[Brain death: attitude and knowledge of medical personnel in a third level hospital].
Brain death is defined as the irreversible loss of all functions of the brain, including the brainstem. The objective is to know the attitude and knowledge toward brain death of the medical personnel involved in the process of the organ/tissue transplantation and donation in a third level hospital of Mexico City. 67 attending physicians were interviewed with the methodology of pen, paper and a printed questionnaire. They were distributed in two groups: group A, consisting of non-surgical physicians, and group B, which was formed by surgical physicians. It was analyzed the attitude and knowledge of the criteria established in the Ley General de Salud (General Law of Health) of Mexico. Thirty-five men and 32 women (median age 42 years) responded to the survey. More than 90 % of both groups would wish to participate in a brain death course, and they would accept to be potential donors or receptors of transplanted organs. A high percentage knows partially the law on brain death (Ley General de Salud) and clinical procedures. Of the interviewed population, 68 % does not know the standard complementary studies to confirm the diagnosis of brain death. Non-significant differences were observed in the attitude and knowledge of both groups (p = 0.170). Physicians must improve their knowledge on brain death.


Bronchiolitis Obliterans and Primary Ciliary Dyskinesia: What Is the Link?
Bronchiolitis obliterans (BO) is a rare form of chronic obstructive lung disease characterized by obliteration of the small airways caused by inflammation and fibrosis. In children, BO most commonly appears following a severe lower respiratory tract infection. This phenomenon has been described as post-infectious BO (PIBO). PIBO presents with dyspnea, tachypnea, and persistent hypoxemia, as well as characteristic radiographic findings on high-resolution CT (HRCT) of the lungs. A few DNAH1 genetic variants have been postulated to have a role in the development of BO in patients with primary ciliary dyskinesia (PCD), but there is limited evidence regarding this, and etiologies are uncertain. PCD is a genetically heterogeneous autosomal recessive disorder characterized by ciliary dysfunction that causes impaired mucociliary clearance, leading to bronchiectasis and recurrent lower respiratory tract infections due to several pathogenic organisms including Pseudomonas aeruginosa. The link between rare PCD genetic variants and BO remains undetermined. We report the first case in Puerto Rico with Pseudomonal PIBO as the initial presentation of PCD; the patient was a four-year-old male. We also engage in a comparison of our case with previously reported cases of PIBO in PCD patients.


Unusual cystic presentation of pulmonary nodular amyloidosis associated with MALT-type lymphoma.
The case reported herein consists of nodular pulmonary amyloidosis presenting with unusual cystic radiological features which reveal a pulmonary localisation of an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). The present case is the first to report a radiological presentation of nodular pulmonary amyloidosis in the absence of Sjögren's syndrome. Although transthoracic fine-needle biopsy was helpful for the diagnostic of amyloidosis, final diagnosis of associated MALT-type lymphoma required an open lung biopsy. This emphasises the importance of performing surgical investigations in pulmonary nodular amyloidosis in order to depict the presence of underlying lung tumours or lymphoproliferative disorders.


Does it matter how coronary projections are combined to assess restenosis following PTCA?
Three methods were used to combine measurements from biplane coronary views to assess restenosis following PTCA. The first 153 patients from the EMPAR trial with 118 measurable coronary stenoses were chosen for this study. The mean difference between the RAO and LAO projections used was 88 +/- 22 degrees (S.D.). There was no systematic difference in coronary dimensions between RAO and LAO views for the group. Coronary restenosis was primarily defined as loss of 50% or more of the luminal diameter gain from the procedure. The ratio of luminal loss to gain was calculated for each stenosis using (Method 1) only the lesser diameter of the two views, (Method 2) an average of the two views and, (Method 3) a calculated cross-sectional coronary lumen area. Rates of restenosis calculated in this way ranged between 36 and 44% amongst the three methods, which was not significantly different. However, individual coronary lesions might be classified as either restenosed or not by this formula, depending on which method was used to integrate the biplane coronary measurements.


The visual P2 is attenuated for attended objects near the hands.
Vision is altered when people place their hands near the object they are observing. To investigate the neural processes underlying this effect, we measured electroencephalographic visual-evoked potentials (VEPs) elicited by reversing checkerboards, while participants' hands either surrounded the visual display or rested at their sides. We found the P2 component was attenuated for hand-proximal stimuli, but only when participants attended to the location of the checkerboard. In Experiment 1, participants performed an attention-demanding color-change task that was presented centrally, and the P2 component was attenuated for central, but not peripheral, checkerboards. In Experiment 2, participants performed the attention task in the periphery, and the P2 was attenuated for peripheral, but not central, checkerboards. These results suggest that hand-proximal stimuli benefit from enhanced selective attention at later stages of perceptual processing. The effect only occurs for objects at task-relevant locations, however, even when task-irrelevant locations are physically closer to the hands.


Evidence for Two Photoreactions and Possible Involvement of Phytochrome in Light-dependent Stomatal Opening.
Leaves of the xantha mutant of Helianthus annuus have a higher rate of transpiration and a lower diffusive resistance in the light than in the dark. Stomates of this nonphotosynthetic mutant open in the light and close in the dark.Comparative studies of tobacco, xantha mutant, and wild-type sunflower stomatal opening over a range of light intensities in isolated portions of the spectrum reveal two patterns of response: (a) a low intensity opening in the green and far red characterized by partial opening, absence of a threshold, and saturation of the response at low light intensities; (b) a high intensity response in the blue characterized by a threshold (intensities greater than 100 microwatts per square centimeter needed for opening) and a linear opening response at higher incident light intensities. In xantha mutant stomates only the low intensity system appears to be operational, while both low and high intensity systems are present in the wild-type sunflower and tobacco.Red light has an inhibiting effect on stomatal opening in both mutant and wild-type sunflowers. They require prior exposure to far red for opening to occur in red light. This redfar red antagonism suggests the involvement of phytochrome.


[Total hip and knee arthroplasty for arthropathy in a hemophiliac].
We evaluated the medium-term follow-up results, effectiveness, and suitability of arthroplasty for hemophilic arthropathy. We performed 26 total knee and 9 total hip arthroplasty operations on hemophilic patients between 1988 and 1998 under general anesthesia and appropriate hemostatic management. Postoperative treatment for hemophilic arthropathy is the same as that for osteoarthritis and rheumatoid arthritis. After their operations, patients experienced relief from pain and intra-articular bleeding in affected joints but only marginal improvement in the range of motion. In general, total joint arthroplasty is not indicated for young patients. However, arthropathy can have a severe impact on the active life of patients during their youth. For severe hemophilic arthritis, total knee and hip arthroplasty can lead to a pain-free and improved quality of life. We believe total knee and hip arthroplasty is a good solutions for hemophiliac arthropathy before severe deformity occurs. Although treated relatively young hemophilic patients, age was not considered to be a contraindication.


Geometrical optics in thin film light guides.
We consider thin film light guides consisting of a transparent film of high refractive index deposited on a substrate of lower index. The propagation of light in such a two-dimensional transmission medium can be described within the limits of geometrical optics by an effective index of refraction N. Its value depends on the film thickness. Therefore, a light beam in the thin film guide is refracted or totally reflected at a step of film thickness. We discuss these phenomena (Snell's law) and demonstrate them experimentally, using ZnS films on glass as guides. As applications, we show a thin film prism and thin film lenses for guided light beams. By properly choosing the film thicknesses at both sides of the step, one can obtain an unusually large positive or negative wavelength dispersion of the refraction or, if desired, achromatic refraction.


Duplex Ultrasound versus Computed Tomography for the Postoperative Follow-Up of Endovascular Abdominal Aortic Aneurysm Repair. Where Do We Stand Now?
In the last decade, endovascular aneurysm repair (EVAR) has rapidly developed to be the preferred method for infrarenal abdominal aortic aneurysm repair in patients with suitable anatomy. EVAR offers the advantage of lower perioperative mortality and morbidity but carries the cost of device-related complications such as endoleak, graft migration, graft thrombosis, and structural graft failure. These complications mandate a lifelong surveillance of EVAR patients and their endografts. The purpose of this study is to review and evaluate the safety of color-duplex ultrasound (CDU) as compared with computed tomography (CT), based on the current literature, for post-EVAR surveillance. The post-EVAR follow-up modalities, CDU versus CT, are evaluated questioning three parameters: (1) accuracy of aneurysm size, (2) detection and classification of endoleaks, and (3) detection of stent-graft deformation. Studies comparing CDU with CT scan for investigation of post-EVAR complications have produced mixed results. Further and long-term research is needed to evaluate the efficacy of CDU versus CT, before CDU can be recommended as the primary imaging modality for EVAR surveillance, in place of CT for stable aneurysms.


Role of serology in the diagnosis of toxoplasmic lymphadenopathy.
Serologic results obtained in 92 cases of toxoplasmic lymphadenopathy diagnosed by lymph node biopsy were reviewed, and guidelines for serologic diagnosis of this disease were established. When tests were first performed within six months of onset of lymphadenopathy, single high titers of IgG toxoplasma antibodies (suggestive of acute infection) were found with the Sabin-Feldman dye test and the direct agglutination test in 93% and 76% of cases, respectively. Observations of significant rises in titer were uncommon because of the late acquisition of sera. Within the first six months after the onset of lymphadenopathy, IgM toxoplasma antibody was demonstrable by the double-sandwich IgM enzyme-linked immunosorbent assay in 88% of cases and by the IgM-immunofluorescent antibody test in 78%. Twenty percent of patients who had serum samples drawn more than 12 months after onset lymphadenopathy still had IgM toxoplasma antibodies demonstrable by the enzyme-linked immunosorbent assay. No patient first tested six or more months after onset of lymphadenopathy was positive in the IgM-immunofluorescent antibody test. These results provide the basis for recommendations on the use of serologic tests for the diagnosis of acute toxoplasmic lymphadenopathy.


Genetic polymorphism of haptoglobin subtypes in a Japanese population.
Haptoglobin (Hp) subtypes have been determined in the Japanese population by polyacrylamide gel isoelectric focusing followed by immunoblotting and by two-dimensional polyacrylamide gel electrophoresis. In the present study, neuraminidase-treated plasma samples were used for subtyping of Hp, without prior purification. These samples were obtained from 372 unrelated healthy donors. Allelic frequencies were: Hp*1F = 0.0014; Hp*1S+ = 0.2688; Hp*2FF = 0.0000; Hp*2FS = 0.7284, and Hp*2SS = 0.0014. The phenotypic distribution was in good accordance with the Hardy-Weinberg equilibrium.


Partitional calorimetry.
For thermal physiologists, calorimetry is an important methodological tool to assess human heat balance during heat or cold exposures. A whole body direct calorimeter remains the gold standard instrument for assessing human heat balance; however, this equipment is rarely available to most researchers. A more widely accessible substitute is partitional calorimetry, a method by which all components of the conceptual heat balance equation-metabolic heat production, conduction, radiation, convection, and evaporation-are calculated separately based on fundamental properties of energy exchange. Since partitional calorimetry requires relatively inexpensive equipment (vs. direct calorimetry) and can be used over a wider range of experimental conditions (i.e., different physical activities, laboratory or field settings, clothed or seminude), it allows investigators to address a wide range of problems such as predicting human responses to thermal stress, developing climatic exposure limits and fluid replacement guidelines, estimating clothing properties, evaluating cooling/warming interventions, and identifying potential thermoregulatory dysfunction in unique populations. In this Cores of Reproducibility in Physiology (CORP) review, we summarize the fundamental principles underlying the use of partitional calorimetry, present the various methodological and arithmetic requirements, and provide typical examples of its use. Strategies to minimize estimation error of specific heat balance components, as well as the limitations of the method, are also discussed. The goal of this CORP paper is to present a standardized methodology and thus improve the accuracy and reproducibility of research employing partitional calorimetry.


N-Spirocyclic Quaternary Ammonium Ionenes for Anion-Exchange Membranes.
The development of cationic polymers for anion-exchange membranes (AEMs) with high alkaline stability and conductivity is a considerable challenge in materials chemistry. In response, we here present the synthesis and properties of N-spirocyclic quaternary ammonium ionenes (spiro-ionenes) containing 5- and 6-membered rings fused by central nitrogen cations. High-molecular weight and film-forming spiro-ionenes are successfully synthesized in cyclo-polycondensations of tetrakis(bromomethyl)benzene and dipiperidines under mild conditions. These polyelectrolytes show excellent thermal and alkaline stability with no degradation detected by NMR spectroscopy after more than 1800 h in 1 M KOD/D2O at 80 °C. Even at 120 °C, the spiro-ionenes display reasonable alkaline stability. Transparent and mechanically robust AEMs based on ionically cross-linked blends of spiro-ionene and polybenzimidazole reach OH- conductivities up to 0.12 S cm-1 at 90 °C. The current findings demonstrate that spiro-ionenes constitute a new class of alkali-stable anion-exchange polymers and membranes.


Exploring the Feasibility of Pipeline Embolization Device Compared With Stent-Assisted Coiling to Treat Non-saccular, Unruptured, Intradural Vertebral Artery Aneurysms.
Object: The pipeline embolization device (PED) has been used to treat non-saccular, unruptured, intradural vertebral artery aneurysms at some institutions. However, there is an absence of large controlled studies validating the feasibility of this treatment. This study aimed to explore the therapeutic feasibility of PED by comparing PED treatment with controlled stent-assisted coiling (SAC). Materials and Methods: Thirty-two PED procedures were matched in a 1:2 manner with 64 SAC procedures based on patient age, sex, aneurysm size, and aneurysm location. Technical factors, procedural complications, angiographic results, and clinical outcomes were analyzed and compared. Results: There was no statistically significant difference in technical factors and procedural complications between the two groups (PED vs. SAC, 9.4 vs. 4.7%, P = 0.397). In multivariate analysis, smoking and therapeutic modality were identified as independent predictors of occlusion. Smoking was a risk factor for aneurysm obliteration [hazard ratio (HR) 0.53; 95% confidence interval (CI), 0.31-0.89; P = 0.018]. Aneurysms treated with PED were more likely to achieve obliteration over time compared with aneurysms treated with SAC (HR 2.97; 95% CI, 1.79-4.93; P < 0.001). The rate of favorable clinical outcomes (modified Rankin Scale (mRS), 0-2) was similar between the two groups (PED vs. SAC, 100 vs. 96.9%, P = 0.551). In the SAC group, one patient had neurological deficit with an mRS of four at the latest follow-up. There was no mortality in either group. Conclusions: The PED and SAC groups showed similar technical factors, procedural complications, angiographic results, and favorable clinical outcomes. Aneurysms treated with PED were more prone to obliteration over time than aneurysms treated with SAC. These outcomes suggest, based on short-term follow-up, PED is a safe and feasible strategy for the treatment of non-saccular, unruptured, intradural vertebral artery aneurysms.


Heat Shock-Binding Protein 21 Regulates the Innate Immune Response to Viral Infection.
The induction of interferons (IFNs) plays an important role in the elimination of invading pathogens. Heat shock binding protein 21 (HBP21), first known as a molecular chaperone of HSP70, is involved in tumor development. Heat shock binding proteins have been shown to regulate diverse biological processes, such as cell cycle, kinetochore localization, transcription, and cilium formation. Their role in antimicrobial immunity remains unknown. Here, we found that HBP21 drives a positive feedback loop to promote IRF3-mediated IFN production triggered by viral infection. HBP21 deficiency significantly impaired the virus-induced production of IFN and resulted in greater susceptibility to viral infection both in vitro and in vivo. Mechanistically, HBP21 interacted with IRF3 and promoted the formation of a TBK1-IRF3 complex. Moreover, HBP21 abolished the interaction between PP2A and IRF3 to repress the dephosphorylation of IRF3. Analysis of HBP21 protein structure further confirmed that HBP21 promotes the activation of IRF3 by depressing the dephosphorylation of IRF3 by PP2A. Further study demonstrated that virus-induced phosphorylation of Ser85 and Ser153 of HBP21 itself is important for the phosphorylation and dimerization of IRF3. Our study identifies HBP21 as a new positive regulator of innate antiviral response, which adds novel insight into activation of IRF3 controlled by multiple networks that specify behavior of tumors and immunity. IMPORTANCE The innate immune system is the first-line host defense against microbial pathogen invasion. The physiological functions of molecular chaperones, involving cell differentiation, migration, proliferation and inflammation, have been intensively studied. HBP21 as a molecular chaperone is critical for tumor development. Tumor is related to immunity. Whether HBP21 regulates immunity remains unknown. Here, we found that HBP21 promotes innate immunity response by dual regulation of IRF3. HBP21 interacts with IRF3 and promotes the formation of a TBK1-IRF3 complex. Moreover, HBP21 disturbs the interaction between PP2A and IRF3 to depress the dephosphorylation of IRF3. Analysis of HBP21 protein structure confirms that HBP21 promotes the activation of IRF3 by blocking the dephosphorylation of IRF3 by PP2A. Interestingly, virus-induced Ser85 and Ser153 phosphorylation of HBP21 is important for IRF3 activation. Our findings add to the known novel immunological functions of molecular chaperones and provide new insights into the regulation of innate immunity.


Chairside intraoral qualitative somatosensory testing: reliability and comparison between patients with atypical odontalgia and healthy controls.
To assess intraoral inter- and intraexaminer reliability of three qualitative measures of intraoral somatosensory function and to compare these measures between patients with atypical odontalgia (AO) and healthy controls. Thirty-one AO patients and 47 healthy controls participated. Inter- and intraexaminer reliability was tested on a subgroup of 46 subjects (25 AO; 21 healthy). Sensitivity to touch, cold, and pinprick stimuli was evaluated on the painful gingival site and the corresponding contralateral site in AO patients, and bilaterally on the gingiva of the first maxillary premolars in controls. Patients were asked to report hypersensitivity, hyposensitivity, or normal sensitivity to stimuli on the painful site compared with the nonpainful site. Kappa values were calculated, and chi-square and Fisher's exact tests were used to compare frequencies between groups. Kappa values ranged between 0.63 and 0.75. The frequency of hypersensitivity to either modality was significantly higher in patients (29% to 61%) than in controls (9% to 17%) (P < .015), whereas reports of hyposensitivity were similar between groups (2% to 16%) (P > .057). Only 3.2% of the AO patients had no reports of abnormal sensitivity on any of the tests, compared with 59.6% of the healthy subjects (P < .001). Intraoral qualitative somatosensory testing can detect intraoral sensory disturbances in AO patients, and the reliability is sufficient for initial screening of orofacial somatosensory function.


Application of capillary electrophoresis in clinical chemistry--developments from preliminary trials to routine analysis.
Since instruments performing capillary electrophoresis (CE) became commercially available in the late 1980s, information on this relatively new analytical technique has been increasing almost exponentially. At the beginning of the last decade, fundamental discoveries in the field were made mainly in the laboratories of analytical chemists; but now, this separation science is giving increasing impact to the laboratories of clinical chemists. This paper briefly reviews the history, instrumentation, different modes and theory of CE, and the prominent fields of its applications in clinical chemistry.


Parallel Mechanism Composed of Abdominal Cuticles and Muscles Simulates the Complex and Diverse Movements of Honey Bee (Apis mellifera L.) Abdomen.
The abdominal intersegmental structures allow insects, such as honey bees, dragonflies, butterflies, and drosophilae, to complete diverse behavioral movements. In order to reveal how the complex abdominal movements of these insects are produced, we use the honey bee (Apis mellifera L.) as a typical insect to study the relationship between intersegmental structures and abdominal motions. Microstructure observational experiments are performed by using the stereoscope and the scanning electron microscope. We find that a parallel mechanism, composed of abdominal cuticle and muscles between the adjacent segments, produces the complex and diverse movements of the honey bee abdomen. These properties regulate multiple behavioral activities such as waggle dance and flight attitude adjustment. The experimental results demonstrate that it is the joint efforts of the muscles and membranes that connected the adjacent cuticles together. The honey bee abdomen can be waggled, expanded, contracted, and flexed with the actions of the muscles. From the view point of mechanics, a parallel mechanism is evolved from the intersegmental connection structures of the honey bee abdomen. Here, we conduct a kinematic analysis of the parallel mechanism to simulate the intersegmental abdominal motions.


Computed tomographic angiography in planning abdomen-based microsurgical breast reconstruction: a comparison with color duplex ultrasound.
To plan abdominal perforator-based microsurgical breast reconstruction, duplex ultrasound is often employed to preoperatively identify the location of abdominal wall perforating vessels. Recently, several groups have published the use of computed tomography angiography for preoperative planning in perforator flap breast reconstruction. The purpose of this study was to compare the accuracy of computed tomography angiography in locating clinically useful abdominal wall perforators with that of duplex ultrasound. A prospective study was conducted of 22 consecutive patients undergoing 30 abdomen-based microsurgical breast reconstructions using both preoperative computed tomography angiography and duplex ultrasound. Perforator data were obtained with both computed tomography angiography and ultrasound. The two largest perforators were chosen per abdominal side for comparison between studies. In addition, the locations of perforators were confirmed at surgery. Computed tomography angiography preoperatively identified 83 of the largest perforators, while only 55 of these large perforators (66.3 percent) were preoperatively identified on ultrasound. No superficial inferior epigastric arteries were identified by ultrasound. However, in all eight breast reconstructions performed with the superficial inferior epigastric system, the superficial inferior epigastric arteries were identified preoperatively as adequate size for microsurgical transfers, with an average diameter of 1.6 mm. There are many advantages to preoperative computed tomography angiography for planning abdominal perforator-based microsurgical breast reconstruction, including accurate identification of perforating vessels, the underlying branching pattern of the deep inferior epigastric artery, and the presence of the superficial inferior epigastric vessels. This study demonstrates the superiority of computed tomography angiography over duplex ultrasound as a tool for preoperative planning of perforator-based breast reconstruction.


Quantifying the aesthetic outcomes of breast cancer treatment: assessment of artificial scars.
All breast cancer treatment involves surgery, which inevitably leaves scars. Some previous studies of scarring in other healthcare settings have employed colorimeters. However, specialized colorimetry equipment is not widely used in plastic surgery; Instead, surgical outcomes are documented using digital photography. In this study, we used controlled experiments with artificial scars to compare measurements obtained by a colorimeter and a digital camera.


[Study on dietary pattern and nutrients intakes of residents in areas of high and low incidence of esophageal cancer].
The dietary pattern and nutrients intakes of residents in areas with high and low prevalence of esophageal cancer were studied by 3 days' dietary survey. The results showed that the dietary pattern and nutrients intakes of residents in areas with low prevalence (ALP) of esophageal cancer was superior to that in area with high prevalence (AHP). The amount of soybean, meat and vegetable consumed by residents in the ALP was more than that in the AHP. Deep color vegetable and gaelic vegetable were dominant in ALP, but so were light color vegetables in AHP. The protein quality and quantity as well as the amount of Zn, Ca, RE and riboflavin consumed in the AHP were lower than that in the ALP. The energy from carbohydrate accounts for 78.14% of the total in the AHP. It is suggested that poor dietary pattern and the quality and amount of nutrients intake may be related to the development of esophageal cancer, and nutrition intervention in area of high prevalence seems rational.


Structural and Functional Brain Abnormalities in Internet Gaming Disorder and Attention-Deficit/Hyperactivity Disorder: A Comparative Meta-Analysis.
Background: Patients with Internet gaming disorder (IGD) and attention-deficit/hyperactivity disorder (ADHD) have high comorbidity but it is still unknown whether these disorders have shared and distinctive neuroimage alterations. Objective: The aim of this meta-analysis was to identify shared and disorder-specific structural, functional, and multimodal abnormalities between IGD and ADHD. Methods: A systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies comparing people with IGD or ADHD with healthy controls. Regional gray matter volume (GMV) and fMRI differences were compared over the patient groups and then a quantitative comparison was performed to find abnormalities (relative to controls) between IGD and ADHD using seed-based d mapping meta-analytic methods. Result: The meta-analysis contained 14 IGD VBM studies (contrasts covering 333 IGDs and 335 HCs), 26 ADHD VBM studies (1,051 patients with ADHD and 887 controls), 30 IGD fMRI studies (603 patients with IGD and 564 controls), and 29 ADHD fMRI studies (878 patients with ADHD and 803 controls). Structurally, VBM analysis showed disorder-specific GMV abnormality in the putamen among IGD subjects and orbitofrontal cortex in ADHD and shared GMV in the prefrontal cortex. Functionally, fMRI analysis discovered that IGD-differentiating increased activation in the precuneus and shared abnormal activation in anterior cingulate cortex, insular, and striatum. Conclusion: IGD and ADHD have shared and special structural and functional alterations. IGD has disorder-differentiating structural alterations in the putamen and ADHD has alterations in the orbitofrontal cortex. Disorder-differentiating fMRI activations were predominantly observed in the precuneus among IGD subjects and shared impairing function connection was in the rewards circuit (including ACC, OFC, and striatum).


Recruitment of mammalian cell fibronectin to the surface of Chlamydia trachomatis.
Pathogenic bacteria exploit the presence of various host cell molecules in order to colonize new tissues. Fibronectin is involved in a wide range of cell functions in vivo, and staphylococci, streptococci, and gonococci have evolved mechanisms to utilize this glycoprotein to mediate host cell binding. We show that elementary bodies (EB) from two biovars of Chlamydia trachomatis recruit fibronectin to their surfaces upon lysis of the host cell. We also demonstrate that a heparan sulfate lyase-sensitive molecule on chlamydial EB is responsible for binding at least a portion of this fibronectin.


Song Morphing by Humpback Whales: Cultural or Epiphenomenal?
Singing humpback whales (Megaptera noavaengliae) collectively and progressively change the sounds and patterns they produce within their songs throughout their lives. The dynamic modifications that humpback whales make to their songs are often cited as an impressive example of cultural transmission through vocal learning in a non-human. Some elements of song change challenge this interpretation, however, including: (1) singers often incrementally and progressively morph phrases within and across songs as time passes, with trajectories of change being comparable across multiple time scales; (2) acoustically isolated subpopulations singing similar songs morph the acoustic properties of songs in similar ways; and (3) complex sound patterns, including phrases, themes, and whole songs, recur across years and populations. These properties of song dynamics suggest that singing humpback whales may be modulating song features in response to local conditions and genetic predispositions rather than socially learning novel sound patterns by copying other singers. Experimental and observational tests of key predictions of these alternative hypotheses are critical to identifying how and why singing humpback whales constantly change their songs.


Effect of occlusal restoration on stresses around class V restoration interface: a finite-element study.
Causes of failures in class V restorations have always been controversial until now, since the biomechanical aspects of these restorations have been understood. This study was aimed to verify the hypothesis that eccentric forces are the cause of cuspal flexure, which lead to excessive stresses at the periphery of a class V restoration, further it identifies the amount of the stress and the flexure increase in the presence of an occlusal restoration using different restorative materials to restore (both cervical and occlusal) along with their comparison with respect to amount of stresses around the cervical restorations. The study was done by modeling a mandibular first premolar which was sectioned bucco-lingually, in the NISA, EMRC II finite element software. A 100N eccentric load was applied on the tooth structure and stresses were observed at the peripheries of the class V restoration when it was restored with composite and with glass ionomer cement. The stresses were further analyzed in the presence of occlusal restorations with different materials and configurations. It was seen that the stresses at the gingival wall interface in case of class V glass ionomer cement was more than that for composite. In the presence of an occlusal amalgam restoration, the cuspal flexure was more than that of occlusal composite and the stresses at the class V peripheries were also statistically significant. It was suggested that lower modulus composites can flex with the tooth structure decreasing the bond failure and that the stresses are much lesser when there is absence of an occlusal restoration. Occlusal composite restorations reinforce the tooth structure and reduce the cuspal flexure as compared to silver amalgam.


Common aspects of human and primate seronegative arthritis.
A 27-year-old female lowland gorilla developed an asymmetric oligoarthritis 3 months post-partum. There was no evidence of an antecedent gastrointestinal or genitourinary infection. Serum was negative for rheumatoid factor and antinuclear antibody. Synovial fluid revealed 2000 white blood cells with negative cultures and polarized microscopy. Studies on synoviocytes were the following: (1) FACS analysis revealed surface expression of a B27-like epitope of the cells. (2) Analysis of intracellular clearance kinetics of arthritogenic organisms showed peak intracellular colony-forming units at 48 hours after bacterial invasion, and clearance by 13 days post-invasion. (3) Interferon-y (0.1-10.0 ng/ml)accelerated intracellular microbicidal pathways in a dose-dependent fashion. These findings closely parallel those seen in human synoviocytes of patients with spondyloarthropathy. Primate and human seronegative arthritis share clinical and immunologic features, as well as aspects of host:pathogen defense mechanisms. The interplay of genetic and microbial factors underlying this arthritis appears to be conserved across these species boundaries.


Three dimensional image restoration in fluorescence lifetime imaging microscopy.
A microscope set-up and numerical methods are described which enable the measurement and reconstruction of three-dimensional nanosecond fluorescence lifetime images in every voxel. The frequency domain fluorescence lifetime imaging microscope (FLIM) utilizes phase detection of high-frequency modulated light by homodyne mixing on a microchannel plate image intensifier. The output signal at the image intensifier's phosphor screen is integrated on a charge coupled device camera. A scanning stage is employed to obtain a series of phase-dependent intensity images at equally separated depths in a specimen. The Fourier transform of phase-dependent data gives three-dimensional (3D) images of the Fourier coefficients. These images are deblurred using an Iterative Constrained Tikhonov-Miller (ICTM) algorithm in conjunction with a measured point spread function. The 3D reconstruction of fluorescence lifetimes are calculated from the deblurred images of the Fourier coefficients. An improved spatial and temporal resolution of fluorescence lifetimes was obtained using this approach to the reconstruction of simulated 3D FLIM data. The technique was applied to restore 3D FLIM data of a live cell specimen expressing two green fluorescent protein fusion constructs having distinct fluorescence lifetimes which localized to separate cellular compartments.


Molecular epidemiology of hepatitis E virus in Hong Kong.
Hepatitis E virus (HEV) is one of the major causes of acute and self-limiting hepatitis in human. In Hong Kong, the number of notifications increased from 26 to 62 from year 2001 to 2007. This study describes the molecular epidemiology of HEV in Hong Kong in order to determine the movement and distribution of HEV. HEV in 171 serum samples from HEV IgM positive cases from year 2001 to 2007 were amplified using RT-PCR and subjected to nucleotide sequencing. Phylogenetic analysis showed 162 of 171 HEV detected cases (94.7%) belonged to genotype IV and 8 (4.7%) to genotype I. Interestingly, a cluster of 10 cases in year 2007 that had the same sequence of HEV was identified. Epidemiological data however did not detect any relationship between these cases. Since zoonotic transmission is a well known route of HEV infection, close monitoring of the circulating HEV strains in human and food source animals may help to provide additional information on the transmission of HEV and possible source of infection in Hong Kong.


Application and potential of capillary electroseparation methods to determine antioxidant phenolic compounds from plant food material.
Antioxidants are one of the most common active ingredients of nutritionally functional foods which can play an important role in the prevention of oxidation and cellular damage inhibiting or delaying the oxidative processes. In recent years there has been an increased interest in the application of antioxidants to medical treatment as information is constantly gathered linking the development of human diseases to oxidative stress. Within antioxidants, phenolic molecules are an important category of compounds, commonly present in a wide variety of plant food materials. Their correct determination is pivotal nowadays and involves their extraction from the sample, analytical separation, identification, quantification and interpretation of the data. The aim of this review is to provide an overview about all the necessary steps of any analytical procedure to achieve the determination of phenolic compounds from plant matrices, paying particular attention to the application and potential of capillary electroseparation methods. Since it is quite complicated to establish a classification of plant food material, and to structure the current review, we will group the different matrices as follows: fruits, vegetables, herbs, spices and medicinal plants, beverages, vegetable oils, cereals, legumes and nuts and other matrices (including cocoa beans and bee products). At the end of the overview, we include two sections to explain the usefulness of the data about phenols provided by capillary electrophoresis and the newest trends.


Structural characterisation of degradation products formed upon di-n-butyl phthalate radiolysis by high-performance liquid chromatography electrospray tandem mass spectrometry.
Structural characterisation of 15 degradation products, formed upon di-n-butyl phthalate (DBP) radiolysis, has been achieved using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) coupling. The dissociation behaviour of protonated DBP was first established to be further used to characterise structural deviation in the degradation products. Based on accurate mass measurements, compounds shown by HPLC-MS analysis were all found to be DBP oxidation products, amongst which various sets of isomers could be distinguished. Collision-induced dissociation experiments performed on each electrosprayed molecule first allowed unambiguous definition of the location of the additional oxygen atoms; that is, in the alkyl branch or on the aromatic ring. Although location of the oxygen atom in the alkyl branches could not always be precisely determined, relative abundances of some product ions allowed oxygenated functions to be identified.


Suppression of ventilation artifacts for gastrointestinal slow wave recordings.
Gastrointestinal extracellular slow wave recordings are providing critical information about normal motility and pathophysiology of the gut. Processing the signals is an important adjunct to acquire clinically and physiologically meaningful analysis. In stomach and intestine in vivo slow wave recordings, ventilation (or respiratory) artifacts can be prominent, which hinders identification and analysis of slow wave profiles. Here, we introduce an algorithm to suppress these artifacts without distorting the slow wave morphology. The algorithm generates a cycle averaged ventilation signal by shifting the raw signal by its ventilation period. The cycle averaged ventilation signal is then subtracted from the slow wave recording. The algorithm was validated using signal to noise ratio (SNR) and Pearson correlation coefficient (PCC) on synthetic signals and SNR with experimental recordings. With synthetic data, SNR and PCC, improved by 7.29±1.14 dB and 0.23±0.15.With experimental data SNR improved by 2.66±0.60 dB. This method improves the slow wave signal content revealing a more accurate estimate of the slow wave morphology. The application of this method will lead to improved analysis of slow wave recordings to understand gut function.


Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats.
Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase receptor MerTK is a major player in the phagocytosis process. Experimental models of renal I/R events are of major importance for identifying I/R key players and for elaborating novel therapeutical approaches. A major aim of our study was to investigate possible involvement of MerTK in renal I/R. We performed our study on both natural mutant rats for MerTK (referred to as RCS) and on wild type rats referred to as WT. I/R was established by of bilateral clamping of the renal pedicles for 30' followed by three days of reperfusion. Plasma samples were analysed for creatinine, aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), kidney injury molecule -1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels and for MPs. Kidney tissue damage and CD68-positive cell requirement were analysed by histochemistry. monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and histone 3A (H3A) levels in kidney tissue lysates were analysed by western blotting. The phagocytic activity of blood-isolated monocytes collected from RCS or WT towards annexin-V positive bodies derived from cultured renal cell was assessed by fluorescence-activated single cell sorting (FACS) and confocal microscopy analyses. The renal I/R model for RCS rat described for the first time here paves the way for further investigations of MerTK-dependent events in renal tissue injury and repair mechanisms.


Origins and Function of VL30 lncRNA Packaging in Small Extracellular Vesicles: Implications for Cellular Physiology and Pathology.
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease.


[Epidemiological studies on legionella infection in Taiyuan area of Shanxi Province].
To study the prevalence and epidemic features of legionella infection in Taiyuan area of Shanxi Province. IgM and IgG antibodies against 15 types of nine species of legionella were determined with enzyme-linked immunosorbent assay for out-patients, in-patients and healthy population. Positive IgM to legionella accounted for 17.4% in adult patients and 13.2% in child patients, with the highest infection rate both in the adults and children with acute respiratory infection and prevalent in the summer. The peak age of infection was at 30 to 50 years old for adults. Incidence of acute legionella infection in children increased with age. Acute infection occurred in six patients two weeks after their hospitalization with positive IgM against legionella. In healthy population, infection rate was the highest in employees of coal mines (36.7%) and the lowest in urban children (9.5%). Legionella micdadei and legionella pneumophila were the two most common causes of infection in adults and children patients and Legionella pneumophila in healthy population. Legionella are common pathogen of infections, possible to cause nosocomial infection. Legionella infection is also common in healthy population, especially in those often exposed occupationally to water and soil.


Qualitative review on N-methyl-D-aspartate receptor expression in rat spinal cord during the postnatal development: Implications for central sensitization and pain.
The N-methyl-D-aspartate receptor (NMDAR) is an important mediator of central sensitization and nociception in the rat spinal dorsal horn. The NMDAR subunits and splice variants determine the properties of the receptor. Understanding the expression of NMDAR subunits in spinal cord during the neonatal development is important as it may have consequences for the process of central sensitization and nociception in later life. In this review, a systematic literature search was conducted using three databases: Medline, Embase, and PubMed. A quality assessment was performed on predetermined entities of bias. Thirteen articles were identified to be relevant. The results show that NMDAR subunits and splice variants are dynamically expressed during postnatal development in the spinal dorsal horn. During the first 2 weeks, the expression of less excitable GluN2A subunit and more sensitive GluN2B subunit increases while the expression of high excitable GluN2C subunit decreases. During the 2nd week of postnatal development GluN1 subunits with exon 21 spliced in but exon 22 spliced out are predominantly expressed, increasing phosphorylation, and transport to the membrane. The data suggest that in rats, the nociceptive system is most susceptible to central sensitization processes during the first two postnatal weeks. This may have important consequences for nociception and pain responses in later life. From this, we conclude that targeted therapy directed toward specific NMDAR subunits is a promising candidate for mechanism-based treatment of pain in neonates.


Repeatability of short-duration transient visual evoked potentials in normal subjects.
To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1-2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant System (Diopsys, Inc., Pine Brook, New Jersey, USA). A checkerboard stimulus was modulated at two reversals per second. Two different contrasts of checkerboard reversal patterns were used: 85% Michelson contrast with a mean luminance of 66.25 cd/m(2) and 10% Michelson contrast with a mean luminance of 112 cd/m(2). Each test lasted 20 s. Both eyes, independently and together, were tested 10 times (5 times at each contrast level). The following information was identified from the filtered N75-P100-N135 complex: N75 amplitude, N75 latency, P100 amplitude, P100 latency, and Delta Amplitude (N75-P100). The median values for each eye's five SD-tVEP parameters were calculated and grouped into two data sets based on contrast level. Mean age was 27.3 +/- 5.2 years. For OD only, the median (95% confidence intervals) of Delta Amplitude (N75-P100) amplitudes at 10% and 85% contrast were 4.6 uV (4.1-5.9) and 7.1 uV (5.15-9.31). The median P100 latencies were 115.2 ms (112.0-117.7) and 104.0 ms (99.9-106.0). There was little within-session variability for any of these parameters. Intraclass correlation coefficients ranged between 0.64 and 0.98, and within subject coefficients of variation were 3-5% (P100 latency) and 15-30% (Delta Amplitude (N75-P100) amplitude). Bland-Altman plots showed good agreement between the first and fifth test sessions (85% contrast Delta Amplitude (N75-P100) delta amplitude, mean difference, 0.48 mV, 95% CI, -0.18-1.12; 85% contrast P100 latency delay, -0.82 ms, 95% CI, -3.12-1.46; 10% contrast Delta Amplitude (N75-P100) amplitude, 0.58 mV, 95% CI, -0.27-1.45; 10% contrast P100 latency delay, -2.05 mV, 95% CI, -5.12-1.01). The inter-eye correlation and agreement were significant for both SD-tVEP amplitude and P100 latency measurements. For the subset of eyes in which the inter-session repeatability was tested, the intraclass correlation coefficients ranged between 0.71 and 0.86 with good agreement shown on Bland-Altman plots. Short-duration transient VEP technology showed good within-session, inter-session repeatability, and good inter-eye correlation and agreement.


Optimal classes of chemotherapeutic agents sensitized by specific small-molecule inhibitors of akt in vitro and in vivo.
Akt is a serine/threonine kinase that transduces survival signals from survival/growth factors. Deregulation and signal imbalance in cancer cells make them prone to apoptosis. Upregulation or activation of Akt to aid the survival of cancer cells is a common theme in human malignancies. We have developed small-molecule Akt inhibitors that are potent and specific. These Akt inhibitors can inhibit Akt activity and block phosphorylation by Akt on multiple downstream targets in cells. Synergy in apoptosis induction was observed when Akt inhibitors were combined with doxorubicin or camptothecin. Akt inhibitor-induced enhancement of topoisomerase inhibitor cytotoxicity was also evident in long-term cell survival assay. Synergy with paclitaxel in apoptosis induction was evident in cells pretreated with paclitaxel, and enhancement of tumor delay by paclitaxel was demonstrated through cotreatment with Akt inhibitor Compound A (A-443654). Combination with other classes of chemotherapeutic agents did not yield any enhancement of cytotoxicity. These findings provide important guidance in selecting appropriate classes of chemotherapeutic agents for combination with Akt inhibitors in cancer treatment.


Treatment of advanced thymoma and thymic carcinoma.
Although thymic epithelial tumors are rare, they are relatively common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrounding structures and metastasize to distant sites. Thymic carcinomas are rare, but are highly aggressive tumors that are associated with a poor prognosis. The mainstay of therapy is complete surgical resection. Locally advanced thymoma and thymic carcinoma require a multimodality treatment approach with a combination of surgery, chemotherapy, and radiation therapy to decrease the chances of recurrence and improve survival. The risk of disease recurrence lasts for a number of years after completion of primary therapy. A majority of cases of recurrent disease present as pleural recurrences. Once again, surgical resection of recurrent disease represents the cornerstone of successful therapy and is critical to long-term survival. In recent years, a better understanding of the biologic basis of thymic epithelial tumors has led to the emergence of targeted therapy directed against this malignancy.


Effects of Equine-Assistant Activity on Gross Motor Coordination in Children Aged 8 to 10 Years.
Generally, adequate motor coordination (MC) ability is one among the critical factors for the overall development of children. In this paper, we have thoroughly analyzed the effects of equine-assistant activity (EAA) training on MC in children. For this purpose, MC test, specifically for children, was used to the Körperkoordinationstest für Kinder (KTK), and a total of 100 children, particularly those in 8 to 10 age, were equally separated into equine-assistant activity group (EAAG) and control group (CG), respectively. The EAAG group has attended a 14-week EAA training program, while the CG joined in physical education activity once per week. The experimental results have indicated that four indices of KTK test (i.e., backward walk [WB], height jump [HH], jumping sideways [JS] and moving sideways [MS], and motor quotient [MQ] score) showed significant differences ( ∗ P < 0.05) after a 14-week EAA training. Furthermore, the indices of physical fitness test, standing long jump (SLJ), and sit and reach (SAR) showed significant differences ( ∗ P < 0.05), but the handgrip (HG) increased slightly without significant difference (P > 0.05) after a 14-week EAA training. In conclusion, there were improvements in MC, lower limb strength, and flexibility by EAAG for those who participated in a 14-week EAA training, and this study has demonstrated the effectiveness of the KTK assessment of MC in children 8 to 10 years.


Ultrasound Assessment of the Rectus Femoris Cross-Sectional Area: Subject Position Implications.
Ultrasonic measurement of the rectus femoris (RF) is a novel, proxy measure for muscle strength. The impact of hip flexion/head of bed positioning on RF cross-sectional area (CSA) has not been fully explored. This study describes and compares differences in RF CSA across four degrees of hip flexion. This repeated-measures, comparative study enrolled healthy, pre-menopausal women (n = 20). RF CSA of the dominant leg was measured using the SonoSite M-Turbo ultrasound system with the head of bed at 0°, 20°, 30°, and 60°. One-way repeated measures indicated significant differences in RF CSA, F(3, 17) = 14.18, p < .001, with variation in hip flexion/head of bed elevation and significant RF CSA differences between: (a) 0° and 20°, (b) 0° and 30°, (c) 0° and 60°, and (d) 20° and 60°. Standardizing patient positioning when conducting ultrasonic measurement of RF CSA is vital for researchers who assess muscle mass.


Gigahertz acoustic vibrations of Ga-doped ZnO nanoparticle array.
In this work, we present an experimental study on the acoustic vibrations of ZnO nanoparticles array with different concentration of Ga dopings by using femtosecond pump-probe technique. The Ga-doped ZnO (GZO) nano-triangle particles with the sizes of 190, 232 and 348 nm are fabricated by nanosphere lithography and pulsed laser deposition method. The result indicates that the frequency of acoustic vibrations of GZO nanoparticles decrease as the Ga-concentration is increased. Importantly, the vibration period of the GZO nanoparticles at the same Ga doping concentration show a nonlinear increase as the nanoparticle size is increased, which is different from the common linear dependency in undoped ZnO nanoparticles. It may be attributed to the crystal structure distortion and elastic characteristics variation due to Ga doping, and the elastic modulus at 7.3% Ga doping is decreased by 30%-60% for GZO nanoparticles with different sizes. The study can be very helpful for evaluating the crystal structure distortion and elastic characteristics of doped nano-materials with optical methods. Besides, it can offer a complementary method of thermal management in ZnO based optoelectronic devices.


Adsorption Isotherms of Low-Pressure H2O on a Low-Temperature Surface Measured by a Quartz Crystal Microbalance.
The low-pressure gas in the vacuum plume produced by the chemical thrusters contaminates the spacecraft when adsorbed on the low-temperature surface. To provide theoretical support for further research on gaseous plume pollutants, the adsorption isotherms of low-pressure H2O were measured by a quartz crystal microbalance (QCM) at temperatures ranging from 233 to 273 K. The measured isotherms are similar to the type-I and type-II isotherms and have been correlated by various models (e.g., the Langmuir, Dubinin-Radushkevich, Brunauer-Emmett-Teller (BET), and universal models). It shows that the universal model has a great advantage in predicting the adsorption at a specific temperature point in our study. To estimate the adsorption at the continuous temperature range, the critical parameters of the multi-Langmuir model were expressed in semiempirical formulas. Since the normalized isotherms of H2O at different temperatures converge well, a simplified multi-Langmuir (SML) model was proposed. The experimental results at the temperature and pressure ranges we explored are consistent with the results predicted by the SML model, suggesting that the SML model is more suitable and convenient to predict the low-pressure adsorption of H2O for a continuous low-temperature range. Moreover, the low-pressure adsorption behaviors of H2O and CO2 on the low-temperature surface are compared and discussed.


Primary care perspectives on treating bipolar disorder: a cross-sectional survey.
In this study, we explored the comfort level of and influences upon primary care clinicians in prescribing psychotropic medications to patients with bipolar disorder. In May 2010, we mailed a 1-page survey to a cross-sectional sample of 143 primary care clinicians in 2 large practice groups asking physicians to specify whether they prescribe psychotropic medications to bipolar patients, describe their comfort level in prescribing psychotropic medications to this patient group, indicate possible influences on their willingness to prescribe psychotropics for bipolar patients, and provide their opinion on whether or not primary care physicians should prescribe these medications to bipolar patients. Of the 38 respondents (response rate of 26.6%), nearly two-thirds (n = 24) reported the prescription of psychotropic medications to bipolar patients in their practices. For questions related to bipolar diagnosis and treatment, the means of all responses trended toward uncomfortable, with the prescription of antipsychotics being indicated as the aspect with which respondents were least comfortable. As for factors influencing a decision to prescribe, the restricted availability of mental health services was rated as most influential. With regard to the perceived role of primary care clinicians in prescribing psychotropic medications to bipolar patients, no respondent indicated that primary care physicians should "always" prescribe, whereas approximately two-thirds indicated "rarely" or "on occasion." While a majority of primary care clinicians prescribe psychotropic medications to patients with bipolar disorder, a majority are also understandably hesitant to do so and appear to do so in particular circumstances, most likely related to the restricted availability of mental health services.


Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats.
Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis. Osteogenic differentiation of hPSCs with and without NELL-1 was tested in vitro. The results indicated that NELL-1 significantly increased the osteogenic potential of hPSCs in both osteoporotic and nonosteoporotic donors. Next, spinal fusion was performed by implanting scaffolds with regular or high doses of hPSCs, with or without NELL-1 in ovariectomized rats (n = 41). Regular doses of hPSCs or NELL-1 achieved the fusion rates of only 20%-37.5% by manual palpation. These regular doses had previously been shown to be effective in nonosteoporotic rat spinal fusion. Remarkably, the high dose of hPSCs+NELL-1 significantly improved the fusion rates among osteoporotic rats up to approximately 83.3%. Microcomputed tomography imaging and quantification further confirmed solid bony fusion with high dose hPSCs+NELL-1. Finally, histologically, direct in situ involvement of hPSCs in ossification was shown using undecalcified samples. To conclude, hPSCs combined with NELL-1 synergistically enhances spinal fusion in osteoporotic rats and has great potential as a novel therapeutic strategy for osteoporotic patients.


[Familial bilateral renal-cell carcinoma and cerebellar haemangioma (author's transl)].
In three brothers of a family with a high incidence of cancer a bilateral renal-cell carcinoma was demonstrated. In the index case there was also a cerebellar haemangioblastoma. At necropsy primary bilateral renal-cell carcinoma was demonstrated while intrarenal metastases were excluded. The cases are considered to be predominantly renal manifestations of the von Hippel-Lindau syndrome with facultative oculocerebellar involvement. Urological and cytogenetic study of other family members provided no evidence of further manifestations of the syndrome. Clinical supervision of members of such families is indicated.


Toward the biochemical assessment of myocardial fibrosis in hypertensive patients.
The serum concentrations of amino-terminal procollagen type III and carboxy-terminal procollagen type I-derived peptides, which have been proposed as useful markers of the tissue synthesis of collagen types III and type I, respectively, were abnormally increased in patients with essential hypertension and became normal after angiotensin-converting enzyme (ACE) inhibition. An association was found between baseline serum concentrations of these peptides and left ventricular hypertrophy, diastolic dysfunction, and ventricular arrhythmias in hypertensive patients. On the other hand, increased serum concentration of the carboxy-terminal procollagen type I-derived peptide was found in spontaneously hypertensive rats compared with normotensive Wistar-Kyoto control rats. An association was found between the serum concentration of this peptide and the extent of myocardial fibrosis and the hydroxyproline concentration in the left ventricle of spontaneously hypertensive rats. It is proposed that procollagen-derived peptides in serum may be markers of exaggerated collagen tissue synthesis involved in hypertensive myocardial fibrosis.


miR-139-3p/Kinesin family member 18B axis suppresses malignant progression of gastric cancer.
miR-139-3p exerts tumor-suppressing functions in various cancers. We analyzed and identified that miR-139-3p expression was notably low in gastric cancer (GC) via edgeR differential analysis based on The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction (qRT-PCR) assay. The binding relationship between Kinesin Family Member 18B (KIF18B) and miR-139-3p was predicted by bioinformatics databases, and verified through dual-luciferase assay. Western blot and qRT-PCR results also indicated that miR-139-3p restrained KIF18 expression at mRNA and protein levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell, flow cytometry assays were introduced to evaluate cell proliferation, migration, invasion, and cell cycle, respectively, where the results indicated that upregulating miR-139-3p inhibited proliferative, migratory, and invasive abilities of GC cells, while caused cell-cycle arrest. Moreover, the results of rescue experiments illustrated that miR-139-3p hampered the progression of GC cells by targeting and suppressing KIF18B. To sum up, we concluded that miR-139-3p suppressed GC progression by targeting KIF18B.


Membrane topology of the Bacillus subtilis pro-sigma(K) processing complex.
Activation of the final sporulation-specific transcription factor, sigma(K), is regulated by a signal emanating from the forespore which interacts with the pro-sigma(K) processing complex, comprising SpoIVFA, BofA, and the pro-sigma(K) processing protease, SpoIVFB. Mature sigma(K) then directs late gene expression in the parental compartment of the developing sporangial cell. The nature of this complex and how it is activated to process pro-sigma(K) are not understood. All three proteins are predicted to be integral membrane proteins. Here, we have analyzed the membrane topology of SpoIVFA and SpoIVFB by constructing chimeric forms of spoIVFA and spoIVFB with the complementary reporters phoA and lacZ and analyzing activity in Escherichia coli. SpoIVFA was found to have a single transmembrane-spanning domain, while SpoIVFB was shown to have six transmembrane-spanning domains (6-transmembrane configuration). Further, SpoIVFA is required to stabilize SpoIVFB in the membrane. SpoIVFB was shown to have a 4-transmembrane configuration when expressed on its own but was found to have a 6-transmembrane configuration when coexpressed with SpoIVFA, while BofA had a positive effect on the assembly of both SpoIVFA and SpoIVFB. The single transmembrane domain of SpoIVFA (approximately residues 73 to 90) was shown to be the principle determinant in stabilizing the 6-transmembrane configuration of SpoIVFB. Although the bofB8 allele, which uncouples the sigma(K) checkpoint, did not appear to promote a conformational change from a 6- to 4-transmembrane configuration of SpoIVFB (apparently ruling out a profound conformational change as the mechanism of activating SpoIVFB proteolytic activity), instability of SpoIVFB may be an important factor in SpoIVFB-mediated processing of pro-sigma(K).


Exploring salivary microbiota in AIDS patients with different periodontal statuses using 454 GS-FLX Titanium pyrosequencing.
Patients with acquired immunodeficiency syndrome (AIDS) are at high risk of opportunistic infections. Oral manifestations have been associated with the level of immunosuppression, these include periodontal diseases, and understanding the microbial populations in the oral cavity is crucial for clinical management. The aim of this study was to examine the salivary bacterial diversity in patients newly admitted to the AIDS ward of the Public Health Clinical Center (China). Saliva samples were collected from 15 patients with AIDS who were randomly recruited between December 2013 and March 2014. Extracted DNA was used as template to amplify bacterial 16S rRNA. Sequencing of the amplicon library was performed using a 454 GS-FLX Titanium sequencing platform. Reads were optimized and clustered into operational taxonomic units for further analysis. A total of 10 bacterial phyla (106 genera) were detected. Firmicutes, Bacteroidetes, and Proteobacteria were preponderant in the salivary microbiota in AIDS patients. The pathogen, Capnocytophaga sp., and others not considered pathogenic such as Neisseria elongata, Streptococcus mitis, and Mycoplasma salivarium but which may be opportunistic infective agents were detected. Dialister pneumosintes, Eubacterium infirmum, Rothia mucilaginosa, and Treponema parvum were preponderant in AIDS patients with periodontitis. Patients with necrotic periodontitis had a distinct salivary bacterial profile from those with chronic periodontitis. This is the first study using advanced sequencing techniques focused on hospitalized AIDS patients showing the diversity of their salivary microbiota.


[The fixed human lymphocytes as a source of DNA for polymerase chain reaction diagnostic.]
The article presents the results of studying of quantitative and qualitative characteristics of DNA samples separated by sorbate technique from human lymphocytes went through ethanol acetic fixation for preparation of cytogenetic specimen. The concentration of DNA varied within range 18.9-213.2 ng per mkl. The rate A260/A280 amounted to 1.47-2.53. All samples were found suitable for application of polymerase chain reaction during detection of AZF-deletions of Y-chromosome. The considered mode of separation of DNA is highly efficient in respect of fixed lymphocytes and it can be applied in medical biologic studies.


AlphaPIX and betaPIX and their role in focal adhesion formation.
Alpha and betaPIX belong to the group of guanine nucleotide exchange factors (GEFs) that mediate activation of members of the Rho GTPase family, in particular Rac1 and Cdc42, by stimulating the exchange of GDP for GTP. Rho family proteins are well known as regulators of the actin cytoskeleton and have been implicated in the formation of various types of focal adhesion structures. However, the function of GEF proteins during focal adhesion formation is only beginning to emerge. Here, we highlight the recent findings on alpha and betaPIX and their involvement in integrin-dependent signaling and suggest models for the role of PIX proteins during focal adhesion turnover.


Nematotoxicity of a Cyt-like protein toxin from Conidiobolus obscurus (Entomophthoromycotina) on the pine wood nematode Bursaphelenchus xylophilus.
The pine wood nematode Bursaphelenchus xylophilus is a destructive pest on Pinus trees and lacks effective control measures. The present study identified a novel nematotoxic cytolytic (Cyt)-like protein originating from the entomopathogenic fungus Conidiobolus obscurus. The protein was successfully purified using heterologous expression in Escherichia coli and affinity chromatography. N-hydroxysuccinimide-rhodamine-labeled Cyt-like protein was used to establish the route of toxin uptake, and revealed that the toxin can enter the nematode via the stylet. In bioassays, the purified protein had high nematicide activity against B. xylophilus, with a median lethal concentration at 24 h of 15.8 and 29.4 μg mL-1 for juveniles and adults, respectively. Compared with the deionized water control, fecundity, thrashing, and egg hatching were significantly reduced by 97%, 98%, and 83%, respectively, with 40 μg mL-1 Cyt-like protein at 24-36 h. Staining with Oil-Red-O showed a decrease in large lipid droplet formation in the protein-treated adult nematodes. The Cyt-like protein toxin possesses high nematicide activity against B. xylophilus with effects on nematode vitality and fecundity. The potential exists to use the Cyt-like protein for the control of B. xylophilus.


Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis.
Interleukin-6 (IL-6) plays a crucial role in systemic autoimmunity and pathologic inflammation. Numerous studies have explored serum IL-6 levels in systemic lupus erythematosus (SLE) and their correlation with disease activity. Here, we performed a meta-analysis to quantitatively assess the correlation between the serum IL-6 levels and SLE activity. The PubMed and EMBASE databases were thoroughly searched for relevant studies up to September 2019. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were used to describe the differences between serum IL-6 levels in SLE patients and healthy controls and between those in active SLE patients and inactive SLE patients. The correlation between the serum IL-6 levels and disease activity was evaluated using Fisher's z values. A total of 24 studies involving 1817 SLE patients and 874 healthy controls were included in this meta-analysis. Serum IL-6 levels were significantly higher in SLE patients than in the healthy controls (pooled SMD: 2.12, 95% CI: 1.21-3.03, Active SLE patients had higher serum IL-6 levels than inactive SLE patients (pooled SMD: 2.12, 95% CI: 1.21-3.03). Furthermore, the pooled Fisher's z values (pooled Fisher's z=0.36, 95% CI: 0.26-0.46, p<0.01) showed that there was a positive correlation between the serum IL-6 levels and SLE activity. This study suggested that serum IL-6 levels were higher in patients with SLE than in healthy controls, and they were positively correlated with disease activity when Systemic Lupus Erythematosus Disease Activity Index>4 was defined as active SLE. More homogeneous studies with large sample sizes are warranted to confirm our findings due to several limitations in our meta-analysis.


Multimodal imaging assessment of a "micro" optic disk melanocytoma: A case report.
An optic disk melanocytoma is a benign pigmented neoplasm of the optic disk measuring 2.00 mm of diameter in average. Smaller optic disk melanocytomas are rare and have not been studied with multiple imaging studies. A case of a "micro" optic disk melanocytoma measuring 0.71 mm in diameter was studied by multiple imaging modalities, including fundus autofluorescence, ultrasound, visual fields, optical coherence tomography (OCT) and OCT angiography. While clinical appreciation and fundus autofluorescence reveal changes compatible with previously reported cases, OCT, OCT angiography and ultrasound reveal specific changes that could be useful for follow up.


Residents working with Médecins Sans Frontières: training and pilot evaluation.
Well-prepared humanitarian workers are now more necessary than ever. Essential to the preparation process are: clearly defined learning objectives, curricula tailored to the nuances of humanitarian settings, simulation-based training, and evaluation. This manuscript describes a training program designed to prepare medical residents for their first field deployment with Médecins Sans Frontières and presents the results of a pilot assessment of its effectiveness. The training was jointly developed by the Research Center in Emergency and Disaster Medicine- CRIMEDIM of the Università del Piemonte Orientale, Novara, Italy, and the humanitarian aid organization Médecins Sans Frontières- Italy (MSF-Italy); the following topics were covered: disaster medicine, public health, safety and security, infectious diseases, psychological support, communication, humanitarian law, leadership, and job-specific skills. It used a blended-learning approach consisting of a 3-month distance learning module; 1-week instructor-led coaching; and a field placement with MSF. We assessed its effectiveness using the first three levels of Kirkpatrick's training evaluation model. Eight residents took part in the evaluation. Four were residents in emergency medicine, 3 in anesthesia, and 1 in pediatrics; 3 of them were female and the median age was 31 years. Two residents were deployed in Pakistan, 1 in Afghanistan, 1 in the Democratic Republic of Congo, 1 in Iraq, 2 in Haiti and 1 on board of the MSF Mediterranean search & rescue ship. Mean deployment time was 3 months. The average median score for the overall course was 5 (excellent). There was a significant improvement in post-test multiple choice scores (p = 0.001) and in residents' overall performance scores (P = 0.000001). Residents were highly satisfied with the training program and their knowledge and skills improved as a result of participation. This study was approved by the Institutional Ethics Committee (date 24-02-2016, study code UPO.2015.4.10).


[Surgical results of postinfarction ventricular septal perforation: operative planning using "endocardial patch repair with infarct exclusion"].
Between 1983 and 1996, twenty-two consecutive patients underwent surgical repair for postinfarction ventricular perforation (VSP). Overall hospital mortality was 31.8% in the reviewed group. 15 patients were operated upon within two weeks of onset of VSP and hospital mortality was 27.3% in this group. The earlier operation might provide more favorable results in the surgery of VSP. When the preoperative coronary angiography revealed multivessel disease, concomitant myocardial revascularization was performed. In recent 2 cases, we employed the new technique introduced by Komeda and David for the reconstruction of the left ventricule using a single pericardial patch. We found this new technique had many advantages over traditional "Daggett's method". Better operative results could be expected with this technique.


Cell-cell adhesion prevents mutant cells lacking myosin II from penetrating aggregation streams of Dictyostelium.
When a small number of fluorescently labeled myosin II mutant cells (mhcA-) are mixed with wild-type cells and development of the chimeras is observed by confocal microscopy, the mutant cells are localized to the edges of aggregation streams and mounds. Moreover, the mutant cells stick to wild-type cells and become distorted (Shelden and Knecht, 1995). Two independent adhesion mechanisms, Contact Sites A and Contact Sites B, function during the aggregation stage and either one or both might be responsible for excluding the myosin II null cells. We have mixed mhcA- cells with cells in which the appearance of Contact Sites B is delayed (strain TL72) as well as cells which lack Contact Sites A (strain GT10) and double mutants in which both adhesion mechanisms are affected (strain TL73). In all chimeras, the mhcA- cells were distorted by interactions with the adhesion mutant cells, indicating that it does not require significant adhesive interaction to distort the flaccid cortex of mhcA- cells mhcA- cells were excluded from streams composed of cells lacking either Contact Sites A or Contact Sites B but mixed randomly with cells lacking both adhesion systems. By 10 hr of development, cells of strain TL73 acquire Contact Sites B adhesion. If cells of this strain were mixed with labeled mhcA- cells, allowed to develop for 9 hr, and then dissociated before replating, the myosin II null cells were seen to be distorted and excluded from the reaggregates. Thus, the exclusion of mhcA- cells from streams can be accomplished by either Contact Sites A or B. When chimeras of labeled TL73 and wild-type cells were made, the TL73 cells were found to be randomly mixed into aggregation streams. This result indicates that adhesive sorting does not function during aggregation and so cannot account for the exclusion of mhcA- cells from streams. We hypothesize that the flaccid cortex of mhcA- cells cannot generate sufficient protrusive force to break the contacts between adhered cells in aggregation streams but can enter streams where the cells are weakly adherent.


[Oral manifestations of KID syndrome: rare clinical case].
The paper presents a rare clinical case of an infant with KID (Keratitis, Ichthyosis, Deafness) syndrome (about 100 patients reported so far) admitted for histological verification of oral mucosa lesions. Disease pathogenesis defines inadequate reparation and skin and mucosa innate immunity defect leading to higher incidence of bacterial and fungal infections, so the 4-years old girl received treatment for vegetating candidiasis of the oral mucosa for several weeks with no clinical improvement. Initial examination showed that the oral lesions resulted from sharp edges of severely affected carious teeth. Histological study of multifocal biopsy revealed pyogenic granulomas and no signs of SCC. Teeth extraction and symptomatic treatment leaded to significant clinical improvement and some remained mucosal changes may be attributed to syndrome manifestations.


Immunology of stiff person syndrome and other GAD-associated neurological disorders.
Antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of GABA, are associated with an array of distinct, mostly autoimmune, neurological conditions. In all associated syndromes, namely stiff person syndrome, cerebellar ataxia, epilepsy, limbic encephalitis or abnormal eye movements, anti-GAD antibodies are detected at high titers and play a fundamental role in diagnosis, but do not correlate with disease severity, diversity of symptomatology or response to therapies. Despite considerable efforts, including in vitro (enzymatic assays) and in vivo (animal models) systems, the pathogenicity of anti-GAD antibodies has not been unequivocally proven for any specific condition. The search for the responsible autoantigen has revealed a few other antigenic targets, particularly for SPS, localized in the pre- or post-synaptic inhibitory neuronal synapses. Cumulative clinical and laboratory evidence indicates that anti-GAD and related antibodies define a novel group of syndromes, collectively known as 'hyperexcitability disorders'.


The glycoforms of a Trypanosoma brucei variant surface glycoprotein and molecular modeling of a glycosylated surface coat.
The plasma membrane of the African sleeping sickness parasite Trypanosoma brucei is covered with a dense, protective surface coat. This surface coat is a monolayer of five million variant surface glycoprotein (VSG) dimers that form a macromolecular diffusion barrier. The surface coat protects the parasite from the innate immune system and, through antigenic variation, the specific host immune response. There are several hundred VSG genes per parasite, and they encode glycoproteins that vary in primary amino acid sequence, the number of N-glycosylation sites, and the types of N-linked oligosaccharides and glycosylphosphatidylinositol membrane anchors they contain. In this study, we show that VSG MITat.1.5 is glycosylated at all three potential N-glycosylation sites, and we assign the oligosaccharides present at each site. Using the most abundant oligosaccharides at each site, we construct a molecular model of the glycoprotein to assess the role of N-linked oligosaccharides in the architecture of the surface coat.


Colonic interleukin-22 protects intestinal mucosal barrier and microbiota abundance in severe acute pancreatitis.
Intestinal barrier dysfunction plays a critical role in the pathophysiology of many diseases including severe acute pancreatitis (SAP). Interleukin-22 (IL-22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site, and characteristics of IL-22 in the intestinal barrier dysfunction remains elusive. Studies were conducted in patients with SAP and SAP mice model. SAP mice model was induced by intraductal infusion of 5% taurocholic acid. The level and source of IL-22 were analyzed by flow cytometry. The effect of IL-22 in SAP-associated intestinal injury were examined through knockout of IL-22 (IL-22-/- ) or administration of recombinant IL-22 (rIL-22). IL-22 increased in the early phase of SAP but declined more quickly than that of proinflammatory cytokines, such as IL-6 and TNF-α. CD177+ neutrophils contributed to IL-22 expression in SAP. IL-22 was activated in the colon rather than the small intestine during SAP. Deletion of IL-22 worse the severity of colonic injury, whereas administration of rIL-22 reduced colonic injury. Mechanistically, IL-22 ameliorates the intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E-cadherin and ZO-1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. This study revealing that early decreased colonic IL-22 aggravates intestinal mucosal barrier dysfunction and microbiota dysbiosis in SAP. Colonic IL-22 is likely a promising treating target in the early phase of SAP management. Research in context Evidence before this study Intestinal barrier dysfunction plays a critical role in the pathophysiology of severe acute pancreatitis (SAP). Interleukin-22 (IL-22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site and characteristics of IL-22 in the intestinal barrier dysfunction remains elusive. Added value of this study Firstly, we determined the dynamic expression profile of IL-22 in SAP and found that IL-22 was mostly activated in the pancreas and colon and decreased earlier than proinflammatory cytokines. CD177+ neutrophils contributed to IL-22 expression in SAP. Furthermore, we found that IL-22 ameliorates intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E-cadherin and ZO-1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. Implications of all the available evidence This study highlights the role of colonic injury and colonic IL-22 in SAP. IL-22 is likely a promising treating target in the early phase of SAP management.


Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker.
Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.


Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia.
Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.


Harvest: an open-source tool for the validation and improvement of peptide identification metrics and fragmentation exploration.
Protein identification using mass spectrometry is an important tool in many areas of the life sciences, and in proteomics research in particular. Increasing the number of proteins correctly identified is dependent on the ability to include new knowledge about the mass spectrometry fragmentation process, into computational algorithms designed to separate true matches of peptides to unidentified mass spectra from spurious matches. This discrimination is achieved by computing a function of the various features of the potential match between the observed and theoretical spectra to give a numerical approximation of their similarity. It is these underlying "metrics" that determine the ability of a protein identification package to maximise correct identifications while limiting false discovery rates. There is currently no software available specifically for the simple implementation and analysis of arbitrary novel metrics for peptide matching and for the exploration of fragmentation patterns for a given dataset. We present Harvest: an open source software tool for analysing fragmentation patterns and assessing the power of a new piece of information about the MS/MS fragmentation process to more clearly differentiate between correct and random peptide assignments. We demonstrate this functionality using data metrics derived from the properties of individual datasets in a peptide identification context. Using Harvest, we demonstrate how the development of such metrics may improve correct peptide assignment confidence in the context of a high-throughput proteomics experiment and characterise properties of peptide fragmentation. Harvest provides a simple framework in C++ for analysing and prototyping metrics for peptide matching, the core of the protein identification problem. It is not a protein identification package and answers a different research question to packages such as Sequest, Mascot, X!Tandem, and other protein identification packages. It does not aim to maximise the number of assigned peptides from a set of unknown spectra, but instead provides a method by which researchers can explore fragmentation properties and assess the power of novel metrics for peptide matching in the context of a given experiment. Metrics developed using Harvest may then become candidates for later integration into protein identification packages.


Sequence organization and insertion specificity of the novel chimeric ISHp609 transposable element of Helicobacter pylori.
Here we describe ISHp609 of Helicobacter pylori, a new member of the IS605 mobile element family that is novel and contains two genes whose functions are unknown, jhp960 and jhp961, in addition to homologs of two other H. pylori insertion sequence (IS) element genes, orfA, which encodes a putative serine recombinase-transposase, and orfB, whose homologs in other species are also often annotated as genes that encode transposases. The complete four-gene element was found in 10 to 40% of strains obtained from Africa, India, Europe, and the Americas but in only 1% of East Asian strains. Sequence comparison of 10 representative ISHp609 elements revealed higher levels of DNA sequence matches (99%) than those seen in normal chromosomal genes (88 to 98%) or in other IS elements (95 to 97% for IS605, IS606, and IS607) from the same H. pylori populations. Sequence analysis suggested that ISHp609 can insert at many genomic sites with its left end preferentially next to TAT, with no target specificity for its right end, and without duplicating or deleting target sequences. A deleted form of ISHp609, containing just jhp960 and jhp961 and 37 bp of orfA, found in reference strain J99, was at the same chromosomal site in 15 to 40% of the strains from many geographic regions but again in only 1% of the East Asian strains. The abundance and sequence homogeneity of ISHp609 and of this nonmobile remnant suggested a recent bottleneck and then rapid spread in H. pylori populations, possibly selected by the contributions of the elements to bacterial fitness.


Effect of acute exhausting exercise on cytokine gene expression in men.
Because of recent interest in the effects of physical exercise on immunologic function, we decided to use state-of-the-art methods to evaluate cytokines in the peripheral blood leukocytes (PBLs) of 7 men before and after a maximal treadmill stress test. Change in cytokine gene expression was quantified from PBLs using a reverse transcriptase polymerase chain reaction assay (RT-PCR). In contrast to reports on serum levels or using in vitro testing, direct gene expression of TNF-alpha decreased after the stress test (p < 0.008). However, the 47% decrease was relatively small and of questionable biological significance. Levels of IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-10, and INF-gamma did not change.


Effects of (R)-deoxycoformycin (pentostatin) on intrauterine nucleoside catabolism and embryo viability in the pregnant mouse.
The viability of early mouse embryos is acutely sensitive to (R)-deoxycoformycin (pentostatin), a tight-binding inhibitor of adenosine deaminase (ADA). Previous studies have shown that a single 5-mg/kg dose on day 7 (plug = day 0) of gestation fully inhibits uteroplacental ADA activity within 0.5 h; causes massive cell death in the neural plate and primary mesenchyme by 6 h, major craniofacial anomalies by day 10, and resorption by day 12 (Knudsen et al., '89; Airhart et al., '91). The present study has examined further the developmental toxicity and early effects of this inhibitor on ADA metabolism. (R)-Deoxycoformycin was administered to pregnant CD-1 (ICR) mice as a single intraperitoneal dose of 0.5-10 mg/kg total body weight on days 6-11 of gestation. The major adverse effect, early resorption, was dose dependent and specific to day 7-8 exposure. Treatment with 5 mg/kg on day 7 resulted in 85% resorptions, 15% malformations, and a 24% reduction in mean fetal weight, whereas the same dose of (S)-deoxycoformycin had no effect. Levels of adenosine and 2'-deoxyadenosine, which are the endogenous substrates of ADA, were monitored in the embryo/decidual unit (E/D) by reversed-phase high-performance liquid chromatography (RP-HPLC). In response to the inhibitor, both nucleosides increased transiently in the antimesometrial compartment (antimesometrial decidua + embryo). Peak levels (Cmax) of adenosine and 2'-deoxyadenosine were dose dependent over the range tested (0.05-10 mg/kg). Exposure to 5 mg/kg on day 7 raised adenosine levels within 0.5 h to 42-fold over the basal level of 0.06 nmol/mg protein. There was an even stronger effect on 2'-deoxyadenosine levels, which were elevated 674-fold over the detection limit of 0.0005 nmol/mg protein. Direct exposure to the inhibitor in serum-free E/D culture produced similar results: 50 microM (R)-deoxycoformycin within 1 h raised adenosine levels 26-fold and 2'-deoxyadenosine levels 410-fold. In vivo studies also showed a general correlation between embryolethality and the length of adenine nucleoside pool expansion, apparent for exposure on day 7, 8, or 9 but not on day 6, suggesting that the embryo becomes sensitive to adenosine or 2'-deoxyadenosine once the neural plate has formed.


Genetic variability and population structure of Ethiopian chickpea (Cicer arietinum L.) germplasm.
Evaluation of the genetic diversity and an understanding of the genetic structure and relationships of chickpea genotypes are valuable to design efficient germplasm conservation strategies and crop breeding programs. Information is limited, in these regards, for Ethiopian chickpea germplasms. Therefore, the present study was carried out to estimate the genetic diversity, population structure, and relationships of 152 chickpea genotypes using simple sequence repeats (SSR) markers. Twenty three SSR markers exhibited polymorphism producing a total of 133 alleles, with a mean of 5.8 alleles per locus. Analyses utilizing various genetic-based statistics included pairwise population Nei's genetic distance, heterozygosity, Shannon's information index, polymorphic information content, and percent polymorphism. These analyses exemplified the existence of high genetic variation within and among chickpea genotypes. The 152 genotypes were divided into two major clusters based on Nei's genetic distances. The exotic genotypes were grouped in one cluster exclusively showing that these genotypes are distinct to Ethiopian genotypes, while the patterns of clustering of Ethiopian chickpea genotypes based on their geographic region were not consistent because of the seed exchange across regions. Model-based population structure clustering identified two discrete populations. These finding provides useful insight for chickpea collections and ex-situ conservation and national breeding programs for widening the genetic base of chickpea.