Marked improvement of anti-N-methyl-D-aspartate receptor encephalitis by large-dose methylprednisolone and plasmapheresis therapy combined with 18F-fluorodeoxyglucose positron emission tomography imaging: A case report.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a recently defined and frequently misdiagnosed disease characterized by psychiatric symptoms, seizures, movement disorders and autonomic dysfunction, has been observed predominantly in young females with ovarian teratoma. Conventional imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), are often ineffective for diagnosis of the disease. If diagnosed early, the initiation of immunotherapy and removal of the tumor (if present) may result in recovery. The current study presents the case of a 38-year-old female with classic clinical symptoms of anti-NMDAR encephalitis. The MRI brain scan results were unremarkable, cerebral spinal fluid (CSF) biochemistry indicated non-specific lymphocytic pleocytosis and the CSF microbiology studies were negative. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging revealed significant generalized asymmetric hypometabolism. The patient demonstrated marked recovery following treatment with a high dose of corticosteroids and plasmapheresis. Accordingly, the follow-up 18F-FDG PET imaging revealed significant improvement.


Longitudinal studies of luteal function by salivary progesterone determinations.
A 'normal range' for salivary progesterone concentrations has been established using data derived from women who were menstruating regularly and in whom dating of the cycle by accepted criteria was possible. Since these values are in agreement with those in the first 9 days of conception cycles and with those in cycles in which ovulation was confirmed by ultrasonography, they provide a reliable index of progesterone output compatible with fertility. Measurement of daily salivary progesterone values in subfertile women for time spans exceeding 3 months allowed accurate assessment of base-line ovarian activity and of the response to ovulation-induction therapy. Salivary sampling, by allowing collection of frequent samples with a minimum of time, stress and inconvenience, is ideally suited to longitudinal studies of ovarian activity. This sampling regimen is also applicable to the monitoring of progesterone output throughout pregnancy.


Headspace solid-phase microextraction for wine volatile analysis.
The most commonly used technique to prepare samples for the analysis of wine volatile is the headspace solid-phase microextraction (HS-SPME). This method has gained popularity in last few years, as it is a unique solventless preparation technique. In this paper, a summary of recently published studies using HS-SPME for the analysis of wine aromas, with special emphasis on the method developed, has been compiled. Several papers are discussed in detail, mainly with respect to the SPME conditions used. A brief summary of the reviews related to HS-SPME analysis is given and discussed. Several parameters affecting the HS-SPME, such as the salt concentration and the agitation conditions, are used in the same way as used in several papers. The HS-SPME extraction proved to be sufficiently sensitive to satisfy legislative requirements related to low detection and quantification limits as well as method accuracy and precision requirements. However, in order to achieve the best performance and precision, the protocol needs to be optimized for each case. The effect of different parameters must be well characterized to ensure correct extraction and desorption to ensure the transfer of extracted compounds into the analytical system. The operating parameters, such as time, temperature, and agitation, must then be kept constant for all the samples.


The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis.
Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 ± 14.2 kPa in F4 disease and 14.6 ± 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 ± 1.2 in F4 disease and 10.3 ± 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, ≥10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, ≥1.80; Fibrotest score, ≥0.54; liver stiffness, ≥23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).


MAGEA11 as a STAD Prognostic Biomarker Associated with Immune Infiltration.
Expression of MAGE family member A11 (MAGEA11) is upregulated in different tumors. However, in gastric cancer, the prognostic significance of MAGEA11 and its relationship with immune infiltration remain largely unknown. The expression of MAGEA11 in pan-cancer and the receiver operating characteristic (ROC) and survival impact of gastric cancer were evaluated by The Cancer Genome Atlas (TCGA). Whether MAGEA11 was an independent risk factor was assessed by Cox analysis. Nomograms were constructed from MAGEA11 and clinical variables. Gene functional pathway enrichment was obtained based on MAGEA11 differential analysis. The relationship between MAGEA11 and immune infiltration was determined by the Tumor Immunity Estimation Resource (TIMER) and the Tumor Immune System Interaction Database (TISIDB). Finally, MAGEA11-sensitive drugs were predicted based on the CellMiner database. The results showed that the expression of MAGEA11 mRNA in gastric cancer tissues was significantly higher than that in normal tissues. The ROC curve indicated an AUC value of 0.667. Survival analysis showed that patients with high MAGEA11 had poor prognosis (HR = 1.43, p = 0.034). In correlation analysis, MAGEA11 mRNA expression was found to be associated with tumor purity and immune invasion. Finally, drug sensitivity analysis found that the expression of MAGEA11 was correlated with seven drugs. Our study found that upregulated MAGEA11 in gastric cancer was significantly associated with lower survival and invasion by immune infiltration. It is suggested that MAGEA11 may be a potential biomarker and immunotherapy target for gastric cancer.


Giant fibrosarcoma arising in dermatofibrosarcoma protuberans on the scalp during pregnancy.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft tissue tumor of subcutaneous tissues that has a propensity for local recurrence; however, it seldom metastasizes. Most lesions occur over the trunk or proximal extremities, and there is slight male preponderance. DFSP is rare on the head and neck. Less than 5% tumors are located on the scalp. To describe a case of giant fibrosarcoma arising in DFSP on the scalp during pregnancy. In our patient, the tumor was on scalp and measured 15 x 11 x 7 cm. The recurrent tumor that developed in the same region was measured 33 x 30 x 15 cm. Histopathologic examination of this mass revealed fibrosarcoma. The mass was excised from the subperiosteal plane with a 3-cm free margin. Because of the high possibility of recurrence, the defect site was reconstructed with a split-thickness skin graft. After 1 year of follow-up, no recurrence or metastasis was detected. We present a unique case in which the person has a giant fibrosarcoma on her scalp arising from DFSP with fibrosarcomatous change during pregnancy.


Improving Physical Therapy Pain Care, Quality, and Cost Through Effectiveness-Implementation Research.
The variability and delay in utilizing evidence in clinical practice are barriers to improving care, quality, and cost in health care, as charged by the "triple aim" framework. Scientific research provides an avenue not only to further the field of pain research, but also to study and change the patterns and processes that drive systemic and individual clinical practices. Implementation science is an emerging field that can be integrated with more traditional effectiveness research to accomplish a combination of aims within the same study. This type of concurrent study of effectiveness and implementation is known as a hybrid design and can be used to improve behavioral or operational practice patterns as well as to collect evidence of clinical effectiveness. Recently, the National Pain Strategy put forth recommendations to improve the care of patients with pain through research and practice. Hybrid designs align well with recent efforts that emphasize value-based, patient-centered health care evolving and described in the National Pain Strategy. The purposes of this perspective are to describe implementation science and hybrid studies and to put forth opportunities to utilize this research to advance the care of patients with pain in the United States.


Transmembrane Protein ANTXR1 Regulates γ-Globin Expression by Targeting the Wnt/β-Catenin Signaling Pathway.
Reactivation of fetal hemoglobin (HbF, α2γ2) alleviates clinical symptoms in patients with β-thalassemia and sickle cell disease, although the regulatory mechanisms of γ-globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated γ-globin levels. However, the exact mechanism by which ANTXR1 regulates γ-globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34+, and HUDEP-2 cells decreased and increased γ-globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, α2γ2) in K562, cord blood CD34+, and adult peripheral blood CD34+ cells through interaction with LRP6 to promote the nuclear entry of β-catenin and activate the Wnt/β-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on γ-globin and Wnt/β-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of β-catenin in the Wnt pathway, but LiCl inhibits GSK3-β. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing γ-globin. Our findings may provide a new intervention target for the treatment of β-hemoglobinopathies.


Speckled lentiginous naevus.
20-year-old male had a spotted discoloured area around the nipple of right breast since early childhood. Histopathologically, it was diagnosed as speckled lentiginous naevus and is reported here for its unusual localisation.


The 12/15-lipoxygenase pathway promotes osteoclast development and differentiation.
Although 12/15-lipoxygenase (12/15-LO) has been implicated as negative regulator of systemic bone mass in mice and humans, the underlying mechanisms remain elusive. Here, we show that 12/15-LO is a positive regulator of osteoclast (OC) development. Enzymatic inhibition as well as genetic ablation of 12/15-LO significantly impaired osteoclastogenesis. Conversely, addition of the 12/15-LO-derived eicosanoids 12- and 15-HETE augmented differentiation of precursors into fully matured OCs. Together these data point towards a crucial role of 12/15-LO in the regulation of OC development. Therefore, 12/15-LO and its human homologue 15-LO may display novel targets for the treatment of diseases such as osteoporosis and rheumatoid arthritis.


Hydrophobicity--shake flasks, protein folding and drug discovery.
Hydrophobic interactions are some of the most important interactions in nature. They are the primary driving force in a number of phenomena. This is mostly an entropic effect and can account for a number of biophysical events such as protein-protein or protein-ligand binding that are of immense importance in drug design. The earliest studies on this phenomenon can be dated back to the end of the 19(th) century when Meyer and Overton independently correlated the hydrophobic nature of gases to their anesthetic potency. Since then, significant progress has been made in this realm of science. This review briefly traces the history of hydrophobicity research along with the theoretical estimation of partition coefficients. Finally, the application of hydrophobicity estimation methods in the field of drug design and protein folding is discussed.


Dihydropyridine binding sites on transverse tubules isolated from triads of rabbit skeletal muscle.
Receptors for the dihydropyridine class of Ca2+ channel antagonists are present on transverse tubules isolated by mechanical disruption of skeletal muscle triads. These observations account for the previously reported presence of nitrendipine binding sites in heavy sarcoplasmic reticulum. Nitrendipine receptors were not found in the terminal cisternae after disruption of the triad junctions. The number of sites in junctional T-tubules (27 pmol/mg) is only half that reported for transverse tubules isolated as free vesicles (pmol/mg). The presence of nitrendipine receptors in that region of the transverse tubules held in close apposition to the SR cisternae is consistent with the architectural requirements for the Ca2+ induced Ca2+ release phenomenon to be the mechanism of excitation-contraction coupling.


Role of the fusion peptide and membrane-proximal domain in HIV-1 envelope glycoprotein-mediated membrane fusion.
The N-terminal fusion peptide and the interfacial sequence preceding the transmembrane anchor of HIV-1 gp41 are required for viral fusion. Studies with synthetic peptides indicated that these regions function by destabilizing membranes, which is regarded as a crucial step in the membrane fusion reaction. However, it is not clear whether membrane destabilization is induced by these sequences in the intact gp41. We address this question by examining fusion and destabilization of membranes expressing HIV-1(IIIB) wild-type Env and two mutant Envs. (1) A Glu residue at position 2 of the gp41 fusion peptide is substituted for Val (V2E) to produce one mutant. (2) Residues 665-682 in the membrane-proximal domain are deleted to form the other. The process of membrane destabilization was monitored by the influx of Sytox, an impermeant fluorescent dye, into the Env-expressing cells following the interaction with CD4-CXCR4 complexes, and fusion was monitored by observing dye transfer between Env-expressing cells and appropriate target cells. We also monitored the conformational changes in the Envs following their interactions with CD4 and CXCR4 by immunofluorescence using an anti-gp41 mAb that reacts with the six-helix bundle. In contrast to the wild type, both Env mutants did not mediate cell fusion. The V2E Env did not mediate membrane destabilization. However, the Env with an unmodified fusion peptide but with a deletion of residues 665-682 in the membrane-proximal domain did mediate membrane destabilization. The wild type and both mutant Envs undergo conformational changes detected by the anti-gp41 six-helix bundle mAbs. Our results suggest that in intact HIV-1 Env the membrane-proximal domain is not required for membrane perturbations, but rather enables the bending of gp41 that is required for viral and target membranes to come together. Moreover, the observation that the Delta665-683 Env self-inserts its fusion peptide but does not cause fusion suggests that self-insertion of the fusion peptide is not sufficient for HIV-1 Env-mediated fusion.


Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c.
In hepatitis C there is controversy over the linearity of the rate of progression and the significance of gender, mode of infection and viral factors. 2313 untreated patients with a reliable estimated duration of infection and liver fibrosis were included. Fibrosis progression was calculated using the Kaplan-Meier method and the rate of fibrosis progression using the hazard function. Seven risk factors were assessed: age at biopsy, gender, alcohol consumption, mode of infection, activity grade, hepatitis C virus genotype and RNA level. The percentage of patients without cirrhosis was 91% after 20 years of infection (95% CI:90-92%) and 56% after 40 years (95% CI:48-64%). Three independent factors were associated (P < 0.001) with a faster progression rate: age at infection, alcohol consumption of 50 g or more per day, and male gender. The mode of infection, histologic activity, genotype and viral load were not independently associated with fibrosis. Fibrosis progression was mainly dependent on age and the duration of infection and can be divided into four successive periods with very slow, slow, intermediate and rapid progression rates. In patients infected with hepatitis C, the majority of fibrosis progression occurred in those aged fifty years or older.


[Leprous neuropathies].
The damage to the peripheral nervous system (PNS) is a marker of Micobacterium leprae (M. leprae) infection that develops as a result of the M. leprae invasion to the Schwann cells. Clinical, functional (skin-deep and stimulating electromyography, determination of the spreading velocity of the pulsatory wave along the arteries of muscle type, direct and volumetric sphingmography, reovasography, skinning electrotermometry) and immunological (evaluation of antibodies to neuroantigenes by ELISA) methods were used to study 132 patients with leprous neuropathy. Sensory impairment (descend of superficial sensibility, combination of the spotted, trunk and polyneuritic types of sensory injury), hypertrophy of the peripheral nerves and their painfulness by palpation were shown to develop at the initial stage, with the following joining of motor and trophic disturbances, such as amyotrophy, contractures, shortening of digits, trophic ulcer. Skin-deep and stimulating electromyography revealed the subclinical manifestation of neuromuscular system injuries in clinically normal muscles. A neuroantigen's entrance into the bloodstream and antibody reactions to them were characteristic of LN. High antibody levels, as a rule, corresponded to the exacerbations of leprous neuropathy, activation of leprous process, relapses of the disease and reactions of leprous erythema nodosum type. An association between specific humoral response to the antigens of the M. leprae and production of the antibodies to neuromarkers was found.


Asymmetrical access to color and location in visual working memory.
Models of visual working memory (VWM) have benefitted greatly from the use of the delayed-matching paradigm. However, in this task, the ability to recall a probed feature is confounded with the ability to maintain the proper binding between the feature that is to be reported and the feature (typically location) that is used to cue a particular item for report. Given that location is typically used as a cue-feature, we used the delayed-estimation paradigm to compare memory for location to memory for color, rotating which feature was used as a cue and which was reported. Our results revealed several novel findings: 1) the likelihood of reporting a probed object's feature was superior when reporting location with a color cue than when reporting color with a location cue; 2) location report errors were composed entirely of swap errors, with little to no random location reports; and 3) both colour and location reports greatly benefitted from the presence of nonprobed items at test. This last finding suggests that it is uncertainty over the bindings between locations and colors at memory retrieval that drive swap errors, not at encoding. We interpret our findings as consistent with a representational architecture that nests remembered object features within remembered locations.


Automatic Guided Waves Data Transmission System Using an Oil Industry Multiwire Cable.
Alternative wireless data communication systems are a necessity in industries that operate in harsh environments such as the oil and gas industry. Ultrasonic guided wave propagation through solid metallic structures, such as metal barriers, rods, and multiwire cables, have been proposed for data transmission purposes. In this context, multiwire cables have been explored as a communication media for the transmission of encoded ultrasonic guided waves. This work presents the proprietary hardware design and implementation of an automatic data transmission system based on the propagation of ultrasonic guided waves using as communication channels a high-temperature and corrosion-resistant oil industry multiwire cable. A dedicated communication protocol has been implemented at physical and data link layers, which involved pulse position modulation (PPM), digital signal processing (DSP), and an integrity validation byte. The data transmission system was composed of an ultrasonic guided waves PPM encoded data transmitter, a 1K22 MP-35N multiwire cable, a hardware preamplifier, a data acquisition module, a real-time (RT) DSP LabVIEW (National Instruments, Austin, TX) based demodulator, and a human-machine interface (HMI) running on a personal computer. To evaluate the communication system, the transmitter generated 60 kHz PPM energy packets containing three different bytes and their corresponding integrity validation bytes. Experimental tests were conducted in the laboratory using 1 and 10 m length cables. Although a dispersive solid elastic media was used as a communication channel, results showed that digital data transmission rates, up to 470 bps, were effectively validated.


Pleiotropic ZmICE1 Is an Important Transcriptional Regulator of Maize Endosperm Starch Biosynthesis.
Starch, the major component of cereal grains, affects crop yield and quality and is widely used in food and industrial applications. The biosynthesis of maize starch is a complex process involving a series of functional enzymes. However, the sophisticated regulatory mechanisms of starch biosynthetic genes have not been fully elaborated. The basic/helix-loop-helix (bHLH) transcription factors are widely distributed in eukaryotes and participate in many physiological processes. In this study, 202 bHLH encoding genes were identified in the maize genome by Blast method. ZmICE1 gene, which belongs to the ICE subfamily of the bHLH family, was obtained and expressed mainly in maize filling endosperm and co-expressed with 14 starch biosynthesis genes. Based on the comparative analyses across different plant species, we revealed that the gene structures and protein domains of the ICE subfamily were conserved between monocots and dicots, suggesting their functional conservation feature. Yeast activation and subcellular localization assays suggested that ZmICE1 had transcriptional activation activity and localized in the nucleus. Yeast one-hybrid assays confirmed that ZmICE1 could directly bind to the promoters of ZmSSIIa and ZmGBSSI. Transient gene expression analysis in maize endosperm revealed that ZmICE1 positively regulated the expression of ZmSSIIa, but inhibited the expression of ZmGBSSI. Our results indicated that ZmICE1 could function as a regulator of maize starch biosynthesis.


The POD: a new model for mentoring underrepresented minority faculty.
Mentoring, long recognized as a catalyst for successful careers, is particularly important to the career development of underrepresented minority (URM) faculty. In academic medicine, mentor-protégé relationships are seriously threatened by increased clinical, research, and administrative demands and an emphasis on scholarship over citizenship. New mentoring models are needed, and they should be adaptable to a medical school's unique structure and mission. The Peer-Onsite-Distance (POD) model, developed in 2002 by the authors and introduced at the College of Medicine at the University of Arkansas for Medical Sciences, is a targeted, multilevel mentoring prototype that is built on a solid research foundation and tailored to the unique needs of URM medical school faculty. The mentee's individual needs for guidance related to career goals, resources, and the content and interaction skills that are known to be critical to successful academic careers are targeted for development. The multilevel approach provides a unique network of peer and faculty mentors who provide site-specific career guidance. Also in the network are leaders in their fields who can provide access to accurate information, cautions, predictions, and announcements of future resources or potential restrictions in academic medicine. Mentor commitments are clearly defined and time contributions are maximized. The POD model aims to promote retention and advance the careers of URM faculty by wrapping them in a protective cushion of interpersonal and intrapersonal support. The flexibility of the design allows for adaptation to any institution's unique structure and mission.


Monteggia Fracture-Dislocation with Associated TFCC Injury and DRUJ Subluxation - A Very Rare Case Report.
Monteggia fracture-dislocation is defined as a proximal third ulna fracture with radiocapitellar joint dislocation. The term "Monteggia equivalent or variant" describes various injuries with similar radiographic patterns and injury biomechanics. Several isolated cases of unusual injuries associated with Monteggia fractures have been reported. However, an associated TFCC injury has not been described in the literature before. We present a rare report of a 24-year-old female with a Monteggia fracture and associated TFCC injury - a crisscross type of injury. A 24-year-old female was involved in a road traffic accident and presented to our level I trauma center with pain and deformity in the left forearm. On evaluation, she was found to have type I Monteggia fracture-dislocation. Intraoperatively, once the proximal ulna was fixed, she had clicking in the wrist during rotations. Fluoroscopic images showed DRUJ subluxation, but it was stable in supination. Hence was splinted in a reduced position. The patient continued to have persistent symptoms in the wrist despite adequate conservative measures. Hence, she underwent arthroscopic TFCC repair and DRUJ pinning. At her last follow-up (3 months), the patient was clinically better with a good range of motion and no pain. In treating Monteggia fracture-dislocations, high index of suspicion is needed to diagnose radioulnar joint instability. If they are missed, they can result in long-term disability, so appropriate evaluation to diagnose TFCC and DRUJ injuries is required. DRUJ stabilization and TFCC repair can produce consistent results when treated adequately.


Human neutrophils produce extracellular traps against Paracoccidioides brasiliensis.
Neutrophils play an important role as effector cells and contribute to the resistance of the host against microbial pathogens. Neutrophils are able to produce extracellular traps (NETs) in response to medically important fungi, including Aspergillus spp., Candida albicans and Cryptococcus gattii. However, NET production in response to Paracoccidioides brasiliensis has yet to be studied. We have demonstrated that human neutrophils produce NETs against both conidia and yeasts of P. brasiliensis. Although the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) did not alter NET production against conidia, it partially suppressed NET formation against P. brasiliensis yeasts. Cytochalasin D or IFN-γ did not affect the production of NETs against the fungus. Additionally, a mutant strain of P. brasiliensis with reduced expression of an alternative oxidase induced significantly higher levels of NETs in comparison with the WT strain. Finally, c.f.u. quantification of P. brasiliensis showed no significant differences when neutrophils were treated with DPI, DNase I or cytochalasin D as compared with untreated cells. These data establish that NET formation by human neutrophils appears to be either dependent or independent of reactive oxygen species production, correlating with the fungal morphotype used for stimulation. However, this mechanism was ineffective in killing the fungus.


Synthesis and characterization of novel hercynite@sulfuric acid and its catalytic applications in the synthesis of polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones.
Herein, we report the synthesis of hercynite@sulfuric acid as a novel nanomagnetic solid acid catalyst, containing the sulfuric acid catalytic sites on the surface of hercynite MNPs as the catalytic support. The as-synthesized nanocomposite was meticulously characterized using a wide range of physicochemical techniques; including, FT-IR, XRD, EDX, X-ray-mapping, SEM and VSM analysis. The catalytic activity of this nanomagnetic material was considered for the synthesis of the diversely substituted polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones under solvent free conditions and also cyclocondensation reactions in ethanol, respectively affording good to excellent yields. Moreover, it is worth mentioning that the heterogeneity of the catalyst was measured through its excellent reusability and hot-filtration test.


FoxO3a governs early microglial proliferation and employs mitochondrial depolarization with caspase 3, 8, and 9 cleavage during oxidant induced apoptosis.
Microglia of the central nervous system have a dual role in the ability to influence the survival of neighboring cells. During inflammatory cell activation, microglia can lead to the disposal of toxic cellular products and permit tissue regeneration, but microglia also may lead to cellular destruction with phagocytic removal. For these reasons, it is essential to elucidate not only the underlying pathways that control microglial activation and proliferation, but also the factors that determine microglial survival. In this regard, we investigated in the EOC 2 microglial cell line with an oxygen-glucose deprivation (OGD) injury model of oxidative stress the role of the "O" class forkhead transcription factor FoxO3a that in some scenarios is closely linked to immune system function. We demonstrate that FoxO3a is a necessary element in the control of early and late apoptotic injury programs that involve membrane phosphatidylserine externalization and nuclear DNA degradation, since transient knockdown of FoxO3a in microglia preserves cellular survival 24 hours following OGD exposure. However, prior to the onset of apoptotic injury, FoxO3a facilitates the activation and proliferation of microglia as early as 3 hours following OGD exposure that occurs in conjunction with the trafficking of the unphosphorylated and active post-translational form of FoxO3a from the cytoplasm to the cell nucleus. FoxO3a also can modulate apoptotic mitochondrial signal transduction pathways in microglia, since transient knockdown of FoxO3a prevents mitochondrial membrane depolarization as well as the release of cytochrome c during OGD. Control of this apoptotic cascade also extends to progressive caspase activation as early as 1 hour following OGD exposure. The presence of FoxO3a is necessary for the expression of cleaved (active) caspase 3, 8, and 9, since loss of FoxO3a abrogates the induction of caspase activity. Interestingly, elimination of FoxO3a reduced caspase 9 activity to a lesser extent than that noted with caspase 3 and 8 activities, suggesting that FoxO3a in relation to caspase 9 may be more reliant upon other signal transduction pathways potentially independent from caspase 3 and 8.


EGFR-TKI resistance and MAP17 are associated with cancer stem cell like properties.
Patients with non-small-cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations generally react well to tyrosine kinase inhibitors (TKIs). However acquired resistance eventually occurs. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification and PIK3CA mutation. In recent years, cancer stem cells (CSCs) have been suggested to be involved in TKI resistance. MAP17 is aberrantly overexpressed in a number of malignancies. However, the expression pattern and function of MAP17 in CSCs are still unclear. The aim the present study was to illustrate the effect of CSC-like cells on the resistance to TKIs in EGFR mutant NSCLC cells and explore the possible role of MAP17 in CSCs. The EGFR mutant cell line PC9 was cultured under serum-deprived undifferentiated conditions. The CSC properties including expression of stem cell markers CD133, CD44, Oct-4 and ABCG2, ability of self-renewal, invasion, proliferation and tumorigenesis were examined. The expression of MAP17 was compared in sphere and parent cells. Sphere cells displayed stem cells phenotypes and were resistant to erlotinib. Sphere cells expressed higher levels of MAP17, and MAP17 was associated with self-renewal and TKI resistance. The function of MAP17 demonstrated to be partially dependent on Na-dependent glucose transporter 1. Collectively these findings suggest that MAP17 serves a role in TKI resistance through regulation of CSCs in lung cancer.


[In hospital and mid-term outcome of patients with NIR stent implantation: multicenter ESPORT-NIR registry].
Despite improvements in the results and techniques of catheter-based revascularization, few studies have evaluated the clinical results of the application of new stent designs. We describe the in-hospital and mid-term outcome of patients undergoing a stent NIR implantation. At least 1 Stent NIR was implanted in 1.004 patients (1.136 lesions) recruited from 50 centers in an international, multicenter, prospective, registry (Spain and Portugal NIR stent registry). Inclusion criteria were objective coronary ischemia related to a severe de novo lesion or first restenosis in native vessels with a reference diameter >= 2.75 mm. The primary end-point was the incidence of major adverse cardiac events within the first 7 months of follow-up. The mean age of the patients was 60 years and 82% were male. Angioplasty was indicated due to unstable angina in 61% of the cases. Stent implantation was successfully achieved in 99.6%. Clinical success (angiographic success without in-hospital major events) was achieved in 98.6% of patients. The rate of angiographic restenosis (> 50% stenosis narrowing) was 16% (CI 95%; 11.7-21.2). The accumulated major cardiac adverse event rate at seven months of follow-up was 8.7%: death (0.9%), acute myocardial infarction (1.2%) and target lesion revascularization (6.6%). In the wide setting of the population included in the ESPORT-NIR registry, stent NIR implantation was a highly effective therapy with a good mid-term clinical and angiographic outcome.


The need for surgery after endoscopic treatment of colorectal neoplasms is the most important outcome criterion.
Endoscopic submucosal dissection (ESD) is known to provide superior results in terms of en bloc and/or R0 resection compared with endoscopic mucosal resection. Therefore, ESD is also expected to provide superior clinical outcomes in terms of the need for supplementary surgery after endoscopic treatment. However, whether or not the clinical gain to the patient is sufficiently large to justify the cost and risk of ESD remains to be further evaluated.


Differences in heart rate variability between Asian and Caucasian children living in the same Canadian community.
Heart rate variability (HRV) is an umbrella term for a variety of measures that assess autonomic influence on the heart. Reduced beat-to-beat variability is found in individuals with a variety of cardiac abnormalities. A reduced HRV positively correlates with obesity, poor aerobic fitness, and increasing age. Racial (black-white) differences are apparent in adults and adolescents. We aimed to evaluate (i) Asian-Caucasian differences in HRV and (ii) differences in HRV between girls and boys. Sixty-two children (30 male (15 Caucasian, 15 Asian) and 32 female (15 Caucasian, 17 Asians)) with a mean age of 10.3 +/- 0.6 y underwent 5 min resting HRV recording, fitness testing (Leger's 20 m shuttle), and self-assessed maturity. Outcome HRV measures were a ratio of low to high frequency power (LF:HF), standard deviation of R-R intervals (SDRR) and root mean square of successive R-R intervals (RMSSD). Data were compared between groups using analysis of covariance (ANCOVA). There were no race or sex differences for time domain variables, mean R-R, body mass index, or blood pressure. Compared with Caucasian children, Asian children displayed a higher adjusted (fitness, R-R interval) LF:HF ratio (72.9 +/- 59.4 vs. 120.6 +/- 85.3, p < 0.05). Girls demonstrated a higher adjusted LF:HF power than boys (117.2 +/- 85.1 vs. 76.6 +/- 62.4, p = < 0.05). In conclusion, Asian and Caucasian children display different frequency domain components of heart rate variability.


Cloning of an aroF allele encoding a tyrosine-insensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase.
In Escherichia coli, genes aroF+, aroG+, and aroH+ encode isoenzymes of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthases that are feedback inhibited by tyrosine, phenylalanine, and tryptophan, respectively. A single base pair change in aroF causes a Pro-148-to-Leu-148 substitution and results in a tyrosine-insensitive enzyme.


Isolation and structure elucidation of a new flavonol glycoside from Sabia Parviflora.
A new flavonol glycoside named Sabiapside A (1), along with four known compounds, quercetin-3-O-gentiobioside (2), camellianoside (3), isobariclisin-3-O- rutinoside (4), tsubakioside A (5), was isolated from Sabia parviflora. Their structures were elucidated by extensive spectroscopic analysis including MS, UV, IR and NMR data. The antioxidant activities of these glycosides evaluated by ABTS+ and DPPH radical scavenging reaction was higher than that of vitamin C used as the reference antioxidant.


Inhibition of postsurgical adhesions by liposomes containing nonsteroidal antiinflammatory drugs.
Intraperitoneal administration of liposomes containing the nonsteroidal antiinflammatory drugs (NSAID) ibuprofen or tolmetin was tested for their efficacy in the prevention of adhesion formation. Both NSAIDs were able to reduce adhesions in an animal model for moderate adhesion formation. However, tolmetin-containing liposomes were more efficacious than ibuprofen-containing liposomes in the reduction of adhesion formation following bilateral uterine abrasion and devascularization surgery.


Probing the chemical functionalization of single-walled carbon nanotubes with multiple carbon ad-dimer defects.
Drying-tube-shaped single-walled carbon nanotubes (SWCNTs) with multiple carbon ad-dimer (CD) defects are obtained from armchair (n,n,m) SWCNTs (n=4, 5, 6, 7, 8; m=7, 13). According to the isolated-pentagon rule (IPR) the drying-tube-shaped SWCNTs are unstable non-IPR species, and their hydrogenated, fluorinated, and chlorinated derivatives are investigated. Interestingly, chemisorptions of hydrogen, fluorine, and chlorine atoms on the drying tube-shaped SWCNTs are exothermic processes. Compared to the reaction energies for binding of H, F, and Cl atoms to perfect and Stone-Wales-defective armchair (5,5) nanotubes, binding of F with the multiply CD defective SWCNTs is stronger than with perfect and Stone-Wales-defective nanotubes. The reaction energy for per F(2) addition is between 85 and 88 kcal mol(-1) more negative than that per H(2) addition. Electronic structure analysis of their energy gaps shows that the CD defects have a tendency to decrease the energy gap from 1.98-2.52 to 0.80-1.17 eV. After hydrogenation, fluorination, and chlorination, the energy gaps of the drying-tube-shaped SWCNTs with multiple CD defects are substantially increased to 1.65-3.85 eV. Furthermore, analyses of thermodynamic stability and nucleus-independent chemical shifts (NICS) are performed to analyze the stability of these molecules.


Very late central nervous system relapse in a patient with B cell lymphoblastic lymphoma.
Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.


Onlay platelet-rich fibrin membrane versus free gingival graft in increasing the width of keratinized mucosa around dental implants: A split-mouth randomized clinical study.
Background. This study aimed to compare the use of the platelet-rich fibrin membrane (PRF) versus the free gingival graft (FGG) during the second stage of the dental implant to increase the amount of keratinized mucosa around dental implants. Methods. Fifteen patients with bilaterally missing teeth and deficient width of the keratinized mucosa (KM) were recruited for a spit-mouth randomized controlled trial. After implant placement on the control sides, onlay FGG was used, whereas, on the other side (study side), onlay PRF membranes were applied to augment the KM. One month and three months after augmentation, the increase in keratinized mucosa width, bone level around the implants, and soft tissue health were evaluated and compared. The shrinkage percentage was also calculated for both grafts. Results. There was a significant increase in the width of KM in the FGG and PRF groups; however, it was observed that FFG resulted in significantly better results than PRF, with no significant difference in peri-implant soft tissue health or bone level. Conclusion. Within the limitations of this study, it was concluded that the onlay PRF membrane could increase the keratinized mucosa width around dental implants with the advantages of a lower surgical time and less postoperative discomfort and pain for the patients in comparison to the FGG. However, FGG had a significantly higher ability to augment and increase keratinized mucosa around dental implants.


The BKT transition and its dynamics in a spin fluid.
We study the effect of particle mobility on phase transitions in a spin fluid in two dimensions. The presence of a phase transition of the BKT universality class is shown in an off-lattice model of particles with purely repulsive interaction employing computer simulations. A critical spin wave region 0 < T < TBKT is found with a nonuniversal exponent η(T) that follows the shape suggested by BKT theory, including a critical value consistent with ηBKT = 1/4. One can observe a transition from power-law decay to exponential decay in the static correlation functions at the transition temperature TBKT, which is supported by finite-size scaling analysis. A critical temperature TBKT = 0.17(1) is suggested. Investigations into the dynamic aspects of the phase transition are carried out. The short-time behavior of the incoherent spin autocorrelation function agrees with the Nelson-Fisher prediction, whereas the long-time behavior differs from the finite-size scaling known for the static XY model. Analysis of coherent spin wave dynamics shows that the spin wave peak is a propagating mode that can be reasonably well fitted by hydrodynamic theory. The mobility of the particles strongly enhances damping of the spin waves, but the model still lies within the dynamic universality class of the standard XY model.


Effect of the canalith repositioning procedure on subjective visual horizontal in patients with posterior canal benign paroxysmal positional vertigo.
Substantial numbers of patients with posterior canal benign paroxysmal positional vertigo (p-BPPV) have signs of utricular dysfunction at baseline. This improves after performing the canalith repositioning procedure. To evaluate the changes of subjective visual horizontal (SVH) in patients with p-BPPV before and after treatment with the canalith repositioning procedure. Twenty-six patients with p-BPPV were treated with the canalith repositioning procedure, Epley's maneuver, according to the affected side. Baseline SVH measurements were taken before performing the Dix-Hallpike maneuver and Epley's maneuver, for comparison with measurements taken just after Epley's maneuver, and 2 weeks after Epley's maneuver. Among 26 patients with p-BPPV, 11 (42%) showed abnormal deviation of SVH at baseline. Just after performing Epley's maneuver, the number of patients who showed an abnormal deviation of SVH decreased significantly to 15% (4 of 26 patients; p < 0.05). Two weeks after performing Epley's maneuver, only two patients (8%) showed an abnormal deviation of SVH (p < 0.001).


Triple mediation of attitude to bridge transformational leadership on organizational citizenship behavior.
This study was conducted to determine the Organizational Citizenship Behavior (OCB) of correctional officers at the Super Maximum-Security Prison in Indonesia which is influenced by Transformational Leadership (TL) either directly or indirectly through Affective Organizational Commitment (AOC), Job Satisfaction (JS) and Job Self-Efficacy (JSE). This research was conducted on 224 prison officers as a sample size. Data was collected by means of a questionnaire distributed via Google Form. Robustness was built in two stages; the first stage was through a try out of research instruments and the second stage was through data collection which was done with the time lagged method. Furthermore, the data were analyzed using Structural Equation Modeling (SEM) with the help of AMOS 24 software. The results of this study indicate that triple mediation consisting of AOC, JS and JSE fully mediates the effect of TL on OCB. The novelty of this research lies in the role of triple mediation as the focuses of the study. Furthermore, the triple mediation has been proven to fully mediate the effect of TL on OCB thus may serve as empirical evidence that contribute to theoretical and practical developments in the fields of Human Resource Management and Organizational Behavior.


Assessment of fever in African children: implication for malaria trials.
We evaluated methods for assessing body temperature by comparing subjective assessment of fever by parents and doctors with objective axillary, tympanic, and rectal measurements of body temperature in 1000 children < or = 10-years-old who presented at outpatient clinics with recent history of fever. Sensitivity of subjective assessment of fever were higher at thresholds of > or = 38.3 degrees C with specificity as low as 60%. Axillary methods showed better specificity at fever thresholds of > 38.0 degrees C with maximum sensitivity of 63% at thresholds of > or = 37.5 degrees C. Bland-Altman analysis showed wide limits of agreement between objective methods of measurements: -1 degrees C to 3 degrees C for comparison of rectal and axillary, -1 degrees C to 2 degrees C for rectal and tympanic, and -1 degrees C to 2 degrees C for tympanic and axillary measurements. A choice of method to measure body temperature for diagnosis of fever in African children should be informed by a trade-off between its specificity and sensitivity that considers thresholds > 38.0 degrees C.


Taurine alleviates lipopolysaccharide‑induced liver injury by anti‑inflammation and antioxidants in rats.
The aim of the present study was to investigate the protective effect of taurine on lipopolysaccharide (LPS)‑induced liver injury and its mechanisms. Male rats were randomly divided into three groups: Normal saline, LPS model and taurine treatment. Experimental animals were treated with saline or taurine (dissolved in saline, 200 mg/kg/day) via intravenous injection. After 2 h, saline or LPS (0.5 mg/kg) was administrated via intraperitoneal injection. Markers of liver injury, pro‑inflammatory cytokines and superoxide dismutase (SOD) activity were determined in plasma. Liver tissues were removed for morphological analysis and determination by western blot analysis. Taurine significantly reduced the elevation in the levels of LPS‑induced aspartate transaminase and alanine transaminase and decreased the concentrations of LPS‑induced inflammatory factors including tumor necrosis factor‑α and interleukin‑6. Taurine also increased the activity of SOD in serum and the expression of heme oxygenase‑1 protein in liver tissue. Taurine pretreatment also reduced the elevated expression levels of LPS‑induced cyclooxygenase‑2, nuclear factor κB and extracellular regulated protein kinase. The results from the present study demonstrated that taurine alleviates LPS‑induced liver injury. The beneficial role of taurine may be associated with its reduction of pro‑inflammatory response and oxidative stress.


Sebaceous Carcinoma of the Face Treated With Mohs Micrographic Surgery.
Mohs micrographic surgery (MMS) for sebaceous carcinoma (SC) may reduce local recurrence rates, but published case series have small cohorts and limited follow-up. Mohs micrographic surgery is particularly suitable for sensitive functional and cosmetic locations, such as the face, because it facilitates tissue conservation using complete peripheral and deep margin assessment before reconstruction. Coordinated care between Mohs and oculoplastic surgeons has not been described. To assess rates of local recurrence and metastasis after MMS of facial SC and to describe coordinated care between Mohs and oculoplastic surgeons. Retrospective review identified facial SC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded. Descriptive and predictive analyses were performed. Forty-nine cases were reviewed with a mean follow-up of 51 months. The most common sites were periorbital, infraorbital cheek, and nasal ala. No patients experienced regional recurrence after MMS. One patient with Muir-Torre syndrome developed metastatic recurrence (at 82.9 months). All patients underwent 2-stage reconstruction with dermatology-performed MMS and oculoplastic reconstruction. Collaboration between Mohs and oculoplastic surgeons with a tissue-sparing approach of MMS can reduce recurrence and optimize cosmesis and function for central facial SC.


Accidental and potentially life-threatening finding: pulsatile mass of the hypopharynx.
Anatomical variations of the cervical part of the internal carotid artery (ICA) are not rare in the general population. They are usually asymptomatic and more common in the elderly. We report the case of a 70-year-old Caucasian woman who was referred to our department due to chronic cough. We performed a flexible nasofibrolaryngoscopy that demonstrated the presence of a pulsatile mass in the hypopharynx. After performing a cervical contrast-enhanced CT, the mass turned out to be an aberrant variation of the cervical part of the ICA. This case is intended to alert otolaryngologists, anaesthesiologists, radiologists and surgeons for this accidental finding and the possible consequences for the patient if not diagnosed and properly oriented.


Metal-independent reduction of hydrogen peroxide by semiquinones.
The quinones 1,4-naphthoquinone (NQ), tetramethyl-1,4-benzoquinone (DQ), 2-methyl-1,4-naphthoquinone (MNQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UBQ-0), 2,6-dimethylbenzoquinone (DMBQ), 2,6-dimethoxybenzoquinone (DMOBQ), and 9,10-phenanthraquinone (PHQ) enhance the rate of H2O2 reduction by ascorbate, under anaerobic conditions, as detected from the amount of methane produced after hydroxyl radical reaction with dimethyl sulfoxide. The amount of methane produced increases with an increase in the quinone one-electron reduction potential. The most active quinone in this series, PHQ, is only 14% less active than the classic Fenton reagent cation, Fe(2+), at the same concentration. Since PHQ is a common toxin present in diesel combustion smoke, the possibility that PHQ-mediated catalysis of hydroxyl radical formation is similar to that of Fe(2+) adds another important pathway to the modes in which PHQ can execute its toxicity. Because quinones are known to enhance the antitumor activity of ascorbate and because ascorbate enhances the formation of H2O2 in tissues, the quinone-mediated reduction of H2O2 should be relevant to this type of antitumor activity, especially under hypoxic conditions.


Experimental study of endurance characteristics of Al-doped HfO2ferroelectric capacitor.
In this work, the endurance characteristics of Al-doped HfO2(HAO)-based metal-ferroelectric-metal (MFM) capacitors (which were annealed at 1000 °C) with various doping concentrations were investigated. The doping concentration was optimized for the high annealing temperature (1000 °C) process. To investigate the impact of cycling pulses on the endurance characteristics of HAO-based MFM capacitor, the rise/fall time (tr/f) and hold time (th) for the cycling pulses were varied. Moreover, by adopting the recoverable fatigue process, the endurance characteristics under repetitive wake-up/fatigue processes were studied. The HAO capacitors achieved the remnant polarization (2Pr) of 23.767μC cm-2at pristine state under the high annealing temperature. Furthermore, it was demonstrated that the endurance characteristics (∼108cycles) of the HAO capacitors were comparable to them of other HfO2-based ferroelectric capacitors. Lastly but not least, it turned out that the amount of oxygen and oxygen vacancies in the HAO thin film was dependent of doping concentrations for the film. The impact of oxygen and oxygen vacancies was quantitatively analyzed, in detail, with TEM, XPS and GIXRD analysis.


[HLA typing in a neonate with posttransfusional graft vs host disease (PT-GVHD)].
The authors report a case of post-transfusion-graft-versus-host disease (PT-GVHD) in a premature infant after parental blood donation. This disease seems to be due to the transfusion of immunocompetent T lymphocytes into an immunodeficient recipient or into an immunocompetent host who shares an HLA haplotype with HLA-homozygous blood donors (i.e. relatives or members of inbred populations) and who is therefore unable to reject the graft cells. The results of HLA typing of the patient and his family demonstrated that the infant was identical with his father for HLA class II antigens (DR, DQ) and, concerning HLA class I, he had in common the remaining paternal haplotype (A29, B44). Prevention of this disease, performed by gamma irradiation of blood components before transfusion, appears to be effective in most cases.


Ubiquitous observations of enhanced solid affinities for aromatic organochlorines in field situations: are in situ dissolved exposures overestimated by existing partitioning models?
This paper investigates the ability of the traditional organic matter partitioning (OMP) model to predict the solid-water distribution, and hence the dissolved exposures, of hydrophobic organic compounds (HOCs) in real field situations. Observed organic-carbon-normalized partitioning coefficients (Koc)obs) of polychlorinated biphenyls, polychlorinated benzenes, polychlorinated dibenzo-dioxins and -furans, and p,p'-dichlorodiphenyltrichlorethane (DDT) with metabolites were selected from the literature and compared with their respective OMP model estimates. For all compound classes and in a majority of the investigated cases, (Koc)obs values were significantly larger than predicted. This translated into factors of overestimated dissolved exposures ranging from 1 to 1,000. Various reasons are discussed for the discrepancies between predictions and actual observations, such as the effect of the diagenetic state and other properties of the particulate organic matter. The greater enhancement in (Koc)obs of planar over nonplanar compounds suggests in certain cases that efficient interactions with aromatic soot phases may be significant. For an improved predictability of (Koc)obs and dissolved exposures of HOCs in the real environment, the inclusion of soot and possibly other distinct subfractions of bulk organic carbon into an extended solid-water partitioning model may be considered.


Reliability and validity of the Chinese Depression Adjective Check Lists.
Presented data on the translation and on the reliability and concurrent validity of the Chinese version of the Depression Adjective Check Lists (DACL). Reliability and validity coefficients are significant and of sufficient magnitude to warrant their use in research (N = 37).


Artificial intelligence for predicting five-year survival in stage IV metastatic breast cancer patients: A focus on sarcopenia and other host factors.
We developed an artificial intelligence (AI) model that can predict five-year survival in patients with stage IV metastatic breast cancer, mainly based on host factors and sarcopenia. From a prospectively built breast cancer registry, a total of 210 metastatic breast cancer patients were selected in a consecutive manner using inclusion/exclusion criteria. The patients' data were divided into two categories: a group that survived for more than 5 years and a group that did not survive for 5 years. For the AI model input, 11 features were considered, including age, body mass index, skeletal muscle area (SMA), height-relative SMA (H-SMI), height square-relative SMA (H2-SMA), weight-relative SMA (W-SMA), muscle mass, anticancer chemotherapy, radiation therapy, and comorbid diseases such as hypertension and mellitus. For the feature importance analysis, we compared classifiers using six different machine learning algorithms and found that extreme gradient boosting (XGBoost) provided the best accuracy. Subsequently, we performed the feature importance analysis based on XGBoost and proposed a 4-layer deep neural network, which considered the top 10 ranked features. Our proposed 4-layer deep neural network provided high sensitivity (75.00%), specificity (78.94%), accuracy (78.57%), balanced accuracy (76.97%), and an area under receiver operating characteristics of 0.90. We generated a web application for anyone to easily access and use this AI model to predict five-year survival. We expect this web application to be helpful for patients to understand the importance of host factors and sarcopenia and achieve survival gain.


Reformulation and Priorities for Reducing Energy Density; Results from a Cross-Sectional Survey on Fat Content in Pre-Packed Cakes and Biscuits Sold in British Supermarkets.
Cakes and biscuits contribute to energy, total and saturated fat and sugar in British diets. So far, the UK government has prompted manufacturers to reduce energy density in these products through a reduction of their sugar content. We conducted a cross-sectional survey of the fat content of cakes and biscuits available in nine UK supermarket chains. In cakes (n = 381), the mean total fat content was 17.9 ± 5.2 g/100 g (39% of the overall energy); range (1.4-35.6 g/100 g) and the average saturated fat content in cakes was 5.9 ± 3.4 g/100 g (13% of the overall energy); range (0.3-20 g/100 g). In biscuits (n = 481), the mean total fat content was 21.8 g ± 6.3 g/100 g (40% of the overall energy); range (0.7-38.9 g/100 g) and the average saturated fat content was 11.4 ± 4.9 g/100 g (23% of the overall energy); range (0.3-22.3 g/100 g). In both cakes and biscuits, total and saturated fat content was positively correlated with energy density. Our results show that cakes and biscuits sold in UK supermarkets are high in total and saturated fat, and that fat content contributes substantially to product energy density. Fat reformulation in these products would effectively reduce energy density, calorie intake and help prevent obesity. Fat reformulation should be implemented simultaneously with sugar reformulation and be focused on saturated fat, as this will have the additional effect of lowering LDL cholesterol.


[The Molecular Switches and Atomic Biological Mechanisms Underlying the Physiological and Pathophysio-logical Effects of Hydrogen Sulfide to Regulate Its "Receptors"].
Hydrogen sulfide (H2S)has emerged as pivotal signaling molecules since it is recognized as the third gasotransmitter together with nitric oxide and carbon monoxide. The development of detecting technologies contributed to the research in H2S biology.H2S plays significant roles in human body systems, such as the cardiovascular system, nervous system, respiratory system etc.. Alterations of H2S concentrations have been connected with many diseases. Hypertension, atherosclerosis, neurodegenerative disorder, asthma and many other diseases are found to be related with abnormal H2S metabolism. It has become a potential drug for therapeutic purposes. Understanding the mechanism of H2S biology, including a molecular switch contained in its "receptor", has deepened the research on how small molecules regulate big molecules, as well as providing new strategy for the therapeutic approaches for varies of diseases.


Spectrum of Pitfalls, Pseudolesions, and Potential Misdiagnoses in Cirrhosis.
The purposes of this article are to review a variety of pitfalls in liver imaging that can lead to the inaccurate diagnosis of focal hepatic lesions in cirrhosis, to describe the pathophysiologic processes of these pitfalls, and to provide specific clues for achieving the correct diagnoses. Cirrhosis complicates liver imaging. The distortion and replacement of normal liver parenchyma by fibrous and regenerative tissue can change the typical appearance of many benign lesions, causing them to be misinterpreted as malignancy. In addition, the high incidence and prevalence of hepatocellular carcinoma among patients with cirrhosis put radiologists on high alert for any suspicious findings, especially because not all hepatocellular carcinomas have a typical imaging appearance.


Methodological Approaches to Study Extracellular Vesicle miRNAs in Epstein⁻Barr Virus-Associated Cancers.
Epstein Barr-virus (EBV) was the first virus identified to be associated with human cancer in 1964 and is found ubiquitously throughout the world's population. It is now established that EBV contributes to the development and progression of multiple human cancers of both lymphoid and epithelial cell origins. EBV encoded miRNAs play an important role in tumor proliferation, angiogenesis, immune escape, tissue invasion, and metastasis. Recently, EBV miRNAs have been found to be released from infected cancer cells in extracellular vesicles (EVs) and regulate gene expression in neighboring uninfected cells present in the tumor microenvironment and possibly at distal sites. As EVs are abundant in many biological fluids, the viral and cellular miRNAs present within EBV-modified EVs may serve as noninvasion markers for cancer diagnosis and prognosis. In this review, we discuss recent advances in EV isolation and miRNA detection, and provide a complete workflow for EV purification from plasma and deep-sequencing for biomarker discovery.


Data-Driven Derivation of Molecular Substructures That Enhance Drug Activity in Gram-Negative Bacteria.
The complex cell envelope of Gram-negative bacteria creates a formidable barrier to antibiotic influx. Reduced drug uptake impedes drug development and contributes to a wide range of drug-resistant bacterial infections, including those caused by extremely resistant species prioritized by the World Health Organization. To develop new and efficient treatments, a better understanding of the molecular features governing Gram-negative permeability is essential. Here, we present a data-driven approach, using matched molecular pair analysis and machine learning on minimal inhibitory concentration data from Gram-positive and Gram-negative bacteria to uncover chemical features that influence Gram-negative bioactivity. We find recurring chemical moieties, of a wider range than previously known, that consistently improve activity and suggest that this insight can be used to optimize compounds for increased Gram-negative uptake. Our findings may help to expand the chemical space of broad-spectrum antibiotics and aid the search for new antibiotic compound classes.


Solid malignancies complicated with pulmonary embolism: clinical analysis of 120 patients.
Pulmonary embolism, a potentially fatal event, occurs more frequently in cancer patients than in the general population. To offer an accurate diagnosis and effective treatment to such patients in China, we analyzed the incidence rate and clinical features of pulmonary embolism in patients with solid tumor hospitalized in the Peking Union Medical College (PUMC) Hospital. A retrospective analysis was made of the hospitalized patients with solid malignancies complicated with pulmonary embolism who had been admitted into the PUMC Hospital from January 2002 to December 2008. The incidence of pulmonary embolism in hospitalized patients with solid malignancies was 0.27% (120/43 967). The median age at diagnosis was 57.5 years. The male to female ratio was 1.0:1.4 (49:71). Patients with non-small-cell lung cancer (NSCLC) constituted the largest proportion of the 120 patients (37.5%), followed by patients with breast (9.2%), ovarian (8.3%), pancreatic (6.7%), and liver cancer (6.7%). Eighty patients (66.7%) had stage IV cancer. Bone was the most common site of distant metastasis (46.3%). D-dimer level was elevated in 90.9% of the 66 tested patients. The incidence of bleeding due to anti-coagulation therapy was 3.6%. Thirty-six (30.0%) of the 120 patients had concurrent deep venous thrombosis in the lower extremities. Seventeen patients developed acute pulmonary embolism within 2 weeks after surgery, 3 of whom died suddenly. Four patients presented with deep venous thrombosis and 1 with pulmonary embolism prior to the identification of malignancy. Patients with cancer of the lung, ovarian, breast, pancreas, and liver are more likely to be complicated with pulmonary embolism than those with other types of solid tumors. Patients with distant metastasis are at a higher risk of pulmonary embolism. Pulmonary embolism without concurrent deep venous thrombosis is more frequently observed than concurrence of both disorders in the clinical setting.


Quantitative assessment of fibrosis in liver biopsies from patients with chronic hepatitis B.
Accurate histological assessment of liver fibrosis is essential in the management of chronic hepatitis B (CHB). Although semi-quantitative scoring systems describe well the pathological patterns of hepatic structure, they produce fibrosis evaluation that is not very precise. Image analysis or morphometry has the theoretical advantage of providing truly quantitative data. The present study aimed at validating a new image analysis system, Bioquant Nova Prime, in estimating collagen content in liver biopsy samples from patients with CHB. The biopsies were stained with picrosirius red and the areas of collagen were measured. The results were correlated with laboratory parameters and Ishak modified histological scores. Discriminative reliability of morphometry was determined using receiver operating characteristics (ROC) analysis. There was excellent interobserver agreement (r=0.84-0.94, P<0.01) in the morphometric analysis. Significant correlations between the quantitative morphometric data and the semi-quantitative score (Spearman's r=0.68-0.78, P<0.001) were also demonstrated. Excellent discriminative power of morphometry in differentiating mild from advanced fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis. Our results validated the use of Bioquant Nova Prime in estimating collagen content in liver biopsies. We showed that morphometry is a sensitive method of liver fibrosis quantification in CHB and complements semi-quantitative histological scoring system. This tool, with its reliable intraassay variability, could be of special value in assessing histological response to treatment after anti-viral or anti-fibrotic therapy.


[Annual self-assessment of perioperative complications and early success: the best way to improve the medical results in the Vascular Surgery Department].
In spite of many recent advances, vascular surgery is still weighed down with serious complications which occur in 1 to 5% of open surgery cases and 0 to 2% of endovascular cases. Some of them are due to the specific characteristics of atherosclerotic and aneurysmal diseases; others are associated with the technics of arterial reconstructions; but others are surgeon-dependant as their rate vary from on center to another. Quality of results depend on the experience of one surgeon and his team. This experience is based on an unquantified analysis of past success and failures. However currently, it is necessary to take in account the scientific guidelines as well as the personal results of the surgical team. The latter are known only when they are periodically checked in a systematic process. We report a 23 years experience of annual self assessment of the perioperative complications covering all the arterial reconstructions performed during the previous year. These evaluation had five effects: they linked the physicians and nurses in the quest of optimal efficacy; they focused all the team on the cares and results which needed to be improved; complications and success rates were a guide for the therapeutic choices; reliable results rates allowed a precise information of patients, hospital-managers and lawyers when necessary; they were one of the most important factors of continuing medical education. No other mean can replace these self-assessment procedures: retrospective studies are focused on limited areas; mortality-mobidity conferences are devoted to the recent complications without statistical analysis; the PMSI is directed towards cost-containment rather than quality of results. When a team do not know which results are poor, it is unlikely that they will be improved. We hope that the hospital accreditation which has been introduced in France in 1996, will make mandatory the practice of mortality-morbidity conferences, annual evaluation of perioperative complications and periodic studies of long term results. For medical and economical reasons, the population may require that we systematically monitor our results and take them in account before deciding a treatment. Physicians who are unaware of there own results cannot inspire confidence.


Polyamines regulate gap junction communication in connexin 43-expressing cells.
The control of cell-cell communication through gap junctions is thought to be crucial in normal tissue function and during various stages of tumorigenesis. However, few natural regulators of gap junctions have been found. We show here that increasing the activity of ornithine decarboxylase, or adding polyamines to the outside of cells, increases the level of gap junction communication between various epithelial cells. Conversely, reduction of ornithine decarboxylase activity decreases the level of gap junction communication. This regulation is dependent upon the expression of connexin 43 (Cx43 or Cxalpha1), which is a major connexin expressed in many different cell types, and involves an increase in Cx43 and its cellular re-distribution.


Personal and Political: Post-Traumatic Stress Through the Lens of Social Identity, Power, and Politics.
Post-traumatic stress disorder (PTSD) has always been controversial and highly politicized. Here, using a social identity approach, we review evidence that trauma and its aftermath are fundamentally linked to social position, sociopolitical capital, and power. We begin this contribution by demonstrating how a person's group memberships (and the social identities they derive from these memberships) are inherently linked to the experience of adversity. We then go on to consider how it is through group memberships that individuals are defined by their trauma risk and trauma histories-that is, a person's group memberships and their trauma are often inherently linked. Considering the importance of group memberships for understanding trauma, we argue that it is important to see these, and group processes more generally, as more than just "demographic" risk factors. Instead, we argue that when groups are defined by their trauma history or risk, their members will often derive some sense of self from this trauma. For this reason, attributes of group memberships are important in developing an understanding of adjustment and adaptation to trauma. In particular, groups' status, their recourse to justice, and the level of trust and solidarity within the group are all central to the impact of traumatic events on individual-level psychological resilience. We review evidence that supports this analysis by focusing on the exacerbating effects of stigma and social mistrust on post-traumatic stress, and the value of solidarity and strong identities for resilience. We conclude that because of these group-related processes, trauma interweaves the personal with the political and that post-traumatic stress is fundamentally about power, positionality, and politics.


[Complications associated with the surgical treatment of acetabular fractures].
To analyse retrospectively complications of the surgical treatment of displaced acetabular fractures. In the years 1996 to 2006 a total of 251 patients with acetabular fractures were treated. The group comprised 162 men and 89 women; the average age was 35 years. The average follow-up was 71 months (range, 16 to 138). Based on the AO classification, type A fractures were found in 58%, type B in 23% and type C in 19% of the patients. Indications for surgical intervention were hip instability or hip incongruence. The complications included intra-operative, and early and late post-operative problems. Of the intra-operative complications, 2% were vascular injuries, 5% were damage to the static nerve, 13% were due to incomplete reduction and 2% due to bone non-union. Early post-operative complications in five patients (2%) required revision surgery for early infection in two, haematoma in the wound in one and failed osteosynthesis in two patients. In one patient failed osteosynthesis was associated with hip dislocation. Late complications included aseptic necrosis in 7%, post-traumatic arthritis in 17%, para-articular ossification grades III and IV of the Brooker classification in 7% and late infection in 0.5% of the patients. The outcome of surgical treatment depends on quality reconstruction of the articular surface and complications, and is related to the fracture type and method of treatment. Not every poor outcome means it is a complication, nor is it always related to the type of fracture. Some fracture types are bound to heal poorly. The complex anatomy of the joint involves rather frequent injury to nerve structures and imperfect reduction and fixation. The most frequent complication is the development of post-traumatic arthritis due to imperfect reduction. However, the current limit of achieving correct reduction and weight-bearing surface reconstruction remains an open issue. Aseptic necrosis in type A fractures was three-times as high as in type B and C fractures. Imperfect reconstruction of the acetabulum and failure to restore hip joint congruence were twice higher in type B than type A and C fractures.


Incidence and survival of pancreatic head and body and tail cancers: a population-based study in the United States.
Cancer of the body/tail of the pancreas is frequently separated from pancreatic head tumors. No studies have examined whether the demographics, disease characteristics, and patient survival with pancreatic body/tail cancers are different from pancreatic head tumors. We used the Surveillance, Epidemiology, and End Results (SEER) registry to identify 43,946 cases of pancreatic cancer. The yearly incidence and survival rates were calculated. Cox proportional hazards model examined temporal trends in survival. The incidence rate for pancreatic head cancer has remained at 5.6% per 100,000, whereas the rate for pancreatic body/tail cancers has increased by 46% between 1973 and 2002. The 3-year survival rate has increased slightly for both groups. The Cox proportional hazards model analysis confirms this improvement. The 3-year survival rate for local-stage pancreatic body/tail cancer is 20.0% compared with 9% for local-stage pancreatic head cancer. This study indicates that the incidence of pancreatic head cancer has remained stable, whereas the incidence of pancreatic body/tail cancers is rising. Despite higher survival rates among patients with pancreatic head cancer compared with those with pancreatic body/tail cancers in several variables, patients with local-stage pancreatic body/tail cancers had higher survival rates compared with local-stage pancreatic head cancer.


Coverage dependence of the adsorption structure of alanine on Ge(100).
The variations with coverage and annealing temperature in the adsorption structure of alanine on Ge(100) have been investigated using high-resolution core-level photoemission spectroscopy (HRCLPES). The C 1s, N 1s, and O 1s core-level spectra at a low initial coverage show that both the carboxyl and amine groups of the alanine molecules participate in bonding with the Ge(100) surface in an "intrarow O-H dissociated and N dative bonded structure". However, at higher coverage we found that in addition to this structure an "O-H dissociation structure" is present. Moreover, we systematically monitored the variation of the bonding features of alanine adsorbed on Ge(100) with annealing temperature and thus were able to track the desorption processes. By analyzing the C 1s, N 1s, and O 1s spectra at 420 K, we conclude that the principal adsorption structure at this temperature is the "O-H dissociation structure" because of the disconnection of Ge-N dative bonding. At higher temperatures, the "O-H dissociation structure" is converted into various fragments such as Ge oxide (or Ge-CO), Ge nitride (Ge cyanide), and Ge carbide.


NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats.
Among the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the administration of eye drops containing NGF (ed-NGF) to adult Sprague Dawley rats receiving streptozotocin (STZ) intraperitoneal injection was used as an experimental paradigm to investigate NGF modulation of VEGFA and its receptor VEGFR2 expression. We show that ed-NGF treatment prevents the histological and vascular alterations in STZ retina, VEGFR2 expression decreased in GCL and INL, and preserved the co-expression of VEGFR2 and NGF-tropomyosin-related kinase A (TrkA) receptor in retinal ganglion cells (RGCs). The WB analysis confirmed the NGF effect on VEGFR2 expression and activation, and showed a recovery of VEGF isoform dysregulation by suppressing STZ-induced VEGFA121 expression. Reduction in inflammatory and pro-apoptotic intracellular signals were also found in STZ+NGF retina. These findings suggest that ed-NGF administration might favor neuroretina protection, and in turn counteract the vascular impairment by regulating VEGFR2 and/or VEGFA isoform expression during the early stages of the disease. The possibility that an increase in the NGF availability might contribute to the switch from the proangiogenic/apoptotic to the neuroprotective action of VEGF is discussed.


Carotid plaque characterization by magnetic resonance imaging: review of the literature.
Magnetic resonance imaging (MRI) of carotid plaque has undergone significant improvements in the last decade. Early studies utilizing ex vivo specimens and spin-echo or fast spin-echo imaging led to the conclusion that T2 weighting is the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2-weighted signal intensities among the various plaque components, which can be partially offset by the use of multispectral analysis of multiple contrast images. With improvements in coil design, sequence design, and main field and gradient capabilities, accurate in vivo differentiation and measurement of these various carotid plaque components should be possible in 3 to 5 years. Ex vivo and in vivo studies have yielded high-resolution measurements of the complex three-dimensional lumen geometry, which are being used to predict hemodynamic forces acting on the lumenal surface. Carotid plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MRI of the diseased carotid artery wall may prove to be even more important than magnetic resonance angiography.


A case series of Vibrio vulnificus infections in New Orleans, Louisiana.
The objective of this study is to describe cases of V. vulnificus infection and to review the literature, emphasizing salient aspects of infection for practicing physicians. A retrospective review of all patients aged 5 years and older who grew V. vulnificus from a blood or tissue culture from 2005 to 2011 at Tulane University Medical Center and Interim Louisiana Public Hospital. Six patients were identified over the study period. All were male and had a history of liver disease. Four developed primary septicemia and two developed wound infection with secondary septicemia. One received doxycycline as part of his antimicrobial therapy, which along with ceftazidime, is the recommended therapy for V. vulnficus infection. Four patients died despite aggressive care. V. vulnificus infection is an uncommon but often fatal cause of severe sepsis and wound infection. Physicians must recognize the clinical presentations of this infection in order to initiate early and appropriate therapy.


A computer-aided tool for automatic volume estimation of hematoma using non-contrast brain CT scans.
The computation of hematoma volume is the key parameter for treatment planning of Intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) imaging is routinely used for the diagnosis of ICH. Hence, the development of computer-aided tools for three-dimensional (3D) computed tomography (CT) image analysis is essential to estimate the gross volume of hematoma. We propose a methodology for automatic estimation of the hematoma volume from 3D CT volumes. Our approach integrates two different methods, multiple abstract splitting (MAS) and seeded region growing (SRG) to develop a unified hematoma detection pipeline from pre-processed CT volumes. The proposed methodology was tested on 80 cases. The volume was estimated from the delineated hematoma region, validated against the ground-truth volumes, and compared with those obtained from the conventional ABC/2 approach. We also compared our results with the U-Net model (supervised technique) to show the applicability of the proposed method. The volume calculated from manually segmented hematoma was considered the ground truth. TheR2correlation coefficient between the volume obtained from the proposed algorithm and the ground truth is 0.86, which is equivalent to theR2value resulting from the comparison between the volume calculated by ABC/2 and the ground truth. The experimental results of the proposed unsupervised approach are comparable to the deep neural architecture (U-Net models). The average computation time was 132.76 ± 14 seconds. The proposed methodology provides a fast and automatic estimation of hematoma volume, which is similar to the baseline user-guided ABC/2 approach. Implementation of our method does not demand a high-end computational setup. Thus, recommended in clinical practice for computer-assistive volume estimation of hematoma from 3D CT volumes and can be implemented in a simple computer system.


Potato purple top disease associated with the novel subgroup 16SrII-X phytoplasma.
Potato (Solanum tuberosum) is a very economically important perennial tuberous crop in Saudi Arabia. Potato plants displaying symptoms associated with potato purple top disease, such as aerial tubers and purple and small leaves, were observed in Al-Bukairiyah, Fowlq and Buraydah, Al-Tarafiyah, Qassim governorate, Saudi Arabia. In this study, we examined samples taken from 12 symptomatic potato plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA-encoding sequences revealed that the symptomatic plants were infected with phytoplasma belonging to the peanut witches'-broom group (16SrII). Sequencing of the 16S rRNA- encoding gene, computer-simulated RFLP analysis and phylogenetic analysis revealed the presence of a novel representative of the 16SrII-X subgroup. The present study identified potato plants as a novel host for novel phytoplasma strains belonging to the pigeon pea witches'-broom group in Saudi Arabia.


Detection of initiation activity of 1,2-dimethylhydrazine in in vivo medium-term liver initiation assay system using 4-week-old rats without hepatocellular proliferative stimuli during the test chemical treatment period.
We have developed an in vivo medium-term liver initiation assay system to detect initiation activities of chemicals on multi-organ carcinogenesis. However, cell proliferation stimuli during the test chemical treatment period, required in the previously used assay models using adult rats, are laborious; moreover, those cause decrease of hepatic metabolic enzymes and psychological and physical discomfort to animals resulting in inaccurate interpretation. Therefore, we investigated the utility of another in vivo medium-term liver initiation assay model using 4-week-old rats without the cell proliferation stimuli. In this study, we confirmed that 4-week-old and 4.5-week-old male rats have high hepatocyte proliferation activity and similar enzyme activities of hepatic Cytochrome P450 subtypes as compared with 8-week-old male rats. Next, the in vivo medium-term liver initiation assay model using 4-week-old rats without cell proliferation stimuli was evaluated for the detection of the initiation activity of 1,2-dimethylhydrazine (DMH), which is a well-known genotoxic carcinogen. Four-week-old rats were orally administered DMH (single dose, 4 or 16 mg/kg; or 4-day repeat, 1 or 4 mg/kg); subsequently, these rats were treated promotion treatment consisted of administration of 2-acetylaminofluorene and carbon tetrachloride. Four weeks after the first DMH administration, the glutathione S-transferase placental form (GST-P)-positive foci induced by DMH in the liver was measured immunohistochemically. The inductions of GST-P-positive foci in all DMH-treated groups were dose-dependent, duration-dependent and significantly higher than that in non-DMH-treated group. From these results, our assay model was detected the initiation activity of DMH simply, and would be useful to evaluate the carcinogenicity of chemicals.


Adoptive immunotherapy of a newly induced sarcoma: immunologic characteristics of effector cells.
A newly induced syngeneic transplantable sarcoma, MCA 105, was used for studies of the biologic characteristics of fresh noncultured and secondarily in vitro sensitized (IVS) cells with antitumor reactivity. Fresh spleen cells harvested from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum exhibited no detectable cytotoxic activity to MCA 105 tumor targets in a 4-hr chromium-release assay, and adoptive transfer of these cells mediated the specific regression of established MCA 105 tumors. Phenotypic analysis of fresh, noncultured immune cells revealed that the therapeutically effective cells expressed both the Lyt-1 and the Lyt-2 T cell differentiation antigens. The therapeutic efficacy of fresh noncultured immune cells was not augmented by the concomitant administration of exogeneous interleukin 2 (IL 2). Secondary IVS of fresh immune cells with irradiated MCA 105 tumor stimulator cells resulted in the generation of tumor-specific cytotoxic effector cells. The generation of cytotoxic effector cells required Lyt-1+, 2+ cytotoxic precursor cells. Effective adoptive immunotherapy with these IVS immune cells, unlike fresh noncultured immune cells, depended on the concomitant administration of IL 2. Furthermore, the generation of therapeutically effective cells did not require the specific stimulation by MCA 105 tumor cells, because cultures of MCA 105 immune spleen cells with FBL-3 lymphoma cells in vitro also contained in vivo functional immune effector cells. These cells, however, possessed no detectable MCA 105 cytotoxic activity in vitro. Although this observation suggests that a noncytotoxic cell population is sufficient to initiate tumor regression in vivo, it does not exclude the possibility that cytolytic cells are generated in vivo after adoptive transfer of these cells. As a whole, our results indicate that secondary IVS functional immune effector cells are characteristically distinct from freshly harvested immune cells.


A Tale of Two Teaching Methods: Students' Clinical Perspectives on Administering Dental Local Anesthetics.
Various preclinical methodologies have been adopted by dental and oral health programs to develop student competence in administering dental local anesthetics (LA). Student-to-student practice is the most common preclinical training method. However, manikin simulation models have been introduced to avoid possible complications and ethical concerns with student-to-student injections. In 2017, the methodology was changed in the Bachelor of Oral Health program at The University of Sydney School of Dentistry in Australia from student-to-student practice to manikin simulation models. The aim of this study was to compare the students' learning experience, perceived confidence, and anxiety in giving their first injections to patients in these two preclinical training methods. A mixed-methods cohort design was used to compare the 2016 (n = 42) and 2017 (n = 32) oral health students' experiences and perceptions and evaluate students' clinical experience after commencing LA practice on patients. Students completed a questionnaire about their perceived level of confidence and anxiety before and after their first LA to a child and an adult for both infiltration and inferior alveolar nerve b lock (IANB) injections. Focus groups were conducted to further investigate the students' experience. The results showed that the perceived confidence and anxiety of the two cohorts did not differ significantly from each other. Although students found it difficult to transition into clinical practice without having experienced LA themselves, the manikin simulation practice provided a safe learning platform that avoided ethical and legal concerns. These findings support the use of manikin simulation models as an alte rnative method for dental local anesthetic preclinical training.


Genomic and phenotypic characterization of Borrelia afzelii BO23 and Borrelia garinii CIP 103362.
In recent years, the number of Lyme disease or borreliosis cases in Eurasia has been dramatically increasing. This tick-borne disease is caused by Borrelia burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, the main species found in North America, and B. afzelii and B. garinii, which are primarily responsible for the disease in Eurasia. Currently, research on Lyme disease has focused mainly on B. burgdorferi while B. afzelii and B. garinii, which cause disease with distinctly different symptoms, are less studied. The purpose of this study is to evaluate B. afzelii BO23 and B. garinii CIP 103362 as model organisms to study Eurasian Lyme disease. To begin our analyses, we sequenced, annotated the chromosomes of both species and compared them to B. burgdorferi strain B31. We also assayed shuttle vector, pBSV2, for transformation efficacy and demonstrated that these strains can be cultured on solid media. In addition, we characterized how physicochemical parameters (e.g., oxygen, osmolarity, oxidative stress) affect both growth and motility of the bacteria. Finally, we describe each strain's antibiotic susceptibility and accessed their ability to infect mice. In conclusion, B. afzelii BO23 was more practical for in vitro and in vivo studies than B. garinii CIP 103362.


Asymptomatic microscopic hematuria.
To examine the 2001 American Urological Association (AUA) recommendations for the evaluation of asymptomatic microscopic hematuria (AMH) in light of the most recent studies available. AMH is a nonspecific marker of disease, but can also be found in healthy individuals. The research done seeks to better identify those patients who present with AMH and have a clinically significant disease. These investigations include epidemiological studies that describe populations at risk, define clinically significant hematuria, and provide long-term follow-up to patients with AMH. Authors have examined the validity and effectiveness of recommended and nonrecommended tests for AMH in different populations. Finally, several studies looked into what workup, if any, patients with AMH were receiving in the community. The evaluation of female patients with AMH needs to be tailored to the individual patient's presentation and risk factors. This evaluation should be timely and always include testing of both upper and lower urinary tract. After a complete negative assessment, no further follow-up is needed.


The cyclin-dependent kinase inhibitor butyrolactone is a potent inhibitor of p21 (WAF1/CIP1 expression).
Butyrolactone I (BL) is a competitive inhibitor of ATP for binding and activation of cyclin-dependent kinases and is a potent inhibitor of cell cycle progression. Treatment of H460 human lung and SW480 human colon cancer cells with doses of BL that exceed the Ki for CDK inhibition but which are much lower than doses required to inhibit MAPK, PKA, PKC, or EGFR lead to a rapid significant reduction of endogenous p21 protein expression. BL-dependent inhibition of p21 expression appears to be p53-independent. BL-dependent p21 degradation was blocked by lactacystin, consistent with the hypothesis that there is accelerated p21 proteasomal degradation in the presence of BL. BL also inhibited the p53-dependent increase of p21 protein expression in cells exposed to the DNA damag-ing agent etoposide, and favored a greater G2/M arrest as compared to the non-BL exposed cells. BL accelerated the degradation of exogenously expressed p21 that was not observed with a C-terminal truncated form of p21. Degradation of exogenous p21 led to a shift to G2 accumulation in the cells exposed to BL. We conclude that BL has effects on the cell cycle beyond its role as a CDK inhibitor and can be used as a novel tool to study the mechanism of p21 degradation and the consequences towards p21- dependent checkpoints.