Logistic regression over encrypted data from fully homomorphic encryption.
One of the tasks in the 2017 iDASH secure genome analysis competition was to enable training of logistic regression models over encrypted genomic data. More precisely, given a list of approximately 1500 patient records, each with 18 binary features containing information on specific mutations, the idea was for the data holder to encrypt the records using homomorphic encryption, and send them to an untrusted cloud for storage. The cloud could then homomorphically apply a training algorithm on the encrypted data to obtain an encrypted logistic regression model, which can be sent to the data holder for decryption. In this way, the data holder could successfully outsource the training process without revealing either her sensitive data, or the trained model, to the cloud. Our solution to this problem has several novelties: we use a multi-bit plaintext space in fully homomorphic encryption together with fixed point number encoding; we combine bootstrapping in fully homomorphic encryption with a scaling operation in fixed point arithmetic; we use a minimax polynomial approximation to the sigmoid function and the 1-bit gradient descent method to reduce the plaintext growth in the training process. Our algorithm for training over encrypted data takes 0.4-3.2 hours per iteration of gradient descent. We demonstrate the feasibility but high computational cost of training over encrypted data. On the other hand, our method can guarantee the highest level of data privacy in critical applications.


Nomogram for predicting cancer-specific survival in undifferentiated pleomorphic sarcoma: A Surveillance, Epidemiology, and End Results -based study.
The purpose of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in undifferentiated pleomorphic sarcoma (UPS) patients at 3, 5, and 8 years after the diagnosis. Data for UPS patients were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. The patients were randomly divided into a training cohort (70%) and a validation cohort (30%). The backward stepwise Cox regression model was used to select independent prognostic factors. All of the factors were integrated into the nomogram to predict the CSS rates in UPS patients at 3, 5, and 8 years after the diagnosis. The nomogram' s performance was then validated using multiple indicators, including the area under the time-dependent receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, decision-curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI). This study included 2,009 UPS patients. Ten prognostic factors were identified after analysis of the Cox regression model in the training cohort, which were year of diagnosis, age, race, primary site, histological grade, T, N, M stage, surgery status, and insurance status. The nomogram was then constructed and validated internally and externally. The relatively high C-indexes and AUC values indicated that the nomogram has good discrimination ability. The calibration curves revealed that the nomogram was well calibrated. NRI and IDI values were both improved, indicating that our nomogram was superior to the AJCC (American Joint Committee on Cancer) system. DCA curves demonstrated that the nomogram was clinically useful. The first nomogram for predicting the prognosis of UPS patients has been constructed and validated. Its usability and performance showed that the nomogram can be applied to clinical practice. However, further external validation is still needed.


The Variant rs145204276 of GAS5 is Associated with the Development and Prognosis of Gastric Cancer.
Down-regulation of the growth arrest specific transcript 5 (GAS5) (long non-coding RNA) is associated with cell proliferation of gastric cancer (GC) and a poor prognosis. We aimed to investigate whether the variant rs145204276 of GAS5 is associated with the prognosis of GC in the Chinese population, and to unveil the regulatory mechanism underlying the GAS5 expression in GC tissues. 1,253 GC patients and 1,354 healthy controls were included. The frequency of the genotype del/del and the allele del of rs145204276 were compared between the patients and the controls and between different subgroups of patients classified by clinicopathological variables. The overall survival rate was analyzed according to the Kaplan-Meier method using the log-rank test. The frequency of genotype del/del was significantly lower in patients than in the controls (7.0% vs. 9.1%, p = 0.001). Kaplan-Meier analysis showed that genotype del/del was significantly associated with a higher survival rate (p = 0.01). Patients with late tumor stage were found to have a significantly lower rate of genotype del/del than those with an early tumor stage (4.9% vs. 8.8%, p = 0.01). Patients with UICC III and IV were found to have a significantly lower rate of genotype del/del than those with UICC I and II (5.3% vs. 8.1%, p = 0.02). The variant rs145204276 of GAS5 is associated with the development and prognosis of GC. The allele del of rs145204276 is associated with a remarkably lower incidence of cancer progression and metastasis.


Medical student perceptions of radiology use in anatomy teaching.
The use of radiology in the teaching of anatomy to medical students is gaining in popularity; however, there is wide variation in how and when radiology is introduced into the curriculum. The authors sought to investigate students' perceptions regarding methods used to depict and teach anatomy and effects of integrated radiology instruction on students' abilities to correctly identify imaging modalities and anatomical structures on radiological images. First-year medical students completed questionnaires at the beginning and end of the first academic year that incorporated ten hours of radiologic anatomy teaching in the anatomy curriculum. Questions used a combination of Likert scales, rankings, and binary options. Students were tested on their ability to identify radiology modalities and anatomical structures on radiology images. Preresponse and postresponse rates were 93% (157/168) and 85% (136/160), respectively. Postmodule, 96.3% of students wanted the same or more radiology integration. Furthermore, 92.4% premodule and 96.2% postmodule agreed that "Radiology is important in medical undergraduate teaching." Modality and structure identification scores significantly increased from 59.8% to 64.3% (P < 0.001) and from 47.4% to 71.2% (P < 0.001), respectively. The top three preferred teaching formats premodule and postmodule were (1) anatomy laboratory instruction, (2) interactive sessions combining radiology with anatomy, and (3) anatomy lectures. Postmodule, 38.3% of students were comfortable reviewing radiology images. Students were positive about integrating radiology into anatomy teaching and most students wanted at least the same level of assimilation but that it is used as an adjunct rather than primary method of teaching anatomy.


Expression of cathepsins S and D signals a distinctive biochemical trait in CD34+ hematopoietic stem cells of relapsing-remitting multiple sclerosis patients.
The elucidation of mechanistic aspects of relapsing-remitting multiple sclerosis (RRMS) pathogenesis may offer valuable insights into diagnostic decisions and medical treatment. Two lysosomal proteases, cathepsins S and D (CatS and CatD), display an exclusive pattern of expression in CD34(+) hematopoietic stem cells (HSCs) from peripheral blood of acute MS (A-MS) patients (n = 20). While both enzymes normally exist as precursor forms in the HSCs of healthy individuals (n = 30), the same cells from A-MS patients consistently exhibit mature enzymes. Further, mature cathepsins are expressed at lower rates in stable MS subjects (S-MS, n = 15) and revert to precursor proteins after interferon-β1a treatment (n = 5). Mature CatD and CatS were induced in HSCs of healthy donors that were either co-cultured with PBMCs of A-MS patients or exposed to their plasma, suggesting a functional involvement of soluble agents. Following HSC exposure to several cytokines known to be implicated in MS, and based on relative cytokine levels displayed in A-MS, S-MS and control individuals, we identified IL-16 as a specific cell signaling factor associated with cathepsin processing. These data point to an evident correlation between CatS and CatD expression and MS clinical stage, and define a biochemical trait in HSCs with functional, medical, and diagnostic relevance.


Trajectories of alcohol use and consequences in college women with and without depressed mood.
College students with depressed mood face heightened risk for experiencing drinking-related negative consequences. However, few studies have examined prospective patterns of alcohol consequences among depressed students. In the present investigation, we assessed how first-year college women's trajectories of heavy episodic drinking (HED) and alcohol consequences differed as a function of depressed mood at college entry. Participants were 233 heavy drinking incoming first-year college females (61% White) at a mid-sized West Coast University. Participants completed an online baseline survey, attended a single brief group intervention session, and completed 1- and 6-month post-intervention follow-up surveys. Depressed mood, alcohol consumption, and alcohol consequences were assessed at each time point. We employed latent growth curve analyses. Females with depressed mood, versus without depressed mood, experienced greater levels of alcohol consequences overall, particularly during transitions to college. However, contrary to hypotheses, participants with depressed mood (vs. without) exhibited significantly steeper declining trends in consequences, controlling for treatment condition, age, race, and ethnicity, and despite stable drinking levels, depressed mood, and use of protective behaviors over time. Potential explanations and suggestions for future research are discussed.


Comparison of Hydrogel-Based Autologous Chondrocyte Implantation Versus Microfracture: A Propensity Score Matched-Pair Analysis.
Few studies exist for large defects comparing matrix-associated autologous chondrocyte implantation (M-ACI) with other cartilage repair methods due to the limited availability of suitable comparator treatments. To compare the clinical efficacy of a novel hydrogel-based M-ACI method (NOVOCART Inject plus) versus microfracture (MFx) in patients with knee cartilage defects. Cohort study; Level of evidence, 3. Propensity score matched-pair analysis was used to compare the 24-month outcomes between the M-ACI treatment group from a previous single-arm phase 3 study and the MFx control group from another phase 3 study. Patients were matched based on preoperative Knee injury and Osteoarthritis Outcomes Score (KOOS), symptom duration, previous knee surgeries, age, and sex, resulting in 144 patients in the matched-pair set (72 patients per group). The primary endpoint was the change in least-squares means (ΔLSmeans) for the KOOS from baseline to the 24-month assessment. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 versus 3.7 cm2). Other differences included defect location (no patellar or tibial defects in the MFx group), number of defects (33.3% with 2 defects in the M-ACI group versus 9.7% in the MFx group), and defect cause (more patients with degenerative lesions in the M-ACI group). The M-ACI group had higher posttreatment KOOS (M-ACI versus MFX: 81.8 ± 16.8 versus 73.0 ± 20.6 points) and KOOS ΔLSmeans from baseline to 24 months posttreatment (M-ACI versus MFX: 36.9 versus 26.9 points). Treatment contrasts in KOOS ΔLSmeans from baseline indicated statistical significance in favor of M-ACI from 3 to 24 months posttreatment (P = .0026). Significant and clinically meaningful differences in favor of M-ACI at 24 months were also found regarding International Knee Documentation Committee (IKDC) score ΔLSmeans from baseline (37.8 versus 30.4 points; P = .0334), KOOS responder rates at 24 months (≥10-point improvement from baseline; 94.4% versus 65.3%; P < .0001), IKDC responder rates at 24 months (>20.5-point improvement from baseline; 83.3% versus 61.1%, P = .0126) and MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in a subgroup of patients (LS means, 86.9 versus 69.1; P = .0096). In this exploratory analysis, M-ACI using an in situ crosslinked hydrogel demonstrated superior clinical and structural (MOCART) 24-month outcomes compared with MFx in patients with knee cartilage defects.


Nuclear transfer with apoptotic bovine fibroblasts: can programmed cell death be reprogrammed?
Cell death by apoptosis is considered to be irreversible. However, reports have indicated that its reversibility is possible if the cells have not yet reached the "point of no return." In order to add new information about this topic, we used cells at different moments of apoptotic process as nuclear donors in somatic cell nuclear transfer (SCNT) in order to test if programmed cell death can be reversed. Adult bovine fibroblasts were treated with 10 μM of staurosporine (STP) for 3 h and analyzed for phosphatidylserine externalization (Annexin assay) and presence of active caspase-9. Annexin-positive (Anx+) and Caspase-9-positive (Casp-9+) cells were isolated by FACS and immediately transferred into enucleated in vitro matured bovine oocytes. After STP treatment, 89.9% of cells were Anx+ (4.6% in control cells; p<0.01) and 24.9% were Casp-9+ (2.4% in control cells; p<0.01). Fusion and cleavage were not affected by the use apoptotic cells (p>0.05). Also, the use of Anx+ cells did not affect blastocyst production compared to control (26.4% vs. 22.9%, respectively; p>0.05). However, blastocyst formation was affected by the use of Casp-9+ cells (12.3%; p<0.05). These findings contribute to the idea of that apoptosis is reversible only at early stages. Additionally, we hypothesize that the "point of no return" for apoptosis may be located around activation of Caspase-9.


Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I.
We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and glutamate through a microdialysis probe stereotaxically implanted into the cerebellar cortex and deep cerebellar nuclei greatly depressed the release of gamma-aminobutyric acid (GABA), which normally follows a glutamate pulse. This inhibition was dose-dependent and long-lasting. Moreover, the effect was specific for glutamate since KCl-induced GABA release was not modified by IGF-I. Basic fibroblast growth factor, another growth-related peptide present in the cerebellum, did not alter the response of GABA to glutamate stimulation. In addition, electrical stimulation of the inferior olivary complex significantly raised IGF-I levels in the cerebellar cortex. Interestingly, when the inferior olive was stimulated in conjunction with glutamate administration, GABA release by cerebellar cells in response to subsequent glutamate pulses was depressed in a manner reminiscent of that seen after IGF-I. These findings indicate that IGF-I produces a long-lasting depression of GABA release by Purkinje cells in response to glutamate. IGF-I might be present in climbing fiber terminals and/or cells within the cerebellar cortex and thereby might affect Purkinje cell function. Whether this IGF-I-induced impairment of glutamate stimulation of Purkinje cells underlies functionally plastic processes such as long-term depression is open to question.


Effect of Pleuran (β-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes.
Excessive and exhausting physical loads depress the immune system. Carbohydrate consumption may minimize the postexercise suppression of the innate immune system. β-Glucan is a well-known immunomodulator, with positive effects on the functioning of immunocompetent cells. The goal of this study was to determine whether β-glucan dietary supplementation from the mushroom Pleurotus ostreatus decreases the suppressed immune system responses induced by short-term high-intensity exercise in humans. In this double-blind pilot study, 20 elite athletes were randomized to β-glucan (n = 9) or placebo (n = 11) groups; these groups consumed 100 mg of β-glucan (Imunoglukan) or placebo supplements, respectively, once a day for 2 months. Venous whole blood was collected before and after 2 months of supplementation (baseline), both immediately and 1 h after (recovery period) a 20-min intensive exercise bout at the end of the supplementation period. The blood samples were used to measure the cell counts of leukocytes, erythrocyte, and lymphocytes; subpopulations of lymphocytes, granulocytes, and monocytes; and natural killer (NK) cell activity (NKCA). A 28% reduction in NKCA (p < 0.01) below the baseline value was observed in the placebo group during the recovery period, whereas no significant reduction in NKCA was found in the β-glucan group. In addition, no significant decrease in NK cell count was measured in the β-glucan group during the recovery period. Immune cell counts did not differ significantly between the groups. These results indicate that insoluble β-glucan supplementation from P. ostreatus may play a role in modulating exercise-induced changes in NKCA in intensively training athletes.


Giant vulvar lymphangioma circumscriptum mimicking vulvar tumor: a case report and literature review.
Lymphangioma circumscriptum (LC) is a benign dilation of lymph channels localized to the skin and subcutaneous tissues. Primary vulvar involvement is very rare, with only 34 cases reported. A 17-year-old girl presented with pain and an 18-cm mass of the right labium majus that started 4 years earlier. She underwent wide local excision, and histological examination showed multiple dilated vascular channels in papillary dermis with a diagnosis of vulvar LC. Vulvar lymphangioma may mimic other vulvar tumors. Excision may be the best treatment of extensive vulvar LC.


Two-beam interferometer with optical path difference magnified.
A two-beam interferometer is proposed and experimentally demonstrated with OPD magnified. Two cascaded fiber ring resonators with almost the same fiber length are spliced into a fiber loop. An acousto-optic modulator is employed to generate optical pulses and to choose the pulses traveling around one of the resonators for x trips. The interferometer is characterized in displacement in our experiment. Experimental results show the proportional relationship between the sensitivity and x. The high-sensitivity interferometer scheme is useful in some measurement applications that require high sensitivity, such as solid earth tide gauge.


Carbon dioxide adsorption to UiO-66: theoretical analysis of binding energy and NMR properties.
UiO-66 is one of the most valuable metal-organic frameworks because of its excellent adsorption capability for gas molecules and its high stability towards water. Herein we investigated adsorption of carbon dioxide (CO2), acetone, and methanol to infinite UiO-66 using DFT calculations on an infinite system under periodic-boundary conditions and post-Hartree-Fock (SCS-MP2 and MP2.5) calculations on cluster models. Three to four molecules are adsorbed at each of four μ-OH groups bridging three Zr atoms in one unit cell (named Site I). Six molecules are adsorbed around three pillar ligands, where the molecule is loosely surrounded by three terephthalate ligands (named Site II). Also, six molecules are adsorbed around the pillar ligand in a different manner from that at Site II, where the molecule is surrounded by three terephthalate ligands (named Site III). Totally fifteen to sixteen CO2 molecules are adsorbed into one unit cell of UiO-66. The binding energy (BE) decreases in the order Site I > Site III > Site II for all three molecules studied here and in the order acetone > methanol ≫ CO2 in the three adsorption sites. At the site I, the protonic H atom of the μ-OH group interacts strongly with the negatively charged O atom of CO2, acetone and methanol, which is the origin of the largest BE value at this site. Although the DFT calculations present these decreasing orders of BE values correctly, the correction by post-Hartree-Fock calculations is not negligibly small and must be added for obtaining better BE values. We explored NMR spectra of UiO-66 with adsorbed CO2 molecules and found that the isotropic shielding constants of the 1H atom significantly differ among no CO2, one CO2 (at Sites I, II, or III), and fifteen CO2 adsorption cases (Sites I to III) but the isotropic 17O and 13C shielding constants change moderately by adsorption of fifteen CO2 molecules. Thus, 1H NMR measurement is a useful experiment for investigating CO2 adsorption.


A parametric approach to shape field-relevant blast wave profiles in compressed-gas-driven shock tube.
Detonation of a high-explosive produces shock-blast wave, shrapnel, and gaseous products. While direct exposure to blast is a concern near the epicenter, shock-blast can affect subjects, even at farther distances. When a pure shock-blast wave encounters the subject, in the absence of shrapnels, fall, or gaseous products the loading is termed as primary blast loading and is the subject of this paper. The wave profile is characterized by blast overpressure, positive time duration, and impulse and called herein as shock-blast wave parameters (SWPs). These parameters in turn are uniquely determined by the strength of high explosive and the distance of the human subjects from the epicenter. The shape and magnitude of the profile determine the severity of injury to the subjects. As shown in some of our recent works (1-3), the profile not only determines the survival of the subjects (e.g., animals) but also the acute and chronic biomechanical injuries along with the following bio-chemical sequelae. It is extremely important to carefully design and operate the shock tube to produce field-relevant SWPs. Furthermore, it is vital to identify and eliminate the artifacts that are inadvertently introduced in the shock-blast profile that may affect the results. In this work, we examine the relationship between shock tube adjustable parameters (SAPs) and SWPs that can be used to control the blast profile; the results can be easily applied to many of the laboratory shock tubes. Further, replication of shock profile (magnitude and shape) can be related to field explosions and can be a standard in comparing results across different laboratories. Forty experiments are carried out by judiciously varying SAPs such as membrane thickness, breech length (66.68-1209.68 mm), measurement location, and type of driver gas (nitrogen, helium). The effects SAPs have on the resulting shock-blast profiles are shown. Also, the shock-blast profiles of a TNT explosion from ConWep software is compared with the profiles obtained from the shock tube. To conclude, our experimental results demonstrate that a compressed-gas shock tube when designed and operated carefully can replicate the blast time profiles of field explosions accurately. Such a faithful replication is an essential first step when studying the effects of blast induced neurotrauma using animal models.


The impact of the major causes of death on life expectancy in China: a 60-year longitudinal study.
In the 12th Five-Year Plan, the Chinese government set the goal of increasing life expectancy by one year. The purpose of this study is to examine the impact of major causes of death on the life expectancy of the Chinese people between 1950 and 2010 and predict changing trends to identify major issues requiring future attention. A continuous database organised by population and death data on diseases by age group between 1950 and 2010 were created from A Province in Eastern China. The diseases were classified into four categories by the International Classification of Diseases-10 (ICD-10): infectious and parasitic diseases, chronic diseases, accidental injuries, and maternal diseases. Potential gains in life expectancy (PGLEs) were applied to reflect the impact on life expectancy caused by deaths from various diseases, by using the cause-eliminated life table. The PGLEs of infectious and parasitic diseases decreased from 15.59 years in 1950, to 0.07 year in 2010, and have remained low since 2000. However, the PGLEs of chronic diseases increased from 8.70 years in 1950, to 13.36 years in 2010, and indicated an increasing future trend. The two opposite trends exhibited a 'scissors-like difference'. The proportion of accidental injuries and maternal diseases in the death spectrum was low. The PGLEs of accidental injuries decreased from 2.95 years in 1950, to 0.86 year in 2010, maintaining a low level, while the PGLEs of maternal diseases dropped from 0.56 to 0.002 year during the same period, approaching zero. The findings of this study provide useful information, which could contribute to a more effective allocation of public health programmes. In recent years, chronic diseases and accidental injuries have emerged as major factors influencing life expectancy. Primary and secondary prevention actions, such as public education, modification of behaviours, and introduction of safety measures should be emphasised in efforts to promote life expectancy. The morbidity and mortality rates of infectious, parasitic, and maternal diseases should be maintained at low levels.


Assessing the epithelial-to-mesenchymal plasticity in a small cell lung carcinoma (SCLC) and lung fibroblasts co-culture model.
The tumor microenvironment (TME) is the source of important cues that govern epithelial-to-mesenchymal transition (EMT) and facilitate the acquisition of aggressive traits by cancer cells. It is now recognized that EMT is not a binary program, and cancer cells rarely switch to a fully mesenchymal phenotype. Rather, cancer cells exist in multiple hybrid epithelial/mesenchymal (E/M) states responsible for cell population heterogeneity, which is advantageous for the ever-changing environment during tumor development and metastasis. How are these intermediate states generated and maintained is not fully understood. Here, we show that direct interaction between small cell lung carcinoma cells and lung fibroblasts induces a hybrid EMT phenotype in cancer cells in which several mesenchymal genes involved in receptor interaction with the extracellular matrix (ECM) and ECM remodeling are upregulated while epithelial genes such as E-cadherin remain unchanged or slightly increase. We also demonstrate that several core EMT-regulating transcription factors (EMT-TFs) are upregulated in cancer cells during direct contact with fibroblasts, as is Yes-associated protein (YAP1), a major regulator of the Hippo pathway. Further, we show that these changes are transient and reverse to the initial state once the interaction is disrupted. Altogether, our results provide evidence that tumor cells' direct contact with the fibroblasts in the TME initiates a signaling cascade responsible for hybrid E/M states of cancer cells. These hybrid states are maintained during the interaction and possibly contribute to therapy resistance and immune evasion, while interference with direct contact will result in slow recovery and switch to the initial states.


Free vascularized fibular grafts: radiographic evidence of remodeling and hypertrophy.
A study was undertaken to determine the growth potential and radiographic appearance of a free vascularized fibular graft as it responds to the mechanical and physiologic features of its new environment. In a 10-year period, 30 patients underwent reconstruction of a large skeletal defect with a vascularized fibular graft. Radiographic studies were adequate for assessing sequential changes in 21 patients. Hypertrophy was evaluated by serial measurements of the periosteal and endosteal dimensions and was assessed with respect to age, sex, duration and location of the graft, the indication for reconstruction, and fixation apparatus. Hypertrophy of vascularized bone grafts is not rare. Among 21 vascularized fibular grafts, a measurable degree of hypertrophy was found in eight. Hypertrophy was caused by periosteal formation of new bone. The amount of hypertrophy could be considerable; in some cases it reached 2 cm of new cortical bone, resulting in an unusual radiographic appearance of marked cortical thickening. The amount of hypertrophy was greatest in young males, but was independent of diagnosis and site, and could be seen even in grafts bridged by metallic plates. Hypertrophy of vascularized bone grafts is a relatively frequent finding and has distinctive radiographic features. It is unclear why hypertrophy occurs to a much greater extent in some grafts than in others.


Preoperative evaluation of adult isthmic spondylolisthesis with diskography.
Fourteen consecutive patients with a diagnosis of isthmic spondylolisthesis (grade I and II) underwent provocative lumbar diskography (L2-S1) to evaluate the disk adjacent to the spondylolisthesis. Seven (50%) of 14 patients had concordant pain at the disk above the slip and 2 patients had no pain at the slip level. Surgical treatment included anteroposterior fusion of the slip level and any adjacent concordant levels. Clinical results included 3 excellent, 7 good, 2 fair, and 1 poor outcome. This data supports the hypothesis that the disk adjacent to an isthmic slip is predisposed to symptomatic degeneration in the adult patient with axial pain. It does not prove that a fusion is indicated or that clinical outcomes would be improved with this approach.


Protecting people in cities: the disturbing case of Haiti.
Humanitarian actors have sought increasingly not only to assist people affected by natural disasters but also to protect them. This paper examines the efforts of international humanitarian actors to protect Haitians affected by the devastating earthquake of 12 January 2010. It begins with an analysis of the particular difficulties of conceptualising and operationalising protection in an urban environment and traces the efforts of international actors on the ground to develop appropriate protection strategies. The particular difficulties of working with camps and spontaneous settlements in urban areas are explored as are the challenges that stemmed from working with different levels of governmental authorities and a multitude of humanitarian actors. The paper concludes by highlighting some of the lessons learned from the successes and failures of international protection efforts in Haiti. It is hoped that these may assist future efforts to protect people living in urban environments.


Salivary cortisol levels in children during dental treatment.
Cortisol which is also called as stress hormone, is used as an indicator in the stress evaluation studies. 60 children who never visited a dentist before, participated in the present study. Saliva samples were collected from 30 children without any dental treatment (control group). Experimental group comprised 30 children with caries. Saliva samples were obtained at various stages during dental treatment. Totally 180 samples were collected and the cortisol levels were measured. Paired-t test has shown that the salivary cortisol levels at various stages of dental treatment in the experiment group were significantly higher in comparison with the control group. It is concluded that dental treatment may cause extreme stress in children who never had dental treatment experience before.


Infecting dose and severity of malaria: a literature review of induced malaria.
The influence of infecting dose on severity of malaria is unknown. The medical literature contains descriptions and analyses of thousands of people, volunteers and neurosyphilis patients, in whom malaria was induced artificially. In some studies it is possible to relate measures of dose to outcome. In this paper a systematic review of this literature is presented. Dose was inversely related to prepatent and incubation period, as expected. A few studies suggested a relation between dose and severity of disease but others did not. Difficulties in interpreting the studies are emphasized, and the findings are compared with those in experimental animals.


Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model.
Neurosurgical procedures result in surgically induced brain injury (SBI) that causes postoperative complications including brain edema and neuronal apoptosis in the surrounding brain tissue. SBI leads to the release of cytokines that indirectly cause the stimulation of kynurenine 3-monooxygenase (KMO) and the release of neurotoxic quinolinic acid (QUIN). This study tested a KMO inhibitor, RO 61-8048, to prevent postoperative brain edema and consequent neuronal apoptosis in an in vivo model of SBI. A rodent model of SBI was utilized which involves partial resection of the right frontal lobe. A total of 127 Sprague-Dawley male rats (weight 275-325 g) were randomly divided into the following groups: Sham surgical group, SBI, SBI + DMSO, SBI + RO 61-8048 (10 mg/kg), SBI + RO 61-8048 (40 mg/kg), and SBI + RO 61-8048 (40 mg/kg) + KAT II inhibitor PF-04859989 (5 mg/kg). RO 61-8048 was administered by intraperitoneal injection after SBI. Postoperative assessment at different time points included brain water content (brain edema), neurological scoring, and western blot. SBI increased brain water content (ipsilateral frontal lobe), decreased neurological function, and increased apoptotic markers compared with sham animals. Treatment with RO 61-8048 (40 mg/kg) reduced brain water content and improved long-term neurological function after SBI. RO 61-8048 increased the expression of kynurenic acid while reducing QUIN and apoptotic markers in the surrounding brain tissue after SBI. These neuroprotective effects were reversed by PF-04859989. This study suggests KMO inhibition via RO 61-8048 as a potential postoperative therapy following neurosurgical procedures.


Origin of high ammonium, arsenic and boron concentrations in the proximity of a mine: Natural vs. anthropogenic processes.
High ammonium (NH4), arsenic (As) and boron (B) concentrations are found in aquifers worldwide and are often related to human activities. However, natural processes can also lead to groundwater quality problems. High NH4, As and B concentrations have been identified in the confined, deep portion of the Niebla-Posadas aquifer, which is near the Cobre Las Cruces (CLC) mining complex. The mine has implemented a Drainage and Reinjection System comprising two rings of wells around the open pit mine, were the internal ring drains and the external ring is used for water reinjection into the aquifer. Differentiating geogenic and anthropogenic sources and processes is therefore crucial to ensuring good management of groundwater in this sensitive area where groundwater is extensively used for agriculture, industry, mining and human supply. No NH4, As and B are found in the recharge area, but their concentrations increase with depth, salinity and residence time of water in the aquifer. The increased salinity down-flow is interpreted as the result of natural mixing between infiltrated meteoric water and the remains of connate waters (up to 8%) trapped within the pores. Ammonium and boron are interpreted as the result of marine solid organic matter degradation by the sulfate dissolved in the recharge water. The light δ(15)NNH4 values confirm that its origin is linked to marine organic matter. High arsenic concentrations in groundwater are interpreted as being derived from reductive dissolution of As-bearing goethite by dissolved organic matter. The lack of correlation between dissolved Fe and As is explained by the massive precipitation of siderite, which is abundantly found in the mineralization. Therefore, the presence of high arsenic, ammonium and boron concentrations is attributed to natural processes. Ammonium, arsenic, boron and salinity define three zones of groundwater quality: the first zone is close to the recharge area and contains water of sufficient quality for human drinking; the second zone is downflow and contains groundwater suitable for continuous irrigation but not drinkable due to high ammonium concentrations; and the third zone contains groundwater of elevated salinity (up to 5940 μS cm(-1)) and is not useable due to high ammonium, arsenic and boron concentrations.


Effects of stomatal density and leaf water content on the ¹⁸O enrichment of leaf water.
Leaf water isotopic composition is imprinted in several biomarkers of interest and it is imperative that we understand the isotopic enrichment of leaf water. Here, we test the effect of stomatal density and leaf water content on the oxygen isotopic composition of leaf water in transgenic Arabidopsis plants expressing different stomatal densities, and several other species showing a range of stomatal density. We grew Arabidopsis plants hydroponically and collected other species in the field. Stomatal density and leaf water content were determined for each plant. We measured transpiration and extracted leaf water for isotopic determination. Using these measurements and the current leaf water isotope model, we calculated several of the parameters related to leaf water isotopic enrichment. High stomatal density promoted leaf water isotope enrichment. No conclusion, however, can be drawn regarding the effect of leaf water content on leaf water isotope enrichment. Factors such as transpiration might mask the effect of stomatal density on leaf water isotopic enrichment. We propose a method by which stomatal density can be incorporated in the current Peclet model of leaf water isotope enrichment. These findings have important applications in the use of plant-based metabolic proxies in paleoclimate studies.


Determination of phase equilibria in confined systems by open pore cell Monte Carlo method.
We present a modification of the molecular dynamics simulation method with a unit pore cell with imaginary gas phase [M. Miyahara, T. Yoshioka, and M. Okazaki, J. Chem. Phys. 106, 8124 (1997)] designed for determination of phase equilibria in nanopores. This new method is based on a Monte Carlo technique and it combines the pore cell, opened to the imaginary gas phase (open pore cell), with a gas cell to measure the equilibrium chemical potential of the confined system. The most striking feature of our new method is that the confined system is steadily led to a thermodynamically stable state by forming concave menisci in the open pore cell. This feature of the open pore cell makes it possible to obtain the equilibrium chemical potential with only a single simulation run, unlike existing simulation methods, which need a number of additional runs. We apply the method to evaluate the equilibrium chemical potentials of confined nitrogen in carbon slit pores and silica cylindrical pores at 77 K, and show that the results are in good agreement with those obtained by two conventional thermodynamic integration methods. Moreover, we also show that the proposed method can be particularly useful for determining vapor-liquid and vapor-solid coexistence curves and the triple point of the confined system.


Behavioral and adjustment correlates of problem solving: validational analyses of interpersonal cognitive problem-solving measures.
The interpersonal cognitive problem-solving (ICPS) skills (i.e., means-ends thinking, identified obstacles, alternative solutions, consequential thinking) of 150 families (father, mother, and child 6-11 years old) were assessed via written tests and problem-solving behavioral performance. The interrelationships of ICPS written and behavioral problem-solving skills were examined, as were the relationships of each of these measures of problem solving to both parent and teacher indices of child adjustment. IQ, as measured by the age-appropriate Wechsler scale, was partialed out. Results indicated some ecological validity of written alternatives and consequential tests for children and means-ends tests for parents. Neither parents' nor children's written ICPS scores nor problem-solving behavior were systematically related to either teacher or parent ratings of child adjustment. However, a behavioral index of parental facilitation of child problem solving was significantly related to all problem-solving behaviors and some written ICPS measures. Results are discussed in terms of the role of ICPS skills in child adjustment, the potential limits of ICPS measures in therapy outcome, and the manner in which children learn interpersonal cognitive problem solving.


Logistical barriers to career development in academic cardiovascular multimodality imaging-challenges for future mentors.
To define the practical logistics involved in the training, maintenance of technical proficiency, credentialing, and board certification for academic multimodality cardiovascular imaging specialists. Trends in cardiovascular imaging reflect a new paradigm emphasizing expertise in all four major modalities. In order to become a faculty member responsible for educating fellows-in-training, academic imagers face a daunting process with a shortage of senior mentors. Detailed information describing fellowship training, the aggregate monthly volume of publications, credentialing, continuing medical education requirements, and board certification were obtained for each subspecialty area of cardiovascular medicine from various online sources. Compared with other subspecialty areas of cardiovascular medicine, multimodality imaging requires more reading (44% more pages of publications), more continuing medical education hours (300-467% more), and additional board certification (three boards instead of one or two). Achieving competency in multimodality imaging is difficult and expensive in 2009, but still possible. To advance the career development of current academic faculty in this area, future emphasis should be on streamlining training, accreditation, and board certification requirements while focusing on research proving the value of integrated imaging in cardiovascular disease.


[Comparative Analysis of the Efficacy and Safety of Rosuvastatin and Original Rosuvastatin].
The study is one of the priority points of the Russian Scientific Medical Society of Internal Medicine, initiated due to known high average level of LDL cholesterol in Russian population and necessity for its optimized control by better access to treatment. To conduct comparative analysis of efficacy and safety of the rosuvastatin compound akorta and original rosuvastatin crestor. To randomized crossover study (PARITET) 60 patients were included with the diagnosis dyslipidemia. Total duration of treatment phase was 14 weeks - two times by 7 weeks, when the drugs were crossed, separated by 4 weeks washout. Main endpoints were the rate of low density lipoprotein cholesterol (LDL-C) decrease comparing to baseline, and reach of LDL-C guidelines-based target level. After the first 7-week treatment the rate of decrease in akorta group was 49.0+/-15.6%, in crestor 52.6+/-17.4% (p=0.606). After the second period, in respective groups prescription of crestor led to LDL-C decrease by 43.4+/-17.9%, akorta - by 47.2+/-16.3% (p=0.724). After the first period of treatment the value of target levels reach did not differ significantly (akorta - 70.0%, crestor - 83.3%; p>0.05). After the second period in the group crestor-akorta the value was significantly better than in akorta-crestor group (60.0% and 83.3%; p<0.05). Secondary efficacy endpoints were comparable in both groups. Safety parameters were comparable in both groups. The study has shown equivalence of the original rosuvastatin compound crestor and generic compound acorta within the aim of dyslipidemia correction.


Engaging emergency clinicians in emergency department clinical research.
The objective of this panel was to generate recommendations to promote the engagement of front-line emergency department (ED) clinicians in clinical and implementation research. Panel members conducted semi-structured interviews with 37 Canadian adult and pediatric emergency medicine researchers to elicit barriers and facilitators to clinician engagement in research activities, and to glean strategies for promoting clinician engagement. Responses were organized by themes, and, based on these responses, recommendations were developed and refined in an iterative fashion by panel members. We offer eight recommendations to promote front-line clinician engagement in clinical research activities. Recommendations to promote clinician engagement specifically address the creation of a research-friendly culture in the ED, minimizing the burden of data collection on clinical staff through the careful design of data collection tools and the use of research staff, and communication between researchers and clinical staff to promote adherence to study protocols.


High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia.
Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.


A phase I evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early human immunodeficiency virus infection. Military Medical Consortium for Applied Retroviral Research.
Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens. We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored. In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell proliferative responses to gp160. Response was associated with the CD4 cell count determined before vaccination (13 of 16 subjects [81 percent] with greater than 600 cells per milliliter responded, as compared with 6 of 14 [43 percent] with less than or equal to 600 cells per milliliter; P = 0.07) and with the number of injections administered (87 percent of subjects randomly assigned to receive six injections responded, as compared with 40 percent of those assigned to three injections; P = 0.02). Local reactions at the site of injection were mild. There were no adverse systemic reactions, including diminution of general in vitro or in vivo cellular immune function. After 10 months of follow-up, the mean CD4 count had not decreased in the 19 subjects who responded, but it had decreased by 7.3 percent in the 11 who did not respond. This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.


Two cases of adrenal hemangioma: CT and MRI findings with pathological correlations.
We present two cases of adrenal hemangioma, a rare non-functioning adrenal tumor, and correlate the CT and MR imaging findings with the pathological findings. Peripheral spotty contrast enhancement with centripetal enhancement was noted in one case. This pattern of enhancement is crucial for diagnosing adrenal hemangioma. The other case showed only thin rim enhancement without centripetal enhancement. This finding can be seen in other adrenal tumors, making diagnosis difficult. Marked hyperintensity on T2-weighted images and focal hyperintensity on T1-weighted images that showed focal hemorrhage and calcification were noted. These findings can also be seen in other adrenal tumors and are not pathognomonic of adrenal hemangioma. However, observing the combination of these findings can lead to the correct diagnosis.


Bioinformatic Dissecting of TP53 Regulation Pathway Underlying Butyrate-induced Histone Modification in Epigenetic Regulation.
Butyrate affects cell proliferation, differentiation, and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell-cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by ingenuity pathways analysis (IPA) in our RNA-sequencing data set. TP53 signaling pathway plays key role in many cellular processes. TP53 pathway and their involvement in cellular functions modified by butyrate treatment were scrutinized in this report by data mining the RNA-sequencing data using IPA (Ingenuity System(®)). The TP53 mechanistic pathway targets more than 600 genes. Downstream analysis predicted the activation of the TP53 pathway after butyrate treatment. The data mining also revealed that nine transcription factors are downstream regulators in TP53 signaling pathways. The analysis results also indicated that butyrate not only inhibits the HDAC activities, but also regulates genes encoding the HDAC enzymes through modification of histones and epigenomic landscape.


Effect of successive alkylation of N,N-dialkyl amides on the complexation behavior of uranium and thorium: solvent extraction, small angle neutron scattering, and computational studies.
The effect of successive alkylation of the Cα atom adjacent to the carbonyl group in N,N-dialkyl amides (i.e., di(2-ethylhexyl)acetamide (D2EHAA), di(2-ethylhexyl)propionamide (D2EHPRA), di(2-ethylhexyl)isobutyramide (D2EHIBA), and di(2-ethylhexyl)pivalamide (D2EHPVA)) on the extraction behavior of hexavalent uranium (U(VI)) and tetravalent thorium (Th(IV)) ions has been investigated. These studies show that the extraction of Th(IV) is significantly suppressed compared to that of U(VI) with increased branching at the Cα atom adjacent to the carbonyl group. Small angle neutron scattering (SANS) studies showed an increased aggregation tendency in the presence of nitric acid and metal ions. D2EHAA showed more aggregation compared to its branched homologues, which explains its capacity for higher extraction of metal ions. These experimental observations were further supported by density function theory calculations, which provided structural evidence of differential binding affinities of these extractants for uranyl cations. The complexation process is primarily controlled by steric and electronic effects. Quantum chemical calculations showed that local hardness and polarizability can be extremely useful inputs for designing novel extractants relevant to a nuclear fuel cycle.


Current trends in diagnostic biomarkers of acute coronary syndrome.
The diagnosis and management of patients with acute coronary syndrome (ACS) have evolved dramatically over the past decade. Biomarkers play an important role in the diagnosis of ACS, especially in unstable angina and non-ST-segment elevation myocardial infarction. Among these, cardiac troponin and creatine kinase appear to be the most sensitive and specific markers of myocardial injury. Recent studies have revealed several novel biomarkers. Elevated levels of C-reactive protein and interleukin-6 are strong independent markers of increased mortality among patients with ACS. However, the ideal biomarkers that offer early detection, risk stratification, selection of therapy, monitoring disease progression, and treatment efficacy remain to be elucidated. This review assesses limitations and contemporary needs for biomarkers in the context of diagnosis of ACS. It also discusses the newly developing technologies for novel biomarkers or novel biomarker protein signatures discovery, and importance of point-of-care testing for future management.


The genome sequence of the tree of heaven, Ailanthus altissima (Mill.) Swingle, 1916.
We present a genome assembly from an individual Ailanthus altissima (tree of heaven; Streptophyta; Magnoliopsida; Sapindales; Simaroubaceae). The genome sequence is 939 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies are 661.1 kilobases and 161.1 kilobases long, respectively.


Impact of a combination of a calcium antagonist and a beta-blocker on cell- and copper-mediated oxidation of LDL and on the accumulation and efflux of cholesterol in human macrophages and murine J774 cells.
Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. In the absence of data pertaining to the potential cardioprotective action of an association of such agents, we have investigated the impact of nifedipine and atenolol, alone or in combination, on the capacity of monocyte-macrophages (ex vivo) and copper ions (in vitro) to oxidize LDL and on intracellular metabolism and efflux of free and esterified forms of cholesterol in human macrophages and foam cells. At concentrations up to 100 micromol/L, atenolol had no effect on the oxidative resistance of LDL; on the contrary, nifedipine displayed a significant dose-dependent capacity to protect LDL during copper-mediated oxidation (100 micromol/L; P<.001). Using a DPPH radical generating system, nifedipine was shown to exert free radical-trapping activity (molar ratio of scavenging activity, nifedipine:alpha-tocopherol, 1:114). The addition of atenolol to nifedipine was without effect on the antioxidant activity of the calcium antagonist. In experiments in which oxidative modification was mediated by monocyte-macrophages, nifedipine but not atenolol conserved its antioxidant capacity. Furthermore, we demonstrated that association of atenolol with nifedipine did not modify the antioxidant properties of nifedipine itself. Using a human monocyte-derived macrophage culture system, nifedipine, atenolol, or a combination of the two drugs was ineffective in inhibiting foam cell formation induced by acetylated LDL or oxidized LDL. However, atenolol (100 micromol/L) increased cellular accumulation of cholesteryl ester (+17%; P<.05), whereas nifedipine (100 micromol/L) decreased total cholesterol (-37.4%; P<.05) accumulation induced by acetylated LDL in the mouse macrophage cell line J774. A combination of the two drugs neutralized these antagonistic effects. None of these results were reproduced during the oxidized LDL-induced transformation of murine J774 cells into foam cells. Furthermore, cholesterol efflux from preloaded human macrophages was equally unaffected by the addition of the drugs alone or in combination. It therefore seems unlikely that the beneficial effect of atenolol on coronary heart disease is mediated by changes in either LDL oxidizability or cholesterol metabolism in human macrophages and foam cells. Our findings with nifedipine suggest, however, that this calcium antagonist may potentially exert antiatherosclerotic properties via a reduction of the oxidative modification of LDL, thereby affecting a reduction in foam cell formation and in the pathophysiological cellular activities of oxidized lipids, rather than by inducing a direct reduction in cholesterol accumulation in human foam cells of macrophage origin.


Evidence for electroactive excitation of the spin cycloid in TbMnO3.
Terahertz electromagnetic excitations in the multiferroic TbMnO3 single crystals are investigated across the magnetic field induced rotation of the magnetic spin cycloid. In addition to the electromagnon along the a axis, the detailed polarization analysis of the experimental spectra suggests the existence of an electroactive excitation for ac electric fields of the electromagnetic wave along the crystallographic c axis. This excitation is possibly the electroactive eigenmode of the spin-cycloid in TbMnO3, which has been predicted within the inverse Dzyaloshinskii-Moriya mechanism of magnetoelectric coupling.


Thyroid-Like Follicular Carcinoma of the Kidney.
Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare but emerging renal neoplasm that morphologically mimics follicular carcinoma of the thyroid but lacks immunohistochemical expression of thyroid markers such as TTF-1 and thyroglobulin. Here, a case of an incidentally discovered TLFCK in a 27-year-old man is reported. Histologic evaluation demonstrated an encapsulated proliferation of variably sized thyroid follicle-like epithelial-lined spaces filled with colloid-like eosinophilic secretions. Immunohistochemical analysis confirmed lack of expression of the thyroid markers TTF-1 and thyroglobulin with expression of PAX8 and CD10, confirming a neoplasm of renal origin, which correlated to the clinical and radiographic absence of thyroid pathology. In this report, this case is described with an emphasis on the differential diagnosis.


Rapid identification of pyoverdines of fluorescent Pseudomonas spp. by UHPLC-IM-MS.
Siderophores are iron-chelating molecules produced by bacteria and other microbes. They are involved with virulence in infections and play key roles in bacterial community assembly and as plant protectants due to their pathogen control properties. Although assays exist to screen whether newly isolated bacteria can produce siderophores, the chemical structures of many of these bio-active molecules remain unidentified due to the lack of rapid analytical procedures. An important group of siderophores are pyoverdines. They consist of a structurally diverse group of chromopeptides, whose amino acid sequence is characteristic for the fluorescent Pseudomonas species that secrets them. Although over 60 pyoverdine structures have been described so far, their characterization is cumbersome and several methods (isoelectrofocusing, iron uptake measurement, mass determination) are typically combined as ambiguous results are often achieved by a single method. Those additional experiments consume valuable time and resources and prevent high-throughput analysis. In this work, we present a new pyoverdine characterisation option by recording their collision cross sections (CCS) using trapped ion mobility spectrometry. This can be done simultaneously in combination with UHPLC and high-resolution MS resulting in a rapid identification of pyoverdines. The high specificity of CCS values is presented for 17 pyoverdines secreted by different Pseudomonas strains. The pyoverdine mass determination by full scan MS was supported by fragments obtained from broadband collision induced dissociation (bbCID). As iron contaminations in laboratories are not uncommon, CCS values of ferripyoverdines were also evaluated. Thereby, unusual and highly characteristic ion mobility patterns were obtained that are suitable as an alternative identification marker.


Distributed Signal Decorrelation and Detection in Multi View Camera Networks Using the Vector Sparse Matrix Transform.
This paper introduces the vector sparse matrix transform (vector SMT), a new decorrelating transform suitable for performing distributed processing of high-dimensional signals in sensor networks. We assume that each sensor in the network encodes its measurements into vector outputs instead of scalar ones. The proposed transform decorrelates a sequence of pairs of vector outputs, until these vectors are decorrelated. In our experiments, we simulate distributed anomaly detection by a network of cameras, monitoring a spatial region. Each camera records an image of the monitored environment from its particular viewpoint and outputs a vector encoding the image. Our results, with both artificial and real data, show that the proposed vector SMT transform effectively decorrelates image measurements from the multiple cameras in the network while maintaining low overall communication energy consumption. Since it enables joint processing of the multiple vector outputs, our method provides significant improvements to anomaly detection accuracy when compared with the baseline case when the images are processed independently.


Rapid quantification of lymphocyte subsets in heterogeneous cell populations by flow cytometry.
Determination of the number of viable cells or quantification of lymphocyte subsets in heterogeneous cell populations is critically important for cytotoxicity assays, apoptosis assays, or the analysis of differential activation of T-cell subsets by distinct stimuli. In this report, we describe a rapid flow cytometry method termed Standard Cell Dilution Analysis (SCDA) specifically to quantify any subset of phenotypically definable, viable cells in heterogeneous populations using a FACScan flow cytometer. This method combines: (1) specific detection of lymphocyte subsets by phycoerythrin-conjugated monoclonal antibodies, (2) electronic exclusion of dead cells or cell debris by propidium-iodide staining and gating on forward vs. sidescatter, respectively, and (3) admixture of a known amount of fixed, fluorescein isothiocyanate stained cells immediately before analysis as a constant parameter to allow for calculation of cell quantity. We have used SCDA to analyze the in vitro growth characteristics of various human T-lymphocyte subpopulations in response to different activation stimuli.


Ultrasonographic assessment of skeletal muscle mass and diaphragm function in patients with chronic obstructive pulmonary disease: A case-control study.
Although muscle dysfunction is a major contributor to morbidity in chronic obstructive pulmonary disease (COPD), assessment of skeletal muscle, and diaphragm function is not routinely performed in COPD patients. (1) The aim is to assess muscle dysfunction in COPD by measuring the zone of apposition of diaphragm, diaphragm excursion, thickness of diaphragm, and rectus femoris cross-sectional area (RFCSA) with ultrasonography.(2) To correlate the above assessments with spirometric parameters; notably forced expiratory volume in 1 s (FEV1). Twenty-four consecutive stable COPD patients and 18 controls were included after obtaining written informed consent. Demographic and clinical data, spirometric values, 6-min walk distance, and sonographic parameters mentioned above were compiled for the analysis. All included participants were male with a mean age of 62.5 ± 8.4 years. The mean FEV1in cases was 1.12 ± 0.4 L versus 2.41 ± 0.5 L in controls. The diaphragm thickness (1.8 ± 0.5 mm vs. 2.2 ± 0.6 mm;P = 0.005) and RFCSA was significantly lower in COPD patients (4.8 ± 1.3 cm[2] vs. 6.12 ± 1.2 cm[2];P = 0.02). However, diaphragm excursion (5.35 ± 2.8 cm vs. 7 ± 2.6 cm) although lower in COPD patients, was not significantly different between the groups. Correlation between FEV1and ultrasound diaphragm measurements and RFCSA by Spearman's Rho correlation was poor (ρ= 0.2). Ultrasonographic assessment of the diaphragm and rectus femoris can be used as markers to assess skeletal muscle dysfunction in COPD as diaphragmatic function and RFCSA were lower in COPD patients.


Tunneling technique of PICCs and Midline catheters.
The tunneling technique is currently widely used for placement of CVC. Recently, some clinicians have used this technique for peripherally inserted central catheters (PICC), or Midline catheters (MCs). To describe a safe antegrade tunneling technique for PICCs and MCs insertion with a blunt tunneler. This retrospective monocentric survey collected ASST Lodi hospital data from January 1st to December 31st, 2019. The indication for PICCs and MCs tunneled implant was to respect the correct vein/catheter ratio or special clinical situation (children, burns, wounds, and wider catheter 5/6 fr). Contraindications included the operator's low skills and severe risk of bleeding (INR > 3; Platelet count <50'000). About 390 PICCs (327 4 fr and 63 5 fr) and 183 MCs were placed. One hundred and sixty-five PICCs (42%) and 110 MCs (60%) were tunneled. Five fr PICCs were more present among tunneled catheters (54/165 [32.7%] vs 9/225 [4%] p < 0.0001). In the majority tunneling was necessary to respect the correct catheter/vein ratio. The exit site was shifted only for four special clinical situations: skin infections (one PICC and two MCs); burns (one MC). No early complication (intraprocedural, major bleeding), catheter related thrombosis, or device fractures occurred. Two catheter-related bloodstream infections (one PICC, one MC), nine dislocations (four PICCs, five MCs), one MC occlusion were recorded. The antegrade tunneling technique with blunt tunneler of PICCs and MCs is simple, rapid and is regarded as a safe maneuver. More in-depth and future prospective studies are needed to evaluate the impact of tunneling on early and late complications.


Clinical trials of natural products as chemopreventive agents for prostate cancer.
Epidemiological research on prostate cancer risk in men throughout the world has identified significant correlations between dietary habits and prostate cancer occurrence. These studies served as a catalyst for exploration into the potential of dietary substances to act as chemopreventive agents against this disease, and include green tea catechins, lycopene, soy isoflavones, pomegranate phenolics, selenium, vitamins E and D, curcumin and resveratrol. Before these agents (in the dietary or purified forms) can be recommended as useful chemopreventive strategies for patients, their activity must be confirmed in rigorously designed clinical trials. This review discusses the preclinical and clinical data available for these dietary agents and describes relevant clinical trials currently being conducted.


Enantioselective [3 + 2] Annulation of Enals with 2-Aminoacrylates Catalyzed by N-Heterocyclic Carbene.
A novel and convenient strategy for the enantioselective synthesis of γ-lactam derivatives via N-heterocyclic carbene catalyzed formal [3 + 2] annulation of enals with 2-aminoacrylates is disclosed. This activation mode provides a complementary approach to the synthesis of various γ-lactam derivatives in good yields with excellent diastereo- and enantioselectivities. In this process, two consecutive stereocenters are constructed, and a quaternary carbon center is also established.


Fate of the dissected aortic arch after ascending replacement in type A aortic dissection†.
To evaluate the fate of a dissected aortic arch after limited surgical repair of type A aortic dissection. Of the 271 patients operated for acute type A dissection between 2001 and 2015, 86 (age 57 ± 13 years, 74% men) with predischarge computed tomographic (CT) scans had a residual dissection in the arch. Aortic diameters, lengths, ellipticity and communications between lumina were assessed using predischarge and follow-up CT scans. The median CT scan follow-up was 31 months (first quartile 15, third quartile 52). The largest increase in the total aortic diameter at follow-up was 20 mm distal to the left subclavian artery (median +4.0 mm; first quartile +1.5, third quartile +9.2 mm; P = 0.004), with an average growth rate of 1.5 mm/year (first quartile 0.6, third quartile 3.9 mm). The true lumen diameter was unchanged at follow-up. At least 1 communication between the true and the false lumina was observed in 80% of patients on the predischarge CT scan, and 70% had communications at the distal aorta-graft anastomosis. Accelerated increase in the diameter of the dissected aorta was associated with the number of communications between the lumina, communication at the distal anastomosis and false lumen perfusion (all, P < 0.001). Dissection of the residual aortic arch leads to aortic growth that may result in an aneurysm requiring treatment. The number of communications between the lumina, communication at the distal anastomosis and false lumen perfusion are associated with the accelerated aortic growth. Endovascular repair may be difficult due to the small true lumen and the presence of many communications between the lumina.


Fetal activity acceleration determination for the evaluation of fetal reserve.
Fetal activity acceleration determination (FAD) was performed 462 times on a total of 410 patients for the evaluation of fetal reserve. Simultaneous oxytocin challenge test (OCT) was performed 324 times to evaluate the correlation between the two tests. In 308 instances, FAD was positive and OCT was either negative or probably negative. In 2 cases with inadequate FAD results the simultaneous OCT was suspicious and positive. In four instances of negative FAD the simultaneous OCT was positive. The correlation between the two tests was excellent. The outcome of all cases with positive FAD was also excellent. The result of the present study strongly suggests that the positive FAD indeed provides reassurance of fetal well-being. Only the inadequate or negative FAD requires the performance of an OCT for further evaluation of the fetal condition.


Genetic and expression variations of cell cycle pathway genes in brain tumor patients.
The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = -0.291*, P<0.05) in brain tumors. Expression levels of selected genes were also assessed at protein level using immunohistochemical analysis (IHC) and signification down-regulation of RB1 (P=0.0001) and up-regulation of CCND1 (P=0.0001) was observed in brain tumor compared with control sections. In conclusion, it is suggested that polymorphisms/expression variations of RB1 and CCND1 genes may be associated with increased risk of brain tumor.


Association Between Medicare Star Ratings for Patient Experience and Medicare Spending per Beneficiary for US Hospitals.
To test the association between patient experience and Centers for Medicare and Medicaid Services (CMS) spending at the hospital level. Using CMS Hospital Compare data set, we analyzed 2014 data for CMS patient experience star ratings and the hospital Medicare Spending per Beneficiary (MSPB) Measure, which assesses price-standardized, risk-adjusted payments for services provided to Medicare beneficiaries for an episode of care from 3 days before hospital admission to 30 days following discharge. We tested the association using linear regression, adjusting for complexity of care using hospital Case Mix Index (CMI) and for socioeconomic status of the hospital patient population using Disproportionate Share Hospital (DSH) status. The MSPB decreased with increasing hospital patient experience ratings. After adjustment for CMI and DSH, better hospital patient experience was associated with lower spending per episode (5.6% decrease from the lowest to highest patient experience star rating). We found that better hospital patient experience was associated with lower health-care spending. Further research is needed to define what specific elements and phases of the episode of care are driving the association.


Comparative study of two immunocytochemical techniques in the electron microscopical detection of alpha-1-antitrypsin in routinely processed liver biopsies.
Two indirect immunocytochemical techniques using different markers, namely peroxidase and gold, were applied to ultrathin sections of liver biopsies to detect alpha-1-antitrypsin. The blocks used were taken from the routine electron microscopy files and had been processed optimally for maximum ultrastructural preservation. The immunogold technique provided the best method for localizing alpha-1-antitrypsin and was associated with ultrastructural preservation equivalent to that seen in routinely processed liver biopsies. The procedure may be a useful adjunct to understanding the pathogenesis of alpha-1-antitrypsin deficiency and in recognizing further variants of this disorder.


Foundations for a human science of nursing: Gadamer, Laing, and the hermeneutics of caring.
The professions of nursing and nurse education are currently experiencing a crisis of confidence, particularly in the UK, where the Francis Report and other recent reviews have highlighted a number of cases of nurses who no longer appear willing or able to 'care'. The popular press, along with some elements of the nursing profession, has placed the blame for these failures firmly on the academy and particularly on the relatively recent move to all-graduate status in England for pre-registration student nurses. This has come to be known in the UK as the 'too-posh-to-wash' argument, that there is an incommensurability between being educated to degree level and performing basic nursing tasks. I will argue in this paper that the diagnosis of the problem is substantively correct, but the formulation and the prescription are misguided and dangerous. I will suggest that the growing emphasis on research-based and evidence-based practice is the logical conclusion of an inappropriate scientific paradigm for nursing which is underpinned by the social sciences, by technical rationality, and by a focus on people. In contrast, I will suggest that a more fruitful way of thinking about and practising nursing and nurse education is to consider it as a human science with a focus on persons in which evidence for practice derives largely from practice itself. The history of the idea of a human science is traced from its roots in nineteenth century hermeneutics to the work of Gadamer and R.D. Laing in the 1960s, and I attempt to imagine a paradigm for nursing practice, scholarship, and education based on Laing's 'existential-phenomenological' approach with a focus on the endeavour to understand and relate to individual persons rather than to make broad prescriptions for practice based on statistical and other generalizations.


[A case of coccidioidomycosis in Plzen].
A case of the pulmonary form of coccidioidomycosis of a Czech patient infected in Arizona is described. The disease was diagnosed on the basis of serological tests. In addition to a review of the mycological, epidemiological and clinical picture of coccidioidomycosis criteria of laboratory mycological diagnostics are given. It is important to be aware of this mycosis in patients who have a history of recent visits to endemic areas in North, Central and South America.


Towards a Machine-Learning Approach for Sickness Prediction in 360° Stereoscopic Videos.
Virtual reality systems are widely believed to be the next major computing platform. There are, however, some barriers to adoption that must be addressed, such as that of motion sickness - which can lead to undesirable symptoms including postural instability, headaches, and nausea. Motion sickness in virtual reality occurs as a result of moving visual stimuli that cause users to perceive self-motion while they remain stationary in the real world. There are several contributing factors to both this perception of motion and the subsequent onset of sickness, including field of view, motion velocity, and stimulus depth. We verify first that differences in vection due to relative stimulus depth remain correlated with sickness. Then, we build a dataset of stereoscopic 3D videos and their corresponding sickness ratings in order to quantify their nauseogenicity, which we make available for future use. Using this dataset, we train a machine learning algorithm on hand-crafted features (quantifying speed, direction, and depth as functions of time) from each video, learning the contributions of these various features to the sickness ratings. Our predictor generally outperforms a naïve estimate, but is ultimately limited by the size of the dataset. However, our result is promising and opens the door to future work with more extensive datasets. This and further advances in this space have the potential to alleviate developer and end user concerns about motion sickness in the increasingly commonplace virtual world.


Health Care Trainees' and Professionals' Perceptions of ChatGPT in Improving Medical Knowledge Training: Rapid Survey Study.
ChatGPT is a powerful pretrained large language model. It has both demonstrated potential and raised concerns related to knowledge translation and knowledge transfer. To apply and improve knowledge transfer in the real world, it is essential to assess the perceptions and acceptance of the users of ChatGPT-assisted training. We aimed to investigate the perceptions of health care trainees and professionals on ChatGPT-assisted training, using biomedical informatics as an example. We used purposeful sampling to include all health care undergraduate trainees and graduate professionals (n=195) from January to May 2023 in the School of Public Health at the National Defense Medical Center in Taiwan. Subjects were asked to watch a 2-minute video introducing 5 scenarios about ChatGPT-assisted training in biomedical informatics and then answer a self-designed online (web- and mobile-based) questionnaire according to the Kirkpatrick model. The survey responses were used to develop 4 constructs: "perceived knowledge acquisition," "perceived training motivation," "perceived training satisfaction," and "perceived training effectiveness." The study used structural equation modeling (SEM) to evaluate and test the structural model and hypotheses. The online questionnaire response rate was 152 of 195 (78%); 88 of 152 participants (58%) were undergraduate trainees and 90 of 152 participants (59%) were women. The ages ranged from 18 to 53 years (mean 23.3, SD 6.0 years). There was no statistical difference in perceptions of training evaluation between men and women. Most participants were enthusiastic about the ChatGPT-assisted training, while the graduate professionals were more enthusiastic than undergraduate trainees. Nevertheless, some concerns were raised about potential cheating on training assessment. The average scores for knowledge acquisition, training motivation, training satisfaction, and training effectiveness were 3.84 (SD 0.80), 3.76 (SD 0.93), 3.75 (SD 0.87), and 3.72 (SD 0.91), respectively (Likert scale 1-5: strongly disagree to strongly agree). Knowledge acquisition had the highest score and training effectiveness the lowest. In the SEM results, training effectiveness was influenced predominantly by knowledge acquisition and partially met the hypotheses in the research framework. Knowledge acquisition had a direct effect on training effectiveness, training satisfaction, and training motivation, with β coefficients of .80, .87, and .97, respectively (all P<.001). Most health care trainees and professionals perceived ChatGPT-assisted training as an aid in knowledge transfer. However, to improve training effectiveness, it should be combined with empirical experts for proper guidance and dual interaction. In a future study, we recommend using a larger sample size for evaluation of internet-connected large language models in medical knowledge transfer.


Antiinflammatory and antipyretic activity of Michelia champaca Linn., (white variety), Ixora brachiata Roxb. and Rhynchosia cana (Willd.) D.C. flower extract.
Methanolic extracts of the flowers of M. champaca, I. Brachiata and R. cana were found to possess antiinflammatory activity against cotton pellet granuloma in rats at a dose level of 100 mg/kg body weight, sc. The latter two drugs showed higher activity (AIA) as compared to that of M. champaca. They reduced the protein content, acid phosphatase, glutamate pyruvate transaminase and glutamate oxalo-acetate transaminase activities in liver and serum. A significant reduction in the ascorbic acid content in adrenals was also observed in drug-treated animals. R. cana was recorded to possess significant antipyretic activity from the first hour of administration. These pharmacological properties may be traced to the presence of flavonoids in the flowers of these plants.


Laparoscopic versus open surgery for rectal cancer: a systematic review and meta-analysis of randomized controlled trials.
Laparoscopic and open rectum surgery for rectal cancer remains controversial. This systematic review compared the short-term and long-term efficiency and complications associated with laparoscopic and open resection for rectal cancer. We searched PubMed, Embase, Cochrane Library, ISI Web of Knowledge and the China Biology Medicine Database to identify potential randomized controlled trials from their inception to March 31, 2014 without language restriction. Additional articles were identified from searching bibliographies of retrieved articles. Two reviewers independently assessed the full-text articles according to the pre-specified inclusion and exclusion criteria as well as the methodological quality of included trials. The meta-analysis was performed using RevMan 5.2. A total of 16 randomized controlled trials involving 3,045 participants (laparoscopic group, 1,804 cases; open group, 1,241 cases) were reviewed. Laparoscopic surgery was associated with significantly lower intraoperative blood loss, earlier return of bowel movement and reduced length of hospital stay as compared to open surgery, although with increased operative time. It also showed an obvious advantage for minimizing late complications of adhesion-related bowel obstruction. Importantly, there were no significant differences in other postoperative complications, oncological clearance, 3-year and 5-year or 10 year recurrence and survival rates between two procedures. On the basis of this meta-analysis we conclude that laparoscopic surgery has advantages of earlier postoperative recovery, less blood loss and lower rates of adhesion-related bowel obstruction. In addition, oncological outcome is comparable after laparoscopic and open resection for rectal cancer.


Tympanometry. ASHA Working Group on Aural Acoustic-Immittance Measurements Committee on Audiologic Evaluation.
Most of the available tympanometric data have been generated with instruments that measure immittance magnitude at 226 Hz. These limited measurements are valuable in evaluating middle-ear pathologies such as effusion and tympanic-membrane perforations but are not always adequate in evaluating pathologies of the ossicular chain such as otosclerosis and ossicular discontinuity. In response to this shortcoming, manufacturers of the newest generation of immittance devices have incorporated variable frequency or click probe signals. With these new instruments, it is possible to evaluate the middle-ear transmission system over its normal range of functioning. These new instruments also are computer based. If two-component, multifrequency immittance measurements are input to the computer, it then becomes possible to analyze and plot the data in many forms. Presently, the technology has outpaced the clinical understanding of these complex measures. The intent of this tutorial was to focus on areas of tympanometry not widely discussed in previous writings. The first two sections on terminology and instrumentation encourage clinicians to know their instruments and to use standardized terminology in communicating data. Much of the remaining information focused on the new generation of multifrequency immittance systems. Examples of normal and pathological tympanograms were plotted at a number of frequencies and in a variety of formats. In the beginning, tympanometric measures will be cumbersome, but as research begins to focus on these new measurements, the best frequency range and frequency interval and the best plotting formats will be identified. In conducting these studies, the procedural (e.g., rate and direction of ear-canal pressure change and the number of successive tympanometric runs) and computational (calculation at peak or 0 daPa and calculation of ear-canal contributions) variables must be specified if the data are to be universally applicable. Once these questions are answered, tympanometric measures with computer-based instruments will be rapid and informative. Enough data do not yet exist to incorporate multiple-frequency tympanometry into screening programs. Future research will need to address the efficacy of more complex tympanometric screening procedures. It is possible that the 226-Hz screening procedure will prove most efficient in school-aged children, the majority of whom whould be identified as having middle-ear effusion by the present procedure, or in the case of ossicular-chain abnormality, would have a significant hearing loss.(ABSTRACT TRUNCATED AT 400 WORDS)


Interpretation of the dose and LET dependence of RBE values for lethal lesions in yeast cells.
Survival data on yeast cells proficient or deficient in the repair of DNA double-strand breaks (dsb) and data on the induction of dsb are used to interpret the dose dependence of the RBE value for lethal lesions after irradiation at high dose rate followed by 72-hr liquid holding providing optimum conditions for repair of potentially lethal lesions (RBEDP, DP = delayed plating). The radiations applied are conventional (150 kV), soft (50 kV), and ultrasoft (4 kV) X rays, 30-MeV electrons (or 60Co gamma rays), and 3.5-MeV alpha particles. Analysis shows that the dose dependence of the RBEDP value can be explained by the combination of two dose-independent RBE values, one for the single-particle traversal effect (RBEspt) and the other for the accumulation of dsb (RBEdsb) due to the traversal of more than one particle through the cell nucleus. Furthermore, it is shown that the LET dependence of RBEspt values describing the linear component of the lethal lesions must be considered separately for "electron" and "particle" radiations.


Secondary cleft rhinoplasty: impact on self-esteem and quality of life.
Rhinoplasty is one of the most challenging facial plastic procedures. Although patient satisfaction is the real outcome parameter in rhinoplasty, most authors have studied objective outcomes evaluated by professionals. The purpose of this study was to determine patient satisfaction after rhinoplasty in patients born with a cleft lip compared with outcome assessment by professionals, and to assess the impact of the procedure on appearance-related distress and generic quality of life. Patient evaluation of the nose was performed before and 1 year after secondary cleft rhinoplasty (n = 33) using a visual analogue scale for nasal function and shape, and the Rhinoplasty Outcome Evaluation. General sinonasal complaints were evaluated using the Sino-Nasal Outcome Test. Appearance-related psychological distress was measured using the Derriford Appearance Scale. The Sheehan Disability Scale evaluated quality of life. Aesthetic outcome was evaluated by scoring of preoperative and postoperative photographs by two independent surgeons. One year postoperatively, patients showed significantly higher visual analogue scale scores for nasal shape (p < 0.0001) and function (p = 0.005) and higher Rhinoplasty Outcome Evaluation (p < 0.0001) scores. Correspondingly, Sino-Nasal Outcome Test scores were lower (p = 0.006). The appearance-related psychological distress was lower (p < 0.0001), and the generic quality of life was increased after rhinoplasty (p = 0.01). No correlation was found between patient outcome evaluation and surgeons' scores. There is high patient satisfaction at 12 months after secondary cleft rhinoplasty, resulting in a significant improvement of self-esteem and generic quality of life.


Clearance receptors for tissue-type plasminogen activator.
Hepatic clearance is one of the principal mechanisms regulating plasma concentrations of tissue-type plasminogen activator (t-PA). Two distinct pathways appear to be involved. Liver endothelial cells and Kupffer cells clear t-PA via the mannose receptor, whereas parenchymal cells clear t-PA via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR). This review presents the structural determinants on the t-PA molecule that mediate clearance via these two pathways, gives an overview of the structure of the LRP/alpha 2-MR and discusses the role of plasminogen activator inhibitor type 1 (PAI-1) in the hepatic clearance of t-PA.


Pulmonary toxicity induced by mitomycin C is highly responsive to glucocorticoids.
The authors have studied five cases of biopsy-proven pulmonary toxicity caused by the administration of mitomycin C (M), vincristine, and cisplatin in 64 patients with advanced non-small cell lung cancer. The clinical triad of progressive dyspnea, rales, and pulmonary infiltrates presented in all five cases. In addition, pulmonary function tests showed hypoxemia (four/five), reduced forced vital capacity (three/four), total lung capacity (two/three), and forced expiratory volume (FEV1) (three/four) and very profound reduction in diffusion capacity (three/three). Transbronchial biopsy for tissue examination was necessary to rule out other causes. Characteristics but nonspecific pathologic changes were documented in all five cases. All the patients responded quickly and dramatically to high-dose glucocorticoids with improvement of hypoxia, dyspnea, exercise tolerance, and sense of well being. In three patients the pulmonary infiltrates cleared. However, abrupt stopping or early withdrawal of steroid resulted in aggravation of dyspnea and pulmonary infiltrate in three cases who improved subsequently with escalation of steroid doses. The authors conclude that the treatment of choice for pulmonary toxicity induced by M or M-containing chemotherapy regimens is a high dose of glucocorticoid and discontinuation of M at once when suspicion is raised.


Spontaneous acute stanford type B thoracic aortic dissection treated successfully with endovascular stent graft.
Aortic dissection is a rare entity with an incidence estimated to be 5-30 cases per million people per year. It is more common in patients with hypertension, connective tissue disorders, congenital aortic stenosis or bicuspid aortic valve, and in those with first-degree relatives with history of thoracic dissections. Spontaneous dissections are rare. We describe one such case who was treated successfully with a endovascular stent graft without any local or systemic complication.


Pauli Spin Blockade of Heavy Holes in a Silicon Double Quantum Dot.
In this work, we study hole transport in a planar silicon metal-oxide-semiconductor based double quantum dot. We demonstrate Pauli spin blockade in the few hole regime and map the spin relaxation induced leakage current as a function of interdot level spacing and magnetic field. With varied interdot tunnel coupling, we can identify different dominant spin relaxation mechanisms. Application of a strong out-of-plane magnetic field causes an avoided singlet-triplet level crossing, from which the heavy hole g-factor ~0.93 and the strength of spin-orbit interaction ~110 μeV can be obtained. The demonstrated strong spin-orbit interaction of heavy holes promises fast local spin manipulation using only electric fields, which is of great interest for quantum information processing.


Video-assisted surgery for thyroid cancer patients.
Today is well known that endoscopic thyroidectomy could reach the same level of completeness as a conventional operation. We have been using minimally invasive video assisted thyroidectomy (MIVAT) as our favorite minimally invasive access to thyroid diseases from the late nineties. Our experience with MIVAT is represented by 2,413 cases between 1998 and 2014: in particular 821 patients were operated with a total thyroidectomy for a papillary carcinoma (34.0%). Furthermore 967 patients underwent a MVAT for the presence of an undetermined lesion (40.0%). The conversion rate was very low: 24 patients (1.0%), mainly due to: unexpected posterior tracheal invasions (nine patients), involvement of lymph nodes not evident at echography (four patients), esophageal infiltration (three patients), strap muscles infiltration (three patients) and finally in five cases the presence of serious thyroiditis that had escaped to ultrasonographic evaluation. The minimally MIVAT to treat malignant thyroid tumors has today a very clear indication for malignancies.


Intradermal inoculations of low doses of Leishmania major and Leishmania amazonensis metacyclic promastigotes induce different immunoparasitic processes and status of protection in BALB/c mice.
In order to simulate the natural long term parasitisms which may occur in mammals infected with Leishmania, cutaneous leishmaniases due to Leishmania major or Leishmania amazonensis were induced using a model based on the inoculation of 10-1000 metacyclic promastigotes into the ear dermis of BALB/c mice. The final outcome of these parasitisms was dependent upon the number of inoculated parasites. Only some of the mice inoculated with ten parasites displayed cutaneous lesions, whereas most mice infected with 100 metacyclics and all mice infected with 1000 metacyclics developed progressive lesions. We found, using the latter experimental conditions, that the onset of the pathology was associated with: (a) parasite multiplication in the inoculation site and the draining lymph node correlating with an increase of the lymph node cell number, especially in L. major-infected mice; and (b) the detection of lymph node cells, at least in part CD4(+) T lymphocytes, able to produce high levels of interferon-gamma, interleukin (IL)-4, IL-10 and IL-13. Thereafter, mice infected by L. major harboured few parasites in the ear and had a 100-fold reduction in lymph node parasite load between 23 and 40 weeks post-inoculation. In contrast, the parasite loads of L. amazonensis-infected mice remained stable in the ear and increased in nodes during the same period of time. Only L. major-infected mice that exhibited cutaneous lesions in the primary site were resistant to the re-inoculation of 1000 metacyclic promastigotes, whereas all L. amazonensis-primary infected mice remained susceptible to a second homologous challenge. These results are the first to document that a status of resistance to re-infection, referred to concomitant immunity, is coupled to the development of primary progressive lesions in L. major-infected BALB/c mice. Such a protective status is absent in L. amazonensis-infected BALB/c mice.


Hydrogen production by the thermophilic bacterium Thermotoga neapolitana.
Virtually all members of the order Thermotogales have demonstrated the ability to produce hydrogen; however, some members of this order produce considerably greater quantities than others. With one representative of this order, Thermotoga neapolitana, we have consistently obtained accumulation of 25-30% hydrogen with 12-15% carbon dioxide as the only other prominent product in the batch reaction. In contradistinction to information widely disseminated in the literature, we have also found that most members of this order tolerate and appear to utilize the moderate amounts of oxygen present in the gaseous phase of batch reactors (6-12%), with no apparent decrease in hydrogen production. Hydrogen accumulation has been widely reported to inhibit growth of Thermotogales. While this may be true at very high hydrogen tensions, we have observed log phase bacterial morphology (rods) even in the presence of 25-35% hydrogen concentrations. To maximize hydrogen production and minimize production of hydrogen sulfide, inorganic sulfur donors are avoided and the cysteine concentration in the medium is increased. We and others have demonstrated that different members of the order Thermotogales utilize a wide variety of feedstocks, including complex carbohydrates and proteins. Thus, it appears that organisms within this order have the potential to utilize a variety of organic wastes and to cost-effectively generate hydrogen.