolar disorder who had at least subsyndromal depressive or (hypo)manic symptoms. Based on symptom scores assessed via semi-structured interviews, we constructed the network of depressive and manic symptoms and identified the most central symptoms and symptom communities within the network. We used bootstrapping analyses to determine the reliability of network parameters. Symptoms within the depressive and manic mood poles were more related to each other than to symptoms of the opposing mood pole. Four communities were identified, including a depressive symptom community and three manic symptom communities. Fatigue and depressed mood were the strongest individual symptoms within the overall network (ie the most highly correlated with other symptoms), followed by motor hyperactivity. Mood lability and irritability were found to be "bridge" symptoms that connected the two mood poles. Symptoms of activity/energy (ie fatigue and hyperactivity) and depressed mood are the most prominent mood symptoms among youth with bipolar spectrum disorders. Mood lability and irritability represent potential warning signs of emergent episodes of either polarity. Targeting these central and bridge symptoms would lead to more efficient assessments and therapeutic interventions for bipolar disorder.


Underwater endoscopic mucosal resection for rectal neuroendocrine tumors (with videos): a single center retrospective study.
Underwater endoscopic mucosal resection (UMER) is a new method of endoscopic resection to completely remove the lesion without submucosal injection. But few attempts have been carried out for rectal neuroendocrine tumors (rectal NETs). We retrospectively investigated data on the tumor characteristics and outcomes of patients with ≤ 10 mm rectal NETs who underwent UEMR or endoscopic submucosal dissection (ESD) from January 2019 to June 2021 in our institute. The endoscopic resection rate was 100% in both UEMR and ESD groups. The histological complete resection rate of the UEMR group (95.5%) was lower than that of the ESD group (96.4%) with no significant difference. The average operation time, hospitalization time and operation cost of UEMR group were less than those of ESD group (P < 0.05). The incidence of postoperative abdominal pain and abdominal distention in the UEMR group was lower than that in the ESD group (P < 0.05). There was no significant difference in the incidence of delayed bleeding and perforation between the two groups. There was no local recurrence or distant metastasis in the two groups during the follow-up period. Both the UEMR and ESD can effectively treat ≤ 10 mm rectal NETs with invasion depth confined to the mucosa and submucosa. UEMR is superior to ESD in operation time, hospitalization time, operation cost, postoperative abdominal pain and abdominal distention.


Diminished myelin-specific T cell activation associated with increase in CTLA4 and Fas molecules in multiple sclerosis patients treated with IFN-beta.
Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.


Partner aggressive women: characteristics and treatment attrition.
The topic of female partner aggression has been controversial for over 20 years, and yet we lack a coherent body of literature that describes the phenomenon. Furthermore, we know little about what treatment approaches effectively reduce partner aggression in women. Data for this study were derived from the initial evaluations of 107 domestically violent, heterosexual women referred to an anger management program. Descriptive statistics were used to expand our knowledge of the characteristics of this population. In addition, a number of variables were analyzed to determine their relevance to treatment dropout. Overall, women tended to be socioeconomically disadvantaged and undereducated, with histories of childhood attachment disruptions and victimization, mental health problems, and substance abuse. Participants that had been court mandated were more likely to complete treatment, while nonmandated women had fewer pretreatment arrests and were more likely to drop out after the initial intake. The implications for treatment are discussed, and suggestions for further investigation are offered.


Quantitative Evidence for the Dependence of Highly Crystalline Single Wall Carbon Nanotube Synthesis on the Growth Method.
We present a study quantitatively demonstrating that the method of synthesis (gas phase, fixed bed, non-fixed bed) represents a determining factor in the level of crystallinity in growing single wall carbon nanotubes (SWCNTs). Using far infrared spectroscopy, the "effective length" (associated with the level of crystallinity) was estimated for CNTs grown using various synthetic methods (lab-produced and supplemented by commercially purchased SWCNTs) as a metric for crystallinity (i.e., defect density). Analysis of the observed "effective lengths" showed that the SWCNTs fell into two general groups: long and short (high and low crystallinity) synthesized by gas-phase methods and all other supported catalyst methods, respectively. Importantly, the "long" group exhibited effective lengths in the range of 700-2200 nm, which was greater than double that of the typical values representing the "short" group (110-490 nm). These results highlight the significant difference in crystallinity. We interpret that the difference in the crystallinity stemmed from stress concentration at the nanotube-catalyst interface during the growth process, which originated from various sources of mismatch in growth rates (e.g., vertically aligned array) as well as impact stress from contact with other substrates during fluidization or rotation. These results are consistent with well-accepted belief, but now are demonstrated quantitatively.


Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?
Recent advances in the small field of the rare mixed phenotype acute leukemias (MPAL) are presented focusing on a better understanding of their pathophysiology and search for better therapeutic approaches. Three aspects of respective classification, therapy, and immunophenotype of MPAL are reviewed. New proposals have been made to segregate MPAL subtypes based on their genomic landscape. In parallel, it was found that a large array of therapeutic approaches has been tested in the past few years with increasingly good results. Finally, we explored the use of unsupervised flow cytometry analysis to dissect subtle variations in markers expression to better characterize the variegating aspect of MPALs. Genomic and immunophenotypic aspects more clearly link MPAL subtypes with bona fide acute myeloblastic of lymphoblastic leukemias. This is likely to impact therapeutic strategies, towards a better management and outcome.


Exposed tibial bone after burns: Flap reconstruction versus dermal substitute.
A 44 years old male patient had suffered extensive 3rd degree burns on both legs, undergoing thorough surgical debridement, resulting in both tibias being exposed. Approximately 5 months after the incident he was referred to the Department of Plastic and Reconstructive Surgery of the University Hospital Gent, Belgium, to undergo flap reconstruction. Free flap surgery was performed twice on both lower legs but failed on all four occasions. In between flap surgery, a dermal substitute (Integra(®)) was applied, attempting to cover the exposed tibias with a layer of soft tissue, but also without success. In order to promote the development of granulation tissue over the exposed bone, small holes were drilled in both tibias with removal of the outer layer of the anterior cortex causing the bone to bleed and subsequently negative pressure wound therapy (NPWT) was applied. The limited granulation tissue resulting from this procedure was then covered with a dermal substitute (Glyaderm(®)), consisting of acellular human dermis with an average thickness of 0.25mm. This dermal substitute was combined with a NPWT-dressing, and then served as an extracellular matrix (ECM), guiding the distribution of granulation tissue over the remaining areas of exposed tibial bone. Four days after initial application of Glyaderm(®) combined with NPWT both tibias were almost completely covered with a thin coating of soft tissue. In order to increase the thickness of this soft tissue cover two additional layers of Glyaderm(®) were applied at intervals of approximately 1 week. One week after the last Glyaderm(®) application both wounds were autografted. The combination of an acellular dermal substitute (Glyaderm(®)) with negative pressure wound therapy and skin grafting proved to be an efficient technique to cover a wider area of exposed tibial bone in a patient who was not a candidate for free flap surgery. An overview is also provided of newer and simpler techniques for coverage of exposed bone that could question the universal plastic surgery paradigm that flap surgery is the only way to cover these defects.


Paenibacillus polymyxa NMA1017 as a potential biocontrol agent of Phytophthora tropicalis, causal agent of cacao black pod rot in Chiapas, Mexico.
Cacao represents an important source of income for farmers in the south of Mexico. However, phytosanitary problems have disrupted the production over the years. The use of antagonistic microorganisms as biocontrol agents might improve the production of cacao. In this study, Paenibacillus polymyxa NMA1017, isolated from the rhizosphere of Opuntia ficus-indica L., was used as a biocontrol agent for black pod rot of Theobroma cacao L. cultivated in Chiapas, Mexico. The experiments were carried in vitro and in vivo using pear fruit (Pyrous communis) as model and cacao pods in the field, respectively. The effect of NMA1017 on the phytopathogen was observed by electron microscopy and the production of enzymes was tested as a potential mechanism of action. The bacterium inhibited the radial growth of Phytophthora tropicalis PtCa-14 by 85.9 ± 0.12%. The strain NMA1017 affected mycelial development, as observed by the damage to the cell wall of the oomycete. In pear fruit, the biocontrol agent controlled the production of mycelium on the pear fruit surface, indicating an inhibitory effect exerted. Cacao pods infected with P. tropicalis in the field resulted in a reduction in disease incidence from 86 to 33% and in infection from 68 to 6%. Moreover, strain NMA1017 produced hydrolytic enzymes such as cellulases, xylanases, chitinases and proteases. The results obtained highlight P. polymyxa NMA1017 as an organism of interest for the biocontrol of P. tropicalis, as a method to rescue this important crop in Mexico.


Combination therapy with an aminoglycoside for Staphylococcus aureus endocarditis and/or persistent bacteremia is associated with a decreased rate of recurrent bacteremia: a cohort study.
Although limited data exist on the efficacy and potential risk of synergistic aminoglycoside therapy for persistent Staphylococcus aureus bacteremia and endocarditis, aminoglycosides are frequently used in clinical practice. As our study population, we included subjects fulfilling the modified Duke criteria for S. aureus endocarditis and/or having greater than 72 h of S. aureus bacteremia. Among these subjects, we compared patients who did and did not receive aminoglycoside therapy for their S. aureus bloodstream infection. These groups were compared for the primary outcome of recurrent bacteremia, as well as for the duration of bacteremia, mortality, complication rate, and incident renal failure. Eighty-seven subjects fulfilled the inclusion criteria. Of these, 49 received aminoglycoside therapy, whereas 38 did not. There were no significant differences in the baseline characteristics when comparing groups who did or did not receive aminoglycoside therapy. Four (8.2%) subjects treated with aminoglycoside therapy experienced recurrent bacteremia versus nine (23.7%) who did not receive aminoglycoside therapy [relative risk and 95% confidence interval [RR (95%CI)] = 0.51 (0.22-1.17), p = 0.04]. In multivariable analyses, aminoglycoside use remained significantly associated with a decrease in recurrent bacteremia [adjusted odds ratio (OR) (95%CI) = 0.26 (0.07-0.98), p = 0.046]. No significant differences were seen between groups treated with and without an aminoglycoside in terms of the 6-month all-cause mortality (51.0 vs. 42.1%, p = 0.41), complication rate (71.4 vs. 73.7%, p = 0.82), or incident renal failure (54.5 vs. 46.9%, p = 0.54). The use of combination therapy with an aminoglycoside in persistent S. aureus bacteremia and/or endocarditis may be associated with a lower rate of recurrent bacteremia without significant differences in the incident renal failure.


Immunochemical detection of nitric oxide and nitrogen dioxide trapping of the tyrosyl radical and the resulting nitrotyrosine in sperm whale myoglobin.
We demonstrate herein that nitric oxide (*NO) and nitrogen dioxide (*NO2) both react with the tyrosyl radical formed in sperm whale myoglobin (swMb) by reaction with hydrogen peroxide. The tyrosyl radical was detected by Western blotting using a novel anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that specifically recognizes protein radical-derived DMPO nitrone adducts. In the presence of DMPO, hydrogen peroxide reacts with swMb to form the DMPO tyrosyl radical as is known from both electron spin resonance and immuno-spin trapping investigations. Both *NO and NO2- significantly suppressed DMPO-Mb formation under the physiological oxygen tension of 30 mm Hg. If this inhibition of DMPO trapping of the tyrosyl radical is due, at least in part, to the reaction of the tyrosyl radical with *NO and *NO2, then nitrotyrosine should be formed. In line with this expectation, swMb treated with low concentrations of *NO or NO2- formed nitrotyrosine when hydrogen peroxide was added under 30 mm Hg oxygen tension as detected by Western blotting. The amount of nitrotyrosine generated with *NO was higher than with NO2-, implying that there are two different peroxynitrite-independent nitrotyrosine formation mechanisms and that *NO is not just a source of *NO2.


Comparison of oblique versus hockey-stick surgical incision for kidney transplantation.
The hockey-stick surgical incision is becoming more popular than the oblique incision for kidney transplantations. Both incisions are convenient and comfortable. Both have some drawbacks, such as muscle denervation for the former, or section of lateral muscles for the latter. In this retrospective study, we compared these incisions with regard to the incidence of long-term complications, such as postincisional hernia, relaxation of the abdominal wall, and a poor cosmetic result. One hundred patients (50 of each type) were evaluated at an average of 4.5 years after transplantation (3 months-15 years). Occurrence of incisional hernia was 16% in the former (8 cases) versus 4% in the latter (2 cases: X(2) = 4; P < .05). A major relaxation of the abdominal wall was found in 24% of the former (12 cases) versus 8% of the latter (4 cases) (X(2) = 4.76; P < .05). These complications were not correlated with age, sex, weight, side of transplant, or immunosuppressive drugs. In the former patients with hockey-stick incisions, the overall cosmetic results were poor, because in most cases the incision had been prolonged upward, above the transverse umbilical line, even as high as the costal arch. In 20% of the former patients with hockey-stick incisions, the scar had widened, particularly in the upper vertical branch of the J incision. We conclude that the final outcome of the oblique surgical incision was better than the hockey-stick incision because of the lower incidence of hernia and abdominal wall relaxation and the more favorable cosmetic results.


Monoterpene indole alkaloids from Melodinus cochinchinensis (Lour.) Merr.
Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7).


Ecology of a leaf color polymorphism in a tropical forest species: habitat segregation and herbivory.
Byttneria aculeata (Sterculiaceae), a subcanopy liane with a shrubby juvenile form has two distinct leaf color morphs in juvenile plants- a given juvenile has plain green leaves or leaves with whitish variegation. Both forms occur together in the forest and in clearings; however, the variegated morph is more common in open sites, and the plain morph predominates in the forest. Percent variegation per leaf for variegated plants increased from closed to open sites. Measurements of growth support the idea that variegation is favored in open habitats. Within a given habitat, rate of herbivory by leaf miners on a given morph increases with increasing relative frequency of that morph; however, at a given relative frequency, the variegated morph is less heavily attacked than is the plain morph when it occurs elsewhere at that same frequency.


Personalized prescription of tyrosine kinase inhibitors in unresectable metastatic cholangiocarcinoma.
Cholangiocarcinoma is an aggressive tumor with poor prognosis. Most of the cases are not available for surgery at the stage of the diagnosis and the best clinical practice chemotherapy results in about 12-month median survival. Several tyrosine kinase inhibitors (TKIs) are currently under investigation as an alternative treatment option for cholangiocarcinoma. Thus, the report of personalized selection of effective inhibitor and case outcome are of clinical interest. Here we report a case of aggressive metastatic cholangiocarcinoma (MCC) in 72-year-old man, sequentially treated with two targeted chemotherapies. Initially disease quickly progressed during best clinical practice care (gemcitabine in combination with cisplatin or capecitabine), which was accompanied by significant decrease of life quality. Monotherapy with TKI sorafenib was prescribed to the patient, which resulted in stabilization of tumor growth and elimination of pain. The choice of the inhibitor was made based on high-throughput screening of gene expression in the patient's tumor biopsy, utilized by Oncobox platform to build a personalized rating of potentially effective target therapies. However, time to progression after start of sorafenib administration did not exceed 6 months and the regimen was changed to monotherapy with Pazopanib, another TKI predicted to be effective for this patient according to the same molecular test. It resulted in disease progression according to RECIST with simultaneous elimination of sorafenib side effects such as rash and hand-foot syndrome. After 2 years from the diagnosis of MCC the patient was alive and physically active, which is substantially longer than median survival for standard therapy. This case evidences that sequential personalized prescription of different TKIs may show promising efficacy in terms of survival and quality of life in MCC.


Lebecetin, a snake venom C-type lectin protein, modulates LPS-induced inflammatory cytokine production in human THP-1-derived macrophages.
The excessive production of inflammatory mediators results in an overactive immune response leading to the worsening of various human diseases. Thus, there is a still need to identify molecules able to regulate the inflammatory response. Lebecetin, a C-type lectin protein isolated from Macrovipera lebetina snake venom, was previously characterized as a platelet aggregation inhibitor and antitumor active biomolecule. In the present work, we investigated its effect on the production of some cytokines linked to inflammatory response and the underlying mechanisms in lipopolysaccharide (LPS)-induced THP1 macrophages. Interestingly, we found that lebecetin reduced the levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while it partially increased LPS-induced secretion of the immunomodulatory cytokine IL-10. Furthermore, this modulatory effect was accompanied by decreased activation of ERK1/2, p38, AKT kinases and NF-κB along with reduced expression of αvβ3 integrin. Thus, this study highlights the promising role of lebecetin as a natural biomolecule that could manage the inflammatory response involved in the development and progression of inflammatory diseases.


A comparison of 2 circuit exercise training techniques for eliciting matched metabolic responses in persons with paraplegia.
To test whether acute metabolic (VO(2)), chronotropic (heart rate), and perceptual (rating of perceived exertion; RPE) responses to exercise by persons with paraplegia differ when the exercise is on a multistation isoinertial exercise system (MultiGym) or on a customized system of Thera-Band resistance bands (ElasticGym). Within-subjects comparison of 2 treatments. Academic medical center. Sixteen men and 1 woman with complete paraplegia (T4-L1), as defined by the American Spinal Injury Association. A circuit resistance training (CRT) program for persons with paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises used for training and testing used 6 resistance maneuvers at 50% of the 1-repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were habituated to both conditions for 2 weeks before testing on randomized nonconsecutive days. VO(2) (L/min) was measured by portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by the Borg Scale of Perceived Exertion (6-20). No significant effects of test condition on average VO(2) or heart rate were observed, with differences between conditions reflecting only .08L/min and 6.4 beats/min, respectively. Average RPE was significantly higher in testing under the ElasticGym condition (P < .05). CRT on a customized ElasticGym system elicited acute metabolic and chronotropic responses that did not differ from responses to exercise on a MultiGym, though RPE was greater with the ElasticGym.


Joint effect of hostility and severity of depressive symptoms on plasma interleukin-6 concentration.
Although interleukin (IL)-6 plays a significant role in cardiovascular disease, little is known about its relation to psychological risk factors, such as hostility and severity of depressive symptoms. The current study examined the joint effects of severity of depressive symptoms and hostility on plasma IL-6 in a sample of 90 healthy, nonsmoking men. After an overnight fast, blood samples for plasma IL-6 and fasting lipids were collected on the same day that the Beck Depression Inventory (BDI) and the Cook-Medley hostility (Ho) scale were administered. Plasma IL-6 was determined using enzymatic-linked immunosorbent assay (ELISA). Analyses of logarithmically normalized plasma IL-6 adjusting for age, body mass index (BMI), fasting total cholesterol, high density lipoprotein (HDL), and resting diastolic blood pressure (DBP) revealed a significant BDI by Ho interaction (p =.026). Post hoc decomposition revealed that Ho was correlated with log-normalized plasma IL-6 (r = 0.59, p =.025) but only among men with BDI scores of 10 and above. Alternatively, BDI was correlated with log-normalized plasma IL-6 (r = 0.61, p =.003) but only among men with Ho scores of 23 and higher. Comparisons among BDI/Ho groups indicated that men with high scores on both the BDI and the Ho exhibited the highest median levels of plasma IL-6. Hostile men who exhibited above normal levels of depressive symptoms had higher plasma levels of IL-6 suggestive of a subpopulation at increased risk for future cardiac events.