Enhancement of Antigen Presentation by Deletion of Viral Immune Evasion Genes Prevents Lethal Cytomegalovirus Disease in Minor Histocompatibility Antigen-Mismatched Hematopoietic Cell Transplantation.
Hematoablative treatment followed by hematopoietic cell transplantation (HCT) for reconstituting the co-ablated immune system is a therapeutic option to cure aggressive forms of hematopoietic malignancies. In cases of family donors or unrelated donors, immunogenetic mismatches in major histocompatibility complex (MHC) and/or minor histocompatibility (minor-H) loci are unavoidable and bear a risk of graft-vs.-host reaction and disease (GvHR/D). Transient immunodeficiency inherent to the HCT protocol favors a productive reactivation of latent cytomegalovirus (CMV) that can result in multiple-organ CMV disease. In addition, there exists evidence from a mouse model of MHC class-I-mismatched GvH-HCT to propose that mismatches interfere with an efficient reconstitution of antiviral immunity. Here we used a mouse model of MHC-matched HCT with C57BL/6 donors and MHC-congenic BALB.B recipients that only differ in polymorphic autosomal background genes, including minor-H loci coding for minor-H antigens (minor-HAg). Minor-HAg mismatch is found to promote lethal CMV disease in absence of a detectable GvH response to an immunodominant minor-HAg, the H60 locus-encoded antigenic peptide LYL8. Lethality of infection correlates with inefficient reconstitution of viral epitope-specific CD8+ T cells. Notably, lethality is prevented and control of cytopathogenic infection is restored when viral antigen presentation is enhanced by deletion of immune evasion genes from the infecting virus. We hypothesize that any kind of mismatch in GvH-HCT can induce "non-cognate transplantation tolerance" that dampens not only a mismatch-specific GvH response, which is beneficial, but adversely affects also responses to mismatch-unrelated antigens, such as CMV antigens in the specific case, with the consequence of lethal CMV disease.


Semi-Lagrangian off-lattice Boltzmann method for weakly compressible flows.
The lattice Boltzmann method is a simulation technique in computational fluid dynamics. In its standard formulation, it is restricted to regular computation grids, second-order spatial accuracy, and a unity Courant-Friedrichs-Lewy (CFL) number. This paper advances the standard lattice Boltzmann method by introducing a semi-Lagrangian streaming step. The proposed method allows significantly larger time steps, unstructured grids, and higher-order accurate representations of the solution to be used. The appealing properties of the approach are demonstrated in simulations of a two-dimensional Taylor-Green vortex, doubly periodic shear layers, and a three-dimensional Taylor-Green vortex.


Thyroid Imaging Reporting and Data System (TI-RADS): A User's Guide.
In 2017, the Thyroid Imaging Reporting and Data System (TI-RADS) Committee of the American College of Radiology (ACR) published a white paper that presented a new risk-stratification system for classifying thyroid nodules on the basis of their appearance at ultrasonography (US). In ACR TI-RADS, points in five feature categories are summed to determine a risk level from TR1 to TR5. Recommendations for biopsy or US follow-up are based on the nodule's ACR TI-RADS level and its maximum diameter. The purpose of this article is to offer practical guidance on how to implement and apply ACR TI-RADS based on the authors' experience with the system. © RSNA, 2018.


Role of repetitive transcranial magnetic stimulation in maintenance treatment of resistant depression.
Troublesome side-effects and lack of efficacy of the pharmacotherapy are the two major limitations in the depression treatment. Inspite of the established modalities like switching, combination and augmentation, using pharmacological and non-pharmacological agents, nearly one-third patients do not achieve complete remission. Repetitive Transcranial Magnetic Stimulation (rTMS) is one such somatic treatment which has been extensively studied for treatment for acute depression. Drop-out rates due to adverse effects have been found to be extremely low. However, literature regarding the role of rTMS in maintenance treatment in recurrent depression is scarce, and there is no existing literature from India. In this case-report we highlight the role of rTMS in the maintenance treatment of TRD in a patient who has been followed up for about three years (four episodes). Emphasis is placed on improvement in symptoms and functioning without use of any pharmacological treatment. Further, the need for systematic study and standardization of various aspects of rTMS therapy for maintenance treatment is emphasised.


Caprine herpesvirus 1 vaccine with the LTK63 mutant as a mucosal adjuvant induces strong protection against genital infection in goats.
Caprine herpesvirus 1 provides a unique virus-animal model to investigate potential tools applicable for the therapy and prophylaxis of genital herpesvirus infections of humans. In order to evaluate the efficacy of mucosal immunization in the goat model, an inactivated CpHV-1 vaccine was adjuvated with the enzymatically inactive mutant of the heat-labile enterotoxin of Escherichia coli, LTK63, and used to immunize goats by the vaginal route, by administering two doses at a 3-week interval. The mucosal vaccine was safe, as neither local nor systemic reactions were associated with the vaccine administration. The vaccinated animals displayed high levels of secretory IgA and were significantly protected after challenge with the virulent CpHV-1 strain, with marked decrease in virus shedding, while the unvaccinated goats were not. These findings suggest that mucosal immunization is potentially exploitable in the control of genital infection by herpesviruses.


Submicrometre resolution phase-contrast radiography with the beam from an X-ray waveguide.
Experimental data with unprecedented submicrometre resolution obtained in a phase-contrast radiography experiment in a magnifying configuration are presented. The term 'phase contrast' here indicates that the phase retardation of coherent light in matter was utilized as the contrast mechanism. The coherent and divergent beam exiting an X-ray waveguide was used in a lensless configuration to magnify spatial variations in optical path length up to several hundred times. The defocused image of a nylon fibre was measured with a resolution of 0.14 micro m at the object. Sufficient contrast was found for exposure times of 0.1 s, i.e. in the regime for real-time studies.


Naringenin enhances intestinal barrier function through the expression and cytoskeletal association of tight junction proteins in Caco-2 cells.
We have previously reported that naringenin promotes the tight junction (TJ) integrity in intestinal Caco-2 cells. This study investigated the naringenin-mediated effect in Caco-2 cells with a particular focus on the modulation of TJ structure and claudin-4 transcriptional regulation. Naringenin (10~100 μM) dose-dependently enhanced TJ barrier integrity of Caco-2 cells, indicated by transepithelial electrical resistance and FITC-dextran flux. Immunoblot analysis showed that naringenin increased the cytoskeletal association of TJ proteins, zonula occludens-2, occludin, claudin-1, and claudin-4, simultaneously with increased occludin phosphorylation. The total expression of claudin-4 was also increased by naringenin. Quantitative RT-PCR and luciferase reporter assay revealed that naringenin transcriptionally increased the claudin-4 expression with activation of claudin-4 promoter. The mutation of the binding site of the transcriptional factor Sp1 in the claudin-4 promoter sequence and the pharmacological inhibition of Sp1 partially suppressed the naringenin-mediated activation of the claudin-4 promoter. Further, naringenin induced the heat shock protein 70 expression in the cells. Naringenin enhances barrier integrity through the assembly and expression of TJ proteins in intestinal epithelial cells. Naringenin-mediated claudin-4 expression occurs, at least partially, through Sp1-dependent transcriptional regulation. The induction of heat shock protein 70 may be also involved in the increased claudin-4 expression.


Risk behavior score: a practical approach for assessing risk among men who have sex with men in Brazil.
HIV/AIDS epidemic is not well controlled, and multiple sexual behavior factors help explain high rates of HIV infection among men who have sex with men (MSM). This article proposes to exam the use of a potential risk behavior score for HIV infection, based on the type and number of sexual partners, and condom use, and their associated factors in a sample of MSM in Brazil. A cross sectional RDS (Respondent Driven Sampling) study was performed among 3738 MSM aged 18+ years old from ten Brazilian cities. The risk behavior score was composed by the number of male partners and anal condom use in the last year with steady, casual, and commercial partners. Most participants were 25+ years old (58.1%), non-white (83.1%), and single (84.9%). Final weighted ordinal logistic model showed that age≤25 years old (p=0.037), homosexual or bisexual identity (p<0.001), sexual initiation before 15-year-old (p<0.001), having sex with men only in the last 12 months (p<0.001), frequent alcohol and illicit drug use (p<0.001), and use of local sites to meet sexual partners in the last month were independently associated with higher scores of risky behavior. Specific strategies should be developed aimed at the MSM population. Additionally, pre-exposed prophylaxis (Prep) should be considered for those at higher score as a strategy for reducing risk for HIV infection in this population.


Aspirin: dissolution rates of two polymorphic forms.
Two polymorphic forms of aspirin were characterized; the rates of dissolution of single crystals and of tablets were studied. One forms dissolves 50 percent faster than the other.


Mitral Annular Systolic Velocities Predict Left Ventricular Wall Motion Abnormality During Dobutamine Stress Echocardiography.
Longitudinal systolic left ventricular contraction is complementary to the radial performance and can be assessed using tissue Doppler imaging (TDI). This study was performed to evaluate the contribution of mitral annular systolic velocities using TDI after dobutamine stress echocardiography (DSE). Fifty subjects with suspected coronary artery disease and chest pain were examined, using DSE as usual, as well as TDI imaging of the mitral annulus at the septal, lateral, inferior, anterior, posterior regions and the proximal anteroseptal region from the apical views, before and immediately after DSE. In 24 subjects the study was normal, while wall motion abnormality was seen in 26, 9 of them only after DSE. Mitral annular systolic velocity at the 6 locations increased significantly after DSE both in normal subjects and in those with wall motion abnormality (WMA). After DSE mitral annular septal systolic velocity in normals, 19.2 ± 3.8 cm/sec, was higher than in those with WMA, 14.6 ± 2.5 cm/sec, P < 0.0003. Post-DSE mitral systolic velocity was senstive and accurate in predicting WMA. Systolic mitral TDI velocities increase after DSE, however to a lesser extent in those with wall motion abnormality, and can differentiate them from normal subjects.


ELISA-determined serological reactivity against purified trichophytin in dermatophytosis.
Serological activity in 62 patients wih dermatophytosis was investigated using purified trichophytin preparation as antigen (produced by the ethylene glycol method). Antibodies of IgG and IgM classes were determined by means of ef enzyme linked immunosorbent assay (ELISA). In comparison with 79 controls consisting of groups of healthy blood donors and dermatological outpatients, the dermatophyte-infected patients showed a significantly higher mean IgG response to trichophytin antigen preparation. On the other hand several individual cases were low responders. In a group of 10 control children, no IgG activity against trichophytin could be demonstrated. IgM class antibodies showed no significant differences between the groups investigated. These findings indicate that differences in the amounts of antibodies of IgG class against trichophytin as measured by the ELISA method reflect differences in the degree of mycotic sensitization between groups of individuals having experienced varying degrees of exposure to dermatophytes. Nevertheless, the determination of IgG antibodies in dermatophytosis seems to be of limited clinical value.


Outcomes and predictors of early mortality after continuous-flow left ventricular assist device implantation as a bridge to transplantation.
Left ventricular assist devices (LVADs) are fast becoming standard of care for patients with advanced heart failure. However, despite continuous improvement in VAD technology, there remains a significant early postoperative morbidity and mortality in this extreme patient group. The aim of the current study was to explore the short-term outcomes and predictors for 90 day mortality in the patients after implantation of continuous-flow LVAD. Perioperative clinical, echocardiographic, hemodynamic, and laboratory data of 90 day survivors and nonsurvivors were collected and compared retrospectively. Multivariate logistic regression analysis was performed on univariate predictors for 90 day mortality with an entry criterion of p < 0.1. Between July 2006 and May 2012, 117 patients underwent implantation of a continuous-flow LVAD as a bridge to transplantation: 71 (60.7%) HeartMate II (Thoratec Corp, Pleasanton, CA) and 46 (39.3%) HVAD (HeartWare International, Framingham, MA). All-cause 90 day mortality was 17.1%. Multivariate analysis revealed higher preoperative central venous pressure (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.014-1.378; p = 0.033) and higher age (OR, 1.14; 95% CI, 1.01-1.38; p = 0.045) as the only independent predictors for 90 day mortality. Optimization of preoperative volume status, preload, and right heart function as well as age-based selection of candidates for LVAD support are the critical factors influencing early outcome after continuous-flow LVAD implantation.


Prevention of sudden cardiac death: from wearable to subcutaneous cardioverter defibrillator.
The implantable cardioverter defibrillator (ICD) is today an indisputable evidence-based treatment for cardiac sudden death both in primary and secondary prevention. However many clinical conditions that would represent an indication to ICD implantation, according to guidelines, may be potentially reversible or may be accompanied by temporary contraindications to the implant. Moreover transvenous cardioverter defibrillator implantation still carries a not negligible risk of complications both acutely and at follow-up. The Wearable Cardioverter Defibrillator and the Subcutaneous Defibrillator are two recently developed technologies that can potentially overcome the aforementioned limitations of traditional transvenous ICDs. This review will discuss the main aspects of these 2 technologies, the data coming from clinical experiences and future perspectives.


Adult community-acquired pneumonia in central London.
Strep. pneumoniae was diagnosed as the cause of pneumonia in 40 (50%) of 80 consecutive adults admitted to St Stephen's Hospital with community-acquired pneumonia. None of the patients had evidence of Mycoplasma pneumoniae infection, and Legionella pneumophila serology was positive on only one occasion. In 29 patients (36%) no causative organism was demonstrated. The diagnosis of pneumococcal infection was obtained in 15 cases by isolating Strep. pneumoniae from the sputum, in 13 further cases by demonstrating pneumococcal capsular antigen in sputum, and in 12 other cases by detecting pneumococcal antigen in serum only. Only 2 cases with pneumococcal pneumonia were bacteraemic and 3 patients (7%), all aged more than 75 years, died. The relatively low bacteraemic and mortality rates suggest that community-acquired pneumococcal pneumonia currently seen in patients admitted to hospital in central London may not be so severe as in some other areas.


Analysis of Longevity Traits in Holstein Cattle: A Review.
Dairy cow longevity is an essential economic trait that can supplement the breeding value of production traits, which is related to the herd time and lifetime milk yield of dairy cows. However, longevity is a relatively difficult trait to select for dairy cow breeding due to low heritability and numerous influence factors of the longevity in dairy cows. Longevity trait has been used as an important breeding target of a comprehensive selection index in many dairy developed countries; however, it has not been included in performance index in many developing countries. At present, cows in these countries are still in the primary stage of "large quantity, low quality, high cost, and low yield." The average parity of dairy cows is less than 2.7, which is difficult to maintain the production efficiency to meet the demands of the dairy industry. Therefore, there is an urgent need to select and breed for the longevity of dairy cows. The various definitions and models (including linear, threshold, random regression, sire, and survival analysis) of longevity were reviewed and standardized. Survival analysis is the optimal model to evaluate longevity, and the longevity heritability is 0.01-0.30 by using different definitions and models. Additionally, the relationship between longevity and other traits was summarized, and found that longevity was regulated by multiple factors, and there were low or medium genetic correlations between them. Conformation traits, milk production traits, reproductive traits, and health traits may be used as indicators to select and breed the longevity of dairy cows. The genetic assessment methods, heritability, influencing factors, importance, breeding, and genetics of longevity were reviewed in the manuscript, which could provide a valuable reference for the selective breeding to extend the productive life of Holstein cattle.


In silico exploration of c-KIT inhibitors by pharmaco-informatics methodology: pharmacophore modeling, 3D QSAR, docking studies, and virtual screening.
c-KIT is a component of the platelet-derived growth factor receptor family, classified as type-III receptor tyrosine kinase. c-KIT has been reported to be involved in, small cell lung cancer, other malignant human cancers, and inflammatory and autoimmune diseases associated with mast cells. Available c-KIT inhibitors suffer from tribulations of growing resistance or cardiac toxicity. A combined in silico pharmacophore and structure-based virtual screening was performed to identify novel potential c-KIT inhibitors. In the present study, five molecules from the ZINC database were retrieved as new potential c-KIT inhibitors, using Schrödinger's Maestro 9.0 molecular modeling suite. An atom-featured 3D QSAR model was built using previously reported c-KIT inhibitors containing the indolin-2-one scaffold. The developed 3D QSAR model ADHRR.24 was found to be significant (R2 = 0.9378, Q2 = 0.7832) and instituted to be sufficiently robust with good predictive accuracy, as confirmed through external validation approaches, Y-randomization and GH approach [GH score 0.84 and Enrichment factor (E) 4.964]. The present QSAR model was further validated for the OECD principle 3, in that the applicability domain was calculated using a "standardization approach." Molecular docking of the QSAR dataset molecules and final ZINC hits were performed on the c-KIT receptor (PDB ID: 3G0E). Docking interactions were in agreement with the developed 3D QSAR model. Model ADHRR.24 was explored for ligand-based virtual screening followed by in silico ADME prediction studies. Five molecules from the ZINC database were obtained as potential c-KIT inhibitors with high in -silico predicted activity and strong key binding interactions with the c-KIT receptor.


Palliative Care Clinicians Caring for Patients Before and After Continuous Flow-Left Ventricular Assist Device.
Left ventricular assist devices (LVADs) are an available treatment option for carefully selected patients with advanced heart failure. Initially developed as a bridge to transplantation, LVADs are now also offered to patients ineligible for transplantation as destination therapy (DT). Individuals with a DT-LVAD will live the remainder of their lives with the device in place. Although survival and quality of life improve with LVADs compared with medical therapy, complications persist including bleeding, infection, and stroke. There has been increased emphasis on involving palliative care (PC) specialists in LVAD programs, specifically the DT-LVAD population, from the pre-implantation process through the end of life. Palliative care specialists are well poised to provide education, guidance, and support to patients, families, and clinicians throughout the LVAD journey. This article addresses the complexities of the LVAD population, describes key challenges faced by PC specialists, and discusses opportunities for building collaboration between PC specialists and LVAD teams.


Relationship between in vivo airway reactivity and in vitro responsiveness of tracheal smooth muscle in inbred rats.
We evaluated the in vivo and in vitro airway responses to cholinergic stimulation in two highly inbred strains of rats. Five Fisher and six Lewis rats inhaled aerosols of doubling concentrations of methacholine (MCh). Pulmonary resistance (RL) was measured before and after each MCh inhalation. The concentration of MCh required to double RL (EC200RL MCh) was calculated. Spirally cut tracheal strips were suspended in an organ bath and the isometric tension was recorded. Cumulative concentration-response curves to carbachol were obtained using concentrations ranging from 10(-9) to 10(-3) M in half-log increments. The maximum tension (Tmax) developed and the negative log of the molar concentration required to induce 50% of Tmax (pD2) were calculated. The geometric mean of ED200RL MCh for the Fisher group was significantly lower than that for the Lewis group (0.68 and 2.66 mg/ml, respectively; p less than 0.05). No significant difference was found for Tmax (0.67 +/- 0.11 vs. 0.50 +/- 0.11 g) and pD2 value (6.24 +/- 0.08 vs. 6.21 +/- 0.22 -log M), indicating a similar contraction of tracheal smooth muscle. We therefore conclude that (1) in vivo airway responsiveness is strain-related and genetically determined in the rat; (2) that there is no correlation between in vivo and in vitro airway response to cholinergic stimulation and (3) that intrinsic properties of airway smooth muscle do not account for the differences observed in airway responsiveness in vivo.


Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase.
Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the production of prostaglandin D and its J series metabolites. We evaluated the antiinflammatory effect of retrovirally transfected H-PGDS in order to investigate the role of H-PGDS in monosodium urate monohydrate (MSU) crystal-induced acute inflammation. Expression of endogenous PGDS in a murine air-pouch model of MSU crystal-induced acute inflammation was determined by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation was investigated. Injection of the crystals caused a rapid decrease in H-PGDS expression by infiltrating cells and by the soft tissues around the air pouches. In contrast, expression of interleukin-1beta (IL-1beta) and macrophage inflammatory protein 2 (MIP-2) as well as cellular infiltration were significantly increased during the early stage of inflammation. C57-PGDS cells, but not control cells, produced an increased amount of PGD(2) in vitro, but suppressed production of PGE(2). Injection of C57-PGDS cells into air pouches inhibited cellular infiltration and MIP-2 and IL-1beta expression. In this murine air-pouch model of MSU crystal-induced inflammation, retrovirally transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by inhibiting MIP-2 and IL-1beta. These findings suggest that gene therapy with H-PGDS may be useful for treating inflammatory diseases.


A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma.
Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low-pass sequencing data, and a set of 56 cancer-related genes were screened using an oncology panel assay. HCC was associated with marked transcriptional deregulation of hundreds of protein-coding genes. In the partially resected livers, diminished transcriptional activity was observed in genes associated with drug catabolism and increased expression in genes related to inflammatory responses and cell proliferation. Moreover, several long noncoding RNAs and microRNAs not previously linked with HCC were found to be deregulated. In liver transplant recipients, down-regulation of genes involved in energy production and up-regulation of genes associated with glycolysis were detected. Numerous copy number variants events were observed, with hotspots on chromosomes 1 and 17. Amplifications were more common than deletions and spanned regions containing genes potentially involved in tumorigenesis. Colony stimulating factor 1 receptor (CSF1R), fibroblast growth factor receptor 3 (FGFR3), fms-like tyrosine kinase 3 (FLT3), nucleolar phosphoprotein B23 (NPM1), platelet-derived growth factor receptor alpha polypeptide (PDGFRA), phosphatase and tensin homolog (PTEN), G-protein-coupled receptors-like receptor Smoothened (SMO), and tumor protein P53 (TP53) were mutated in all tumors; another 26 cancer-related genes were mutated with variable penetrance. Conclusion: Our results underscore the marked molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are needed for management of individual HCC. These data will serve as a resource to generate hypotheses for further research to improve our understanding of HCC biology. (Hepatology Communications 2018; 00:000-000).


The comparison of three different molecular imaging methods in localization and grading of insulinoma.
This cross-sectional study compared the value of molecular imaging (Exendin-4 positron emission tomography/computed tomography [PET/CT], 68Ga-DOTATATE PET/CT, 18F- fluorodeoxyglucose [FDG] PET/CT) in insulinoma localization by stratified tumor size and grading, and explored the correlation of the related the maximum standardized uptake value (SUVmax) with insulinoma grading, Ki-67, maximum tumor diameter, and glucose metabolism. In 28 insulinoma patients, the sensitivity of three types of PET/CT for localizing insulinoma was calculated according to tumor size and grade. We compared the SUVmax for different insulinoma grades and analyzed the correlation of SUVmax with Ki-67, maximum tumor diameter, and glucose metabolism indicators. The study included 12 grade (G) 1 and 16 G2 cases, with maximum tumor diameters ranging from 9 to 40 mm. Without differentiation by size and grade, the sensitivity of Exendin-4 PET/CT to localize insulinoma was 100%, which significantly exceeded that of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT (75% and 57%, respectively). In tumors with a maximum diameter ≤ 20 mm and ≤ 15 mm, the sensitivity of Exendin-4 (both 100%) significantly exceeded that of 68Ga-DOTATATE PET/CT (74% and 64%, respectively) and 18F-FDG PET/CT (54% and 50%, respectively). In G1 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of 18F-FDG PET/CT, but not that of 68Ga-DOTATATE PET/CT, while in G2 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of both other types. However, all three PET/CT types missed a metastatic lymph node in one patient. The 18F-FDG PET/CT SUVmax was significantly lower than that of the other PET/CT types and that of 68Ga-DOTATATE PET/CT was significantly lower in G2 than in G1. 68Ga-DOTATATE PET/CT SUVmax correlated negatively with Ki-67. A receiver operating characteristic (ROC) curve suggested that 68Ga-DOTATATE PET/CT SUVmax > 19.9 could predict G1 tumors. Exendin-4 PET/CT was superior to 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT for insulinoma localization, particularly small and G2 tumors, but its diagnostic value in small metastatic lymph nodes requires further exploration. 68Ga-DOTATATE PET/CT SUVmax could be used as an adjunct to pathology, and a value > 19.9 could predict G1 tumors. No PET/CT SUVmax could predict tumor maximum diameter and glucose metabolism.


Estrogen implants in the medial preoptic area stimulate maternal behavior in male rats.
The present study investigated whether the medial preoptic area (MPOA) mediates estrogen stimulation of maternal behavior in the male as it does in the female. Previous studies have shown that lesions of the medial preoptic area prevent sensitization of maternal behavior in male rats and that in gonadectomized, hormonally primed males, systemically administered estradiol benzoate stimulates short-latency maternal behavior. These findings are similar to those found in females. In the present study adult males were gonadectomized and hormonally primed with subcutaneously implanted capsules of estradiol (Days 1-16) and progesterone (Days 3-15) and then were stereotaxically implanted bilaterally in the MPOA with implants containing 10% estradiol. Tests with young pups were started 48 h later and continued for 10 days (11 tests). Control groups were implanted in the MPOA with cholesterol or were injected subcutaneously with estradiol benzoate (100 microg/kg). Estradiol implanted males had shorter latencies for maternal behavior (retrieving, crouching, licking pups) than cholesterol implanted males, but their latencies were slightly longer than those of estradiol benzoate injected males. The medial preoptic area, therefore, mediates estrogen stimulation of maternal behavior in males as it does in females.


Rapid intracellular TEA block of the KcsA potassium channel.
Intracellular tetraethylammonium (TEA) inhibition was studied at the single-channel level in the KcsA potassium channel reconstituted in planar lipid bilayers. TEA acts as a fast blocker (resulting in decreased current amplitude) with an affinity in the 75 mM range even at high bandwidth. Studies over a wide voltage range reveal that TEA block has a complex voltage-dependence that also depends on the ionic conditions. These observations are examined in the context of permeation models to extend our understanding of the coupling between permeant ions and TEA blockade.


Reduced repeat length of nascent nucleosomal DNA is generated by replicating chromatin in vivo.
Micrococcal nuclease digestion of nuclei from sea urchin embryos revealed transient changes in chromatin structure which resulted in a reduction in the repeat length of nascent chromatin DNA as compared with bulk DNA. This was considered to be entirely the consequence of in vivo events at the replication fork (Cell 14, 259, 1978). However, a micrococcal nuclease-generated sliding of nucleosome cores relative to nascent DNA, which might account for the smaller DNA fragments, was not excluded. In vivo [3H]thymidine pulse-labeled nuclei were fixed with a formaldehyde prior to micrococcal nuclease digestion. This linked chromatin proteins to DNA and thus prevented any in vitro sliding of histone cores. All the nascent DNAs exhibiting shorter repeat lengths after micrococcal nuclease digestion, were resolved at identical mobilities in polyacrylamide gels of DNA from fixed and unfixed nuclei. We conclude that these differences in repeat lengths between nascent and bulk DNA was generated in vivo by changes in chromatin structure during replication, rather than by micrococcal nuclease-induced sliding of histone cores in vitro.


[Bacterial ClpX protease structure and function--a review].
ClpX is a member of Hsp100 (heat-shock protein) family which is conserved among organisms. Hsp100/ Clp implicates in stress resistance, intracellular protein turn-over, DNA replication and regulation of gene expression. Tuberculosis remains one of the major threats to human health. In pathogens, ClpX protease plays an important role in the gene expression regulation, pathogenesis, and resistance of immune stress. The structure, substrates and target genes of ClpX are summarized in this study. The biological function of M. tuberculosis ClpX, such as gene expression regulation, pathogenesis, intracellular survival and persistence, evolution and structural feature, substrates is the focus of this summary.


Quantum Dot Sensitized Photoelectrodes.
Quantum Dots (QDs) are promising alternatives to organic dyes as sensitisers for photocatalytic electrodes. This review article provides an overview of the current state of the art in this area. More specifically, different types of QDs with a special focus on heavy-metal free QDs and the methods for preparation and adsorption onto metal oxide electrodes (especially titania and zinc oxide) are discussed. Eventually, the key areas of necessary improvements are identified and assessed.


Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.
The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.


Jet set pets: examining the zoonosis risk in animal import and travel across the European Union.
Ownership of companion animals or pets is popular throughout the world. Unfortunately, such animals are susceptible to and potential reservoirs of zoonotic pathogens. Close proximity to and contact with pets can lead to human infections. The distribution of zoonotic diseases associated with companion animals such as dogs and cats is not uniform around the world, and moving animals between regions, countries, and continents carries with it the risk of relocating the pathogens they might harbor. Critical among these zoonotic diseases are rabies, echinococcosis, and leishmania. In addition, the protozoan parasites, Toxoplasma gondii and Giardia duodenalis, are also significant agents for human disease of pet origin. Considerable effort is applied to controlling movements of companion animals, particularly dogs, into the European Union. However, free movement of people and their pets within the European Union is a risk factor for the translocation of diseases and their vectors. This review considers the current distribution of some of these diseases, the risks associated with pet travel, and the controls implemented within Europe to prevent the free movement of zoonotic pathogens.


Production of Aspergillus niger biomass on sugarcane distillery wastewater: physiological aspects and potential for biodiesel production.
Sugarcane distillery waste water (SDW) or vinasse is the residual liquid waste generated during sugarcane molasses fermentation and alcohol distillation. Worldwide, this effluent is responsible for serious environmental issues. In Reunion Island, between 100 and 200 thousand tons of SDW are produced each year by the three local distilleries. In this study, the potential of Aspergillus niger to reduce the pollution load of SDW and to produce interesting metabolites has been investigated. The fungal biomass yield was 35 g L-1 corresponding to a yield of 0.47 g of biomass/g of vinasse without nutrient complementation. Analysis of sugar consumption indicated that mono-carbohydrates were initially released from residual polysaccharides and then gradually consumed until complete exhaustion. The high biomass yield likely arises from polysaccharides that are hydrolysed prior to be assimilated as monosaccharides and from organic acids and other complex compounds that provided additional C-sources for growth. Comparison of the size exclusion chromatography profiles of raw and pre-treated vinasse confirmed the conversion of humic- and/or phenolic-like molecules into protein-like metabolites. As a consequence, chemical oxygen demand of vinasse decreased by 53%. Interestingly, analysis of intracellular lipids of the biomass revealed high content in oleic acid and physical properties relevant for biodiesel application. The soft-rot fungus A. niger demonstrated a great ability to grow on vinasse and to degrade this complex and hostile medium. The high biomass production is accompanied by a utilization of carbon sources like residual carbohydrates, organic acids and more complex molecules such as melanoidins. We also showed that intracellular lipids from fungal biomass can efficiently be exploited into biodiesel.


Guanylyl cyclases, nitric oxide, natriuretic peptides, and airway smooth muscle function.
Airway smooth muscle (ASM) plays an important role in asthma pathophysiology through its contractile and proliferative functions. The cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) are second messengers capable of mediating the effects of a variety of drugs and hormones. There is a large body of evidence to support the hypothesis that cAMP is a mediator of the ASM's relaxant effects of drugs, such as beta2-adrenoceptor agonists, in human airways. Although most attention has been paid to this second messenger and the signal transduction pathways it activates, recent evidence suggests that cGMP is also an important second messenger in ASM with important relaxant and antiproliferative effects. Here, we review the regulation and function of cGMP in ASM and discuss the implications for asthma pathophysiology and therapeutics. Recent studies suggest that activators of soluble and particulate guanylyl cyclases, such as nitric oxide donors and natriuretic peptides, have both relaxant and antiproliferative effects that are mediated through cGMP-dependent and cGMP-independent pathways. Abnormalities in these pathways may contribute to asthma pathophysiology, and therapeutic manipulation may complement the effects of beta2-adrenoceptor agonists.


A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome.
Several mutations have been described in the human androgen receptor gene including constitutional mutations in androgen insensitivity syndrome, somatic mutations in prostate cancer and triplet expansions in Kennedy's disease (Gottlieb et al. 1997). Here we report on two siblings with complete androgen insensitivity and a novel missense mutation, D695V, in their androgen receptor gene. The two XY females are siblings of German descent and presented at the ages of 23 and 19 years, respectively, with typical clinical features of complete androgen insensitivity. We found both siblings to be hemizygous for a new adenine to thymine transversion at the second nucleotide of codon 695 within the fourth exon of the human androgen receptor gene. The resulting missense mutation D695V is located at the amino-terminal border of the ligand-binding domain of the androgen receptor. The aspartic acid residue at this position is highly conserved in the steroid binding domains of other members of the nuclear receptor family and has already been found to be the site of two other missense mutations associated with androgen insensitivity syndrome (Ris Stalpers et al. 1991, Hiort et al. 1996). Three of four reported subjects showed the complete androgen insensitivity phenotype, in accordance with the two siblings in our study. We suggest that the existence of three pathological amino acid substitutions for aspartic acid 695 most likely reflects the essential role of this residue for normal androgen receptor function in male sexual differentiation.


Restenosis in Hemodialytic Fistulas and Chronic Kidney Disease-Associated Vascular Disease: Two Pathologies Driven by Metakaryotic Stem Cells.
Chronic kidney disease (CKD) exacerbating vascular disease poses a major challenge to nephrology. Surgically placed vascular fistulas, as an aid to hemodialysis prior to kidney transplant, have extended many lives, while post-surgical restenosis closure of the fistula by smooth muscle cells affects many lives. When post-surgical restenosis is developed, palliative measures are almost always surgical: there are no effective drug treatments. In this study, we offer a testable hypothesis that effects of CKD on widely distributed vascular diseases and the phenomenon of fistula restenosis are both driven by the pathologic creation of non-dividing smooth muscle cells via asymmetric division of exponentially increasing metakaryotic stem cells. In slow growing atherosclerotic plaques, the Benditts demonstrated clonality of smooth muscle cells that we posit originate in a single mutated metakaryotic stem cell of fetal/juvenile vasculogenesis. In the fast process of fistula restenosis, we posit quiescent metakaryotic stem cells "on call" for wound healing among which are rare stem cells that have lost the ability to cease division. These hypotheses and suggestions for specific research paths toward development of effective drug therapies are built on (a) our shared discoveries of the role of metakaryotic stem cells in organogenesis, carcinogenesis, and atherosclerotic plaque formation and (b) the recent finding that metakaryotic cancer stem cells are constitutively resistant to radio- and chemotherapies yet sensitive to killing by a wide range of existing drugs. We propose to test these hypotheses in discarded fistulas and stem cells derived therefrom, and, if supported, to test drug-eluting devices to block fistula restenosis.


Postoperative maxillary cyst: a case report.
Postoperative maxillary cyst is a quite rare delayed complication of surgical intervention associated with maxillary sinuses. It occurs many years after surgery. This paper describes a 54-year-old woman presenting with swelling of left cheek for seven-years duration. The orthopantomograph revealed a unilocular cystic radiolucency with well-defined margins in left maxillary sinus. In the computerized tomography, the cyst had a sclerotic wall with bony condensations. Aspiration cytology revealed many neutrophil leukocytes. Cyst was drained and enucleated. Histopathologically, it had a fibrous wall with inflammation and focal reactive bone formation and lined by a respiratory-type epithelium. In the clinical history, it is learned that she had a maxillary sinus surgery 8 years ago and the diagnosis was made considering the clinical and histopathological findings.


Hole Transport Layer Free Perovskite Light-Emitting Diodes With High-Brightness and Air-Stability Based on Solution-Processed CsPbBr3-Cs4PbBr6 Composites Films.
Recently, perovskite light-emitting diodes (PeLEDs) have drew widespread attention due to their high efficiencies. However, because of the sensitivity to moisture and oxygen, perovskite luminescent layers are usually prepared in high-purity nitrogen environment, which increases the cost and process complexity of device preparation and seriously hindrances its commercialization of PeLED in lighting and display application. Herein, dual-phase all-inorganic composite CsPbBr3-Cs4PbBr6 films are fabricated from CsBr-rich perovskite solutions by a simple one-step spin-coating method in the air with high humidity. Compared with the pure CsPbBr3 film, the composite CsPbBr3-Cs4PbBr6 film has much stronger photoluminescence emission and longer fluorescence lifetime, accompanied by increased photoluminescence quantum yield (33%). As a result, we obtained green PeLED devices without hole transport layer exhibiting a maximum brightness of 72,082 cd/m2 and a maximum external quantum efficiency of about 2.45%, respectively. More importantly, the champion device shows excellent stability with operational half-lifetime exceeding 1,000 min under continuous operation in the air. The dual-phase all-inorganic composite CsPbBr3-Cs4PbBr6 film shows attractive prospect for advanced light emission applications.


Effect of denture cleansers on the color stability of heat cure acrylic resin.
To compare the color stability of heat cure acrylic resin after immersion in distilled water and denture cleansers. In-vitro experimental study. Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences and Al-Karam Textiles, Karachi, from January to April 2012. Seventy two rectangular shaped specimens; 18 specimens were measured at baseline (control group) of the study (0 day), 18 specimens were immersed in distilled water. Eighteen (18) in Fittydent denture cleanser tablets for 10 minutes and eighteen (18) in Dentipur denture cleanser tablets for 10 minutes. Specimens were polished and stored in istilled water for 24 hours prior to experiment. After 60 days of immersion, the specimens were tested for color changes with spectrophotometer. SPSS 16 was used for statistical analysis. There was statistically significant difference in the color change (ΔE) among all groups (p < 0.001) after 60 days of immersion. At baseline (0 day), trace amount of color change was observed whereas when specimens were immersed in Fittydent denture cleansers tablets for 60 days noticeable change in color was observed. Very slight change in color was bserved when specimens were immersed in distilled water and dentipur denture cleanser solution. The color stability of denture base acrylic resin was influenced by the type of denture cleansers used.


Radiosensitizing effects of nicotinamide on a C3H mouse mammary adenocarcinoma. A study on per os drug administration.
Nicotinamide is an inhibitor of adenosine diphosphate ribosyl transferase (ADPRT) which is involved in the mechanism of DNA repair after high doses of ionizing radiation. C3H mice with transplanted mammary adenocarcinomas were treated with low doses of nicotinamide, 10 mg/kg, 5 days a week, and in combination with ionizing radiation, 30 Gy, using different drug dose schedules. Mice given nicotinamide in combination with irradiation took a longer time to reach a tumor volume of 1,000 mm3 and a higher complete response rate (i.e. defined as total disappearance of the tumor for at least 7 days) than those given radiation alone. This was true whether nicotinamide was given daily from one week before tumor transplantation until the animal was killed or from transplantation day until day of irradiation. In addition, nicotinamide given per os at a dose between the recommended maximum daily allowance for human subjects (20 mg/70 kg), and the therapeutic allowance (1 g-12 g daily) 5 days a week for 9 weeks, showed a radiosensitizing effect without any histologically detectable damage to the normal tissues of the mouse, including bone marrow, intestine and the liver.


Survival curve estimation for informatively coarsened discrete event-time data.
Interval-censored, or more generally, coarsened event-time data arise when study participants are observed at irregular time periods and experience the event of interest in between study observations. Such data are often analysed assuming non-informative censoring, which can produce biased results if the assumption is wrong. This paper extends the standard approach for estimating survivor functions to allow informatively interval-censored data by incorporating various assumptions about the censoring mechanism into the model. We include a Bayesian extension in which final estimates are produced by mixing over a distribution of assumed censoring mechanisms. We illustrate these methods with a natural history study of HIV-infected individuals using assumptions elicited from an AIDS expert.


Seasonal variations of Vibrio cholerae (non-O1) isolated from California coastal waters.
This report compares recovery of non-O1 Vibrio cholerae strains from seven California coastal sites during the winter and summer of 1983. A total of 41 identified and 27 presumptive nn-O1 V. cholerae strains were recovered from six of seven coastal sites in the summer. A 5-to 56-fold increase in the numbers of organisms isolated from different sites occurred in the summer months, when water temperatures were 1.9 to 5.1 degrees C higher. At the three sites where the highest levels of non-O1 V. cholerae were found, pollution, as measured by the total number of coliforms, exceeded the legal limit (less than 1,000 coliforms per 100 ml.).


Cryopreservation of a threatened medicinal plant, Valeriana jatamansi Jones, using vitrification and assessment of biosynthetic stability of regenerants.
Valeriana jatamansi Jones is a medicinal plant of the Himalayan region with high trade value. Since overexploitation of this wild species led it to be listed as threatened, a comprehensive conservation strategy is needed. Cryopreservation would be a useful complementary method to conventional conservation methods. To develop a cryopreservation protocol for V. jatamansi with maintenance of biosynthetic stability of regenerants. In vitro shoot tips were cryopreserved using vitrification with either PVS2 or PVS3 and the efficacy of the two cryoprotectant mixtures compared. Regenerated plantlets were evaluated by HPLC analysis for contents of four valepotriates viz. valtrate, acevaltrate, didrovaltrate and IVHD valtrate. The highest shoot recovery (91.6%) after transfer to liquid nitrogen was obtained when shoot tips were treated with PVS2 at 0°C for 110 min, which was significantly higher than the highest recovery (73.3%) obtained using PVS3 for any duration tested. Evaluation of biosynthetic stability showed no variation in valepotriate contents between in vitro maintained and cryopreserved derived plantlets. This protocol will be useful for the long-term conservation of this species as high frequency recovery and biosynthetic stability after cryopreservation were obtained.


Facilitating the performance of qNMR analysis using automated quantification and results verification.
Quantitative nuclear magnetic resonance (qNMR) is considered as a powerful tool for measuring the absolute amount of small molecules in complex mixtures. However, verification of the accuracy of such quantification is not a trivial task. In particular, preprocessing and integration steps are challenging and potentially erroneous. A script was developed in Matlab environment to automate qNMR analysis. Verification of the results is based on two evolving integration profiles. The analysis of binary mixtures of internal standards as well as pharmaceutical products has shown that all common artifacts (phase and baseline distortion, impurities) can be easily recognized in routine qNMR experiments. In the absence of distortion, deviation between automatically (mean value of several integrals) and manually calculated values was generally below 0.1%. The routine is independent of multiplet pattern, solvent, spectrometer, nuclei type and pulse sequence used. In general, the usage of the developed script can facilitate and verify results of routine qNMR analysis in an automatic manner. Copyright © 2017 John Wiley & Sons, Ltd.


Percutaneous transhepatic cholecystostomy: effective treatment of acute cholecystitis in high risk patients.
The mortality rate for cholecystectomy for acute cholecystitis in the elderly is 10% in low risk patients and increases threefold in high risk patients. Ultrasound-guided percutaneous transhepatic cholecystostomy may serve as a rapid and relatively safe tool to relieve symptoms of sepsis and decrease gallbladder distension. To determine the safety and effectiveness of PTC in the treatment of acute cholecystitis in elderly debilitated high risk patients. The study sample included 10 patients aged 63-88 (mean 77.6 years) with clinical and sonographic signs of acute cholecystitis for more than 48 hours (fever, white blood cells > 12,000/mm, positive Murphy sign and distended gallbladder) who underwent ultrasound guided PTC. All had severe underlying disease (coronary heart disease, renal failure, chronic obstructive pulmonary disease, and others) that places them at high risk for surgical intervention. Eight patients showed rapid regression of the clinical symptoms following PTC drainage. One patient with bacterial endocarditis was febrile for 5 days after catheter insertion, but with rapid resolution of the biliary colic and sepsis. One patient died from perforation of the gallbladder and small bowel. PTC catheters were withdrawn 3-25 days after the procedure and the patients remained free of biliary symptoms. Two patients underwent successful elective cholecystectomy 3 weeks later. PTC may be a safe and effective treatment for high risk elderly patients with acute cholecystitis. It can be followed by elective cholecystectomy if the underlying condition improves, as soon as the patient stabilizes and no sepsis is present, or by conservative management in high surgical-risk patients.


The importance of being knotted: effects of the C-terminal knot structure on enzymatic and mechanical properties of bovine carbonic anhydrase II.
In order to better understand the contribution of the knotted folding pattern to the enzymatic and mechanical properties of carbonic anhydrases, we replaced Gln-253 of bovine carbonic anhydrase II with Cys, which allowed us to measure the mechanical strength of the protein against tensile deformation by avoiding knot tightening. The expressed protein, to our surprise, turned out to contain two conformational isomers, one capable of binding an enzymatic inhibitor and the other not, which led to their separation through affinity chromatography. In near- and far-UV circular dichroism and fluorescence spectra, the separated conformers were very similar to each other and to the wild-type enzyme, indicating that they both had native-like conformations. We describe new evidence which supports the notion that the difference between the two conformers is likely to be related to the completeness of the C-terminal knot formation.


Draft Genome Sequence of Pseudoalteromonas sp. Strain ND6B, an Oil-Degrading Isolate from Eastern Mediterranean Sea Water Collected at a Depth of 1,210 Meters.
Here, we report the draft genome of Pseudoalteromonas sp. strain ND6B, which is able to grow with crude oil as a carbon source. Strain ND6B was isolated from eastern Mediterranean Sea deep water at a depth of 1,210 m. The genome of strain ND6B provides insight into the oil-degrading ability of the Pseudoalteromonas species.


Pediatric Tibial Osteomyelitis.
Osteomyelitis shows a strong predilection for the tibia in the pediatric population and is a significant source of complications. The purpose of this article is to retrospectively review a large series of pediatric patients with tibial osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid diagnosis and/or improve treatment outcomes. A 10-year retrospective review was performed of clinical records of all cases of pediatric tibial osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. One hundred ninety-one patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 5.7 days. Less than 40% of patients had a recent episode of trauma. Almost 60% of patients could not bear weight on admission. Over 40% of patients had a temperature above 38°C. Erythrocyte sedimentation rate was elevated in 78% and the C-reactive protein was elevated in 90% of patients. In total, 42% of blood cultures and almost 75% of tissue cultures were positive, with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 43% of patients had surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. Six postsurgical complications and 46 readmissions were noted: 25 for relapse, with the remainder due to social and antibiotic-associated complications. Although generally diagnosed on presentation, pediatric tibial osteomyelitis can require more sophisticated investigations and prolonged management. Treatment with intravenous and oral antibiotics and surgical debridement where indicated can lead to a good clinical outcome, although complications are often noted. Level IV-Prognostic study.


Circular dichroism studies of imide derivatives of amines.
Circular dichroism curves have been measured for phthaloyl-, maleyl- and itaconyl-derivatives of a number of amines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or cyclohexyl-groups) and of 1,2,3,4-tetrahydro-1-naphthylamine and 1,2,3,4-tetrahydro-2-naphthylamine. We conclude that the determination of absolute configuration of amines examined can be made on the basis of C.D. curves of their phthaloyl-, maleyl- and itaconyl-derivatives, referring to that portion of the curve relating to the imide chromophore absorption.


Fosfomycin Biosynthesis via Transient Cytidylylation of 2-Hydroxyethylphosphonate by the Bifunctional Fom1 Enzyme.
Fosfomycin is a wide-spectrum phosphonate antibiotic that is used clinically to treat cystitis, tympanitis, etc. Its biosynthesis starts with the formation of a carbon-phosphorus bond catalyzed by the phosphoenolpyruvate phosphomutase Fom1. We identified an additional cytidylyltransferase (CyTase) domain at the Fom1 N-terminus in addition to the phosphoenolpyruvate phosphomutase domain at the Fom1 C-terminus. Here, we demonstrate that Fom1 is bifunctional and that the Fom1 CyTase domain catalyzes the cytidylylation of the 2-hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-HEP. On the basis of this new function of Fom1, we propose a revised fosfomycin biosynthetic pathway that involves the transient CMP-conjugated intermediate. The identification of a biosynthetic mechanism via such transient cytidylylation of a biosynthetic intermediate fundamentally advances the understanding of phosphonate biosynthesis in nature. The crystal structure of the cytidylyl-HEP-bound CyTase domain provides a basis for the substrate specificity and reveals unique catalytic elements not found in other members of the CyTase family.


Dissecting the energetics of a protein-protein interaction: the binding of ovomucoid third domain to elastase.
An understanding of the structural basis for protein-protein interactions, and molecular recognition in general, requires complete characterization of binding energetics. Not only does this include quantification of the changes that occur in all of the thermodynamic parameters upon binding, including the enthalpy, entropy and heat capacity, but a description of how these changes are modulated by environmental conditions, most notably pH. Here, we have investigated the binding of turkey ovomucoid third domain (OMTKY3), a potent serine protease inhibitor, to the serine protease porcine pancreatic elastase (PPE) using isothermal titration calorimetry and structure-based thermodynamic calculations. We find that near neutral pH the binding energetics are influenced by a shift in the pKa of an ionizable group, most likely histidine 57 in the protease active site. Consequently, the observed binding energetics are strongly dependent upon solution conditions. Through a global analysis, the intrinsic energetics of binding have been determined, as have those associated with the pKa shift. The protonation energetics suggest that the drop in pKa is largely due to desolvation of the histidine residue. The resulting deprotonation is necessary for the enzymatic function of elastase. Intrinsically, at 25 degrees C the binding of OMTKY3 to PPE is characterized by an almost negligible enthalpy change, a large positive entropy change, and a large negative heat capacity change. These parameters are consistent with a model of the OMTKY3-PPE complex, which shows a large and significantly apolar protein-protein interface. Thermodynamic calculations based upon changes that occur in polar and apolar solvent-accessible surface area are in very good agreement with the measured intrinsic binding energetics.


The effect of bilateral intrapleural infusion of lidocaine with fentanyl versus only lidocaine in relieving pain after coronary artery bypasses surgery.
Pain control during surgery in order to cause analgesia and reduce the somatic and autonomic response may decrease the morbidity. Intrapleural catheter embedding during surgery under direct vision of surgeon is safe and easy and without potential risk of thoracic epidural block. The aim of this study was to investigate the effect of bilateral intrapleural infusion of lidocaine with fentanyl versus only lidocaine in relieving pain after coronary artery bypass surgery. In this prospective randomized double blind clinical trial,130 adult patients undergoing elective CABG with age range of 20 to 60 years were divided into two groups receiving either lidocaine and fentanyl (group A) or lidocaine (group B). The analgesia was evaluated every two hours in all intubated and non-intubated patients using Visual analog scale (VAS) and data were analyzed using SPSS software package. Of all patients, 67 (51.5%) were males and 63 (48.5%) were females. The average age of subjects was 53.49 ± 5.099 years. Mean pain score six hours after the surgery was statistically different between the groups at all times. The pain in patients receiving combination of lidocaine and fentanyl is less than patients receiving only lidocaine.


Effects of a specific blend of essential oils on apparent nutrient digestion, rumen fermentation and rumen microbial populations in sheep fed a 50:50 alfalfa hay:concentrate diet.
An experiment was conducted to investigate the effects of a specific mixture of essential oils (MEO), containing thyme, clove and cinnamon EO, on rumen microbial fermentation, nutrient apparent digestibility and blood metabolites in fistulated sheep. Six sheep fitted with ruminal fistulas were used in a repeated measurement design with two 24-d periods to investigate the effect of adding MEO at 0 (control), 0.8, and 1.6 mL/d on apparent nutrient digestibility, rumen fermentation characteristics, rumen microbial population and blood chemical metabolites. Animals were fed with a 50:50 alfalfa hay:concentrate diet. Ruminal pH, total volatile fatty acids (VFA) concentration, molar proportion of individual VFA, acetate: propionate ratio and methane production were not affected with MEO. Relative to the control, Small peptides plus amino acid nitrogen and large peptides nitrogen concentration in rumen fluid were not affected with MEO supplementation; while, rumen fluid ammonia nitrogen concentration at 0 and 6 h after morning feeding in sheep fed with 1.6 mL/d of MEO was lower (p<0.05) compared to the control and 0.8 mL/d of MEO. At 0 h after morning feeding, ammonia nitrogen concentration was higher (p<0.05) in sheep fed 0.8 mL/d of MEO relative to 1.6 mL/d and control diet. Ruminal protozoa and hyper ammonia producing (HAP) bacteria counts were not affected by addition of MEO in the diet. Relative to the control, no changes were observed in the red and white blood cells, hemoglobin, hematocrit, glucose, beta-hydroxybutyric acid, cholesterol, total protein, albumin, blood urea nitrogen and aspartate aminotransferase and alanine aminotransferase concentration. Apparent total tract digestibility of dry matter, crude proten, organic matter, and neutral detergent fiber were not influenced by MEO supplementation. The results of the present study suggested that supplementation of MEO may have limited effects on apparent nutrient digestibility, ruminal fermentation and protozoa and HAP bacteria count, blood cells and metabolites.


Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response.
Proanthocyanidins (PACs) are plant-derived, multifunctional compounds that possess high interactivity with extracellular matrix (ECM) components. The documented affinity of PACs for type-I collagen is directly correlated with their structural features and degree of polymerization. In this investigation, centrifugal partition chromatography (CPC) was used to sequentially deplete less active monomeric and polymeric PACs from a crude Pinus massoniana bark extract to create refined mixtures enriched in oligomeric PACs. The ability of these oligomeric PACs to modify the mechanical properties of the dentin collagen matrix and their biocompatibility with dental pulp cells (DPCs) was evaluated in an innovative biomimetic environment. The refined mixtures displayed high interactivity with dentin collagen as demonstrated by a significant increase (>5-fold) in the modulus of elasticity of the dentin matrix. In a simplified model of the dentin-DPC complex, DPCs embedded within their native ECM in the presence of PAC-treated dentin exhibited increased proliferation. Quantitative gene expression analyses indicated that exposure to PAC-treated dentin increased the expression of key biomineralization and odontogenic differentiation regulators, including RUNX2, BMP2, OCN, and DSPP. LC-MS/MS analysis revealed that PACs two to four units long (dimers, trimers, and tetramers) were being released from dentin into media, influencing cell behavior. Overall, the results suggested that PAC dimers, trimers, and tetramers are not only biocompatible, but enhance the differentiation of DPCs towards a phenotype that favors biomineralization. PAC-enriched refined mixtures can influence the field of biomaterials and regeneration by serving as renewable, non-cytotoxic agents that can increase the mechanical properties of biomaterials. Pine bark extract is a renewable source of structurally diverse proanthocyanidins (PACs), multifunctional compounds whose interaction with collagen can be tailored to specific purposes by enrichment of selected PACs from the complex mixture. Oligomeric PACs were enriched from the extract and were shown here to sustain desired tissue modification and were thus assessed for cellular response in a model of the dentin-pulp interface. This model was developed to mimic leaching of potentially reactive compounds into pulp tissue. Dental pulp cells exposed to PAC-treated dentin showed increased proliferation and expression of genes necessary for extracellular matrix deposition and biomineralization, processes crucial for forming new dentin. Thus, collagen-interactive PACs may also enhance tissue regeneration and have broad impact in tissue engineering.


Monoclonal antibodies against the free subunits of human chorionic gonadotrophin.
Discordant results on body fluid levels of human chorionic gonadotrophin (hCG) free alpha- and beta-subunits under physiological and pathophysiological conditions, prompted us to raise a total of 260 monoclonal antibodies (MCA) against free hCG-alpha, free hCG-beta, holo-hCG, human follicle-stimulating hormone and bovine luteinizing hormone; 153 MCA recognizing the human alpha-subunit and 28 reacting with hCG-beta were extensively analysed for their intra- and inter-species cross-reactivity with homologous hormones, and for the compatibility of epitopes recognized by them. The immunological topography of free hCG-alpha and free hCG-beta was resolved by these MCA, and epitope maps were designed. Six antigenic determinants on the free alpha-chain (alpha 1-alpha 6), clustered in three spatially distinct domains, and seven epitopes on the surface of free hCG-beta (beta 1-beta 7), could be distinguished. Strikingly, three alpha-chain epitopes (alpha 4, alpha 5 and alpha 6) were shared between various species, which is in contradiction to the concept of immunological species-specificity of alpha-subunits. Three determinants were found to be present only on the free subunits but not on holo-hCG (alpha 6, beta 6 and beta 7), and only two determinants (beta 1 and beta 7) were hormone-specific for hCG. Based on this information, an immunoenzymometric assay for the free alpha-subunit of human glycoprotein hormones was established, with a sensitivity of 1.3 pg/well and a cross-reactivity with holo-hCG of less than 0.005%.(ABSTRACT TRUNCATED AT 250 WORDS)


A Game-Based Repeated Assessment for Cognitive Monitoring: Initial Usability and Adherence Study in a Summer Camp Setting.
The current feasibility study examined the adherence, reliability, and assessment potential of an evidence-based game-like mobile Monitoring Tool (Akili Interactive Labs), to monitor 100 participants' cognition for eight sessions at a summer camp for children with special needs. A validated measure of attention was administered at baseline. In the last session, participants completed an exit questionnaire. The Monitoring Tool was found to be enjoyable, and showed a high rate of adherence. No Monitor-related adverse events were reported. Monitor metrics showed good reliability across repeated measurements, indicating it is stable over long-term cognitive monitoring. There was evidence that the Monitoring Tool was able to detect differences in cognition between the children diagnosed with attention deficit hyperactivity disorder and autism spectrum disorders.


Fragile spectral and temporal auditory processing in adolescents with autism spectrum disorder and early language delay.
We investigated low-level auditory spectral and temporal processing in adolescents with autism spectrum disorder (ASD) and early language delay compared to matched typically developing controls. Auditory measures were designed to target right versus left auditory cortex processing (i.e. frequency discrimination and slow amplitude modulation (AM) detection versus gap-in-noise detection and faster AM detection), and to pinpoint the task and stimulus characteristics underlying putative superior spectral processing in ASD. We observed impaired frequency discrimination in the ASD group and suggestive evidence of poorer temporal resolution as indexed by gap-in-noise detection thresholds. These findings question the evidence of enhanced spectral sensitivity in ASD and do not support the hypothesis of superior right and inferior left hemispheric auditory processing in ASD.


Neurobiology a century ago at the Marine Biological Laboratory, Woods Hole.
Neurobiology was a central concern at the Marine Biological Laboratory (MBL), Woods Hole at the end of the last century, when the director Charles Otis Whitman set up a seminar for discussion of research and general issues in 'neurology', which took place annually from 1896 to 1900 and generated intense interest among MBL researchers. Although the emerging fields within neurobiology underwent changes, neurological concerns continued to play a central role. This article explores the activity at the MBL in the 1890s when the various studies had not yet unified to form the field of neurobiology.


Characteristics of general practitioner consultations prior to suicide: a nested case-control study in New Zealand.
To examine characteristics of general practice consultations in a New Zealand primary care population of patients who died by suicide. Case control study design, with data linkage between the RNZCGP Research Unit Database, the National Mortality Database and the Hospital Separation Diagnosis Database (hospital discharges) from 1996 to 2001. The cases were suicides who had attended a general practice contributing data to the Research Unit database. Each case was matched by gender and age to three randomly selected patients from the Research Unit database. There were 221 cases of suicide identified, of which 60% had a general practice consultation in the 6 months prior to death. The significant exposure variables, corrected OR (95% CI) in the multivariate analysis were: any previous hospital admission (between January 1996 and date of death) for a psychiatric condition, 23.75 (9.01 to 62.63); any notation in the general practice record of depression, suicidal ideation or self-harm, 14.97 (4.61 to 48.65); previous hospital admission with self-harm, 8.39 (1.73 to 40.65); and general practice prescription of sedatives, 4.34 (1.69 to 11.10). In general, general practice patients who commit suicide have higher rates of depression, suicidal ideation, previous self harm, and sedative prescription than average.


Propensity score analysis the clinical characteristics of active distal and extensive ulcerative colitis: a retrospective study.
Background and Objectives: Ulcerative Colitis (UC) subtypes defined by disease extent and shared pathophysiology are important. Analyzing the clinical characteristics of UC with different disease extent and optimizing clinical typing are conducive to the pathogenesis research, disease monitoring and precise treatment. Methods: 188 patients with active UC were divided into distal and extensive colitis. The clinical characteristics of the two groups were analyzed by propensity score. Spearman is used for correlation analysis, and receiver operating characteristic (ROC) curve was used to evaluate the ability of clinical indicators to predict Mayo endoscopic subscore (MES). Results: Compared with distal colitis, extensive colitis had more severe disease activity, younger age, higher utilization rate of corticosteroids and incidence of extra intestinal manifestations (EIMs), and clinical indicators were differentially expressed in the two groups. After using propensity score, the incidence of EIMs in the extensive colitis was still higher than that in distal colitis. Inflammation, coagulation and immune indicators like CRP, FC, IL-10, D-D and α1-MG are higher in extensive colitis, and metabolic indicators like LDL-C, HDL-C, TC, GSP and albumin are higher in distal colitis. The correlation between clinical indicators and MES is affected by disease extent. The area under curve (AUC) of CRP + D-D + α2-MG for predicting distal colitis MES3 was 0.85, and the AUC of IL-6+ GSP+ α1-MG predicted extensive colitis MES3 can reach 0.82. Conclusion: Differential clinical indicators can become potential markers for predicting disease progression and prognosis, and have significance for UC mechanism research and drug development. We can select biomarkers according to lesion site.


Non-Malignant Cerebrospinal Fluid Ascites in a Patient with Atypical Teratoid Rhabdoid Tumor.
The development of symptomatic ascites from a ventriculoperitoneal shunt is rare in children without prior intra-abdominal pathology. Here we report a case of symptomatic ascites in a young child with a ventriculoperitoneal shunt and metastatic atypical teratoid rhabdoid tumor. This 15-month-old boy developed symptomatic ascites while undergoing chemotherapy for his malignant brain tumor. Diagnostic work up to identify the etiology of this ascites yielded a non-malignant, sterile transudate, refractory to repeated paracentesis. The ascites finally resolved with the conversion of the ventriculoperitoneal shunt to a ventriculoatrial shunt. This case report highlights the need to be suspicious of non-malignant cerebrospinal fluid ascites as a cause of peritoneal fluid accumulation even in children with malignant primary brain tumor. In this setting, conversion of the shunt from peritoneal to atrial drainage can rapidly alleviate the morbidity associated with this condition.


Quantification of long-term doxorubicin response dynamics in breast cancer cell lines to direct treatment schedules.
While acquired chemoresistance is recognized as a key challenge to treating many types of cancer, the dynamics with which drug sensitivity changes after exposure are poorly characterized. Most chemotherapeutic regimens call for repeated dosing at regular intervals, and if drug sensitivity changes on a similar time scale then the treatment interval could be optimized to improve treatment performance. Theoretical work suggests that such optimal schedules exist, but experimental confirmation has been obstructed by the difficulty of deconvolving the simultaneous processes of death, adaptation, and regrowth taking place in cancer cell populations. Here we present a method of optimizing drug schedules in vitro through iterative application of experimentally calibrated models, and demonstrate its ability to characterize dynamic changes in sensitivity to the chemotherapeutic doxorubicin in three breast cancer cell lines subjected to treatment schedules varying in concentration, interval between pulse treatments, and number of sequential pulse treatments. Cell populations are monitored longitudinally through automated imaging for 600-800 hours, and this data is used to calibrate a family of cancer growth models, each consisting of a system of ordinary differential equations, derived from the bi-exponential model which characterizes resistant and sensitive subpopulations. We identify a model incorporating both a period of growth arrest in surviving cells and a delay in the death of chemosensitive cells which outperforms the original bi-exponential growth model in Akaike Information Criterion based model selection, and use the calibrated model to quantify the performance of each drug schedule. We find that the inter-treatment interval is a key variable in determining the performance of sequential dosing schedules and identify an optimal retreatment time for each cell line which extends regrowth time by 40%-239%, demonstrating that the time scale of changes in chemosensitivity following doxorubicin exposure allows optimization of drug scheduling by varying this inter-treatment interval.


Dynamics of CN+alkane reactions by crossed-beam dc slice imaging.
The hydrogen atom abstraction reactions of CN (X (2)Sigma(+)) with alkanes have been studied using the crossed molecular beam technique with dc slice ion imaging at collision energies of 7.5 and 10.8 kcalmol. The product alkyl radical images were obtained via single photon ionization at 157 nm for the reactions of CN (X (2)Sigma(+)) with n-butane, n-pentane, n-hexane, and cyclohexane. From analysis of the images, we obtained the center-of-mass frame product angular distributions and translational energy distributions directly. The results indicate that the products are largely backscattered and that most of the available energy ( approximately 80%-85%) goes to the internal energy of the products. The reaction dynamics is discussed in light of recent kinetics data, theoretical calculations, and results for related halogen and oxygen atom reactions.


Disparities in oral anticoagulation initiation in patients with schizophrenia and atrial fibrillation: A nationwide cohort study.
Schizophrenia is associated with poor anticoagulation control and clinical prognosis in patients with atrial fibrillation (AF). Little is known about initiation of oral anticoagulation therapy (OAC) in this patient population. In the nationwide Danish health registries, we identified all patients with incident AF and schizophrenia with indication for OAC treatment. Patients with schizophrenia (n = 673) were matched 1:5 on sex, age, stroke risk score, and calendar-period to incident AF patients without schizophrenia. We calculated absolute risk and risk difference (RD) of OAC initiation, adjusting for stroke and bleeding risk factors. Analyses were stratified by calendar period (2000-2011 and 2012-2018) to account for changes after the introduction of non-vitamin K OACs (NOAC). Among patients with schizophrenia (mean age 69.5 years, 50.3% females), 33.7% initiated OAC within the first year after AF diagnosis, compared with 54.4% of patients without schizophrenia, corresponding to an adjusted RD of -20.7 (95% confidence interval [CI]: -24.7 to -16.7). OAC initiation increased over time regardless of schizophrenia status. During 2000-2011, 18.3% of patients with schizophrenia and 42.9% without schizophrenia initiated OAC (adjusted RD -23.6%, 95% CI -28.8 to -18.6). During 2012-2018, this was 48.5% and 65.7%, respectively (adjusted RD -14.4%, 95% CI -20.4 to -8.4). Initiation of OAC was substantially lower among patients with AF and schizophrenia compared with matched AF peers. These findings accentuate the importance of close attention to disparities in initiation of OAC treatment, and potential missed opportunities for prevention of disabling strokes in AF patients with schizophrenia.


[Effect of perioperative dexamethasone on nausea, vomiting and pain after total knee arthroplasty].
To investigate the effect of perioperative dexamethasone on nausea, vomiting and pain after unilateral total knee arthroplasty and to evaluate its safety. From February 2014 to June 2016, 100 patients with unilateral advanced osteoarthritis treated by total knee arthroplasty were divided into two groups: 50 patients in dexamethasone group including 27 males and 23 females, aged (72.30±7.02) years, were given intravenous drip of dexamethasone 10 mg before operation; 50 patients in saline group, including 26 males and 24 females, aged (71.30±6.08) years, were given the same amount of saline at the corresponding time. The VAS scores of pain at rest and at 45 degrees of knee flexion were recorded at 2, 4, 6, 8, 12, 24, 36 and 48 h after operation. Vomiting, antiemetic drugs and opioids were recorded at 0 to 24 h and 24 to 48 h after operation. The side effects and complications were recorded. All the 100 patients were followed up for an average of 14.5 months. VAS score of pain at rest in dexamethasone group was lower than that in saline group at 8, 24 and 48 h after operation (P<0.05); VAS score of dexamethasone group at 45 degrees after knee flexion was lower than that of saline group at 8 and 48 h after operation(P<0.05); VAS score of dexamethasone group at rest and 45 degrees after knee flexion was lower than that of saline group(P<0.05). The dosage of opioids and total opioids in dexamethasone group was lower than that in saline group at 0 to 24 h, 24 to 48 h after operation (P<0.05). The proportion of nausea and vomiting occurred at 0 to 24 h and 24 to 48 h after operation, and the proportion of antiemetic required at 0 to 24 h after operation had statistical significance between two groups(P<0.05). The total antiemetic dosage of dexamethasone group was less than that of saline group(P<0.05). As of the last follow-up, no complications such as infection, gastrointestinal ulcer and bleeding occurred in the two groups. Preoperative systemic application of dexamethasone can effectively reduce pain and nausea and vomiting after TKA without increasing postoperative complications.


Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors.
We compared changes in markers of muscle damage and systemic inflammation after submaximal and maximal lengthening muscle contractions of the elbow flexors. Using a cross-over design, 10 healthy young men not involved in resistance training completed a submaximal trial (10 sets of 60 lengthening contractions at 10% maximum isometric strength, 1 min rest between sets), followed by a maximal trial (10 sets of three lengthening contractions at 100% maximum isometric strength, 3 min rest between sets). Lengthening contractions were performed on an isokinetic dynamometer. Opposite arms were used for the submaximal and maximal trials, and the trials were separated by a minimum of two weeks. Blood was sampled before, immediately after, 1 h, 3 h, and 1-4 d after each trial. Total leukocyte and neutrophil numbers, and the serum concentration of soluble tumor necrosis factor-alpha receptor 1 were elevated after both trials (P < 0.01), but there were no differences between the trials. Serum IL-6 concentration was elevated 3 h after the submaximal contractions (P < 0.01). The concentrations of serum tumor necrosis factor-alpha, IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor and plasma C-reactive protein remained unchanged following both trials. Maximum isometric strength and range of motion decreased significantly (P < 0.001) after both trials, and were lower from 1-4 days after the maximal contractions compared to the submaximal contractions. Plasma myoglobin concentration and creatine kinase activity, muscle soreness and upper arm circumference all increased after both trials (P < 0.01), but were not significantly different between the trials. Therefore, there were no differences in markers of systemic inflammation, despite evidence of greater muscle damage following maximal versus submaximal lengthening contractions of the elbow flexors.


Comparative strengths and structural properties of the upper and lower cervical spine in flexion and extension.
The purpose of this study is to test the hypothesis that the upper cervical spine is weaker than the lower cervical spine in pure flexion and extension bending, which may explain the propensity for upper cervical spine injuries in airbag deployments. An additional objective is to evaluate the relative strength and flexibility of the upper and lower cervical spine in an effort to better understand injury mechanisms, and to provide quantitative data on bending responses and failure modes. Pure moment flexibility and failure testing was conducted on 52 female spinal segments in a pure-moment test frame. The average moment at failure for the O-C2 segments was 23.7+/-3.4Nm for flexion and 43.3+/-9.3Nm for extension. The ligamentous upper cervical spine was significantly stronger in extension than in flexion (p=0.001). The upper cervical spine was significantly stronger than the lower cervical spine in extension. The relatively high strength of the upper cervical spine in tension and in extension is paradoxical given the large number of upper cervical spine injuries in out-of-position airbag deployments. This discrepancy is most likely due to load sharing by the active musculature.


New Method of Injured Nerve Repair.
Innovative surgical techniques form the basis of therapeutic approaches to address the negative consequences of nerve damage. This study evaluated the effectiveness of nerve trunk regeneration after the use of an electrosurgical instrument by looking at the patterns of morphological changes in the injured nerve and the structural elements of the segment motor center. The study was performed on male Wistar rats divided into four groups: group 1, control; group 2, rats with simulated sciatic nerve injury with epineural sutures; 3, rats subjected to an experimental surgical procedure using high-frequency electric welding technology; and 4, rats with simulated sciatic nerve injury without posttransection repair. To study changes in the peripheral stump of the transected nerves and L5 segments of the spinal cord, we used histologic, immunohistochemical, and morphometric methods. At week 12 after the surgery, there were more S-100+ Schwann cells, increased expression of neurofilaments (NFs), and glial fibrillary acidic protein in the peripheral stump in group 3 than in groups 2 and 4, which indicates enhanced neurotization and myelination. Group 3 animals demonstrated reduced expression of S-100 and NFs in the motor center of the spinal cord compared with group 2 that suggests less pronounced reactive changes caused by electric welding technology. The study showed a novel surgical method using an electrosurgical instrument in a welding mode to stimulate regeneration of the injured nerve and to cause less prominent reactive changes in its segment motor center.


Post-COVID-19 syndrome symptoms after mild and moderate SARS-CoV-2 infection.
Post-COVID-19 Syndrome (PCS) is characterized by residual symptoms following the initial recovery from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The prevalence of PCS is known to be the highest among severe and critical forms of the disease. However, the occurrence and risk factors for PCS after mild or moderate SARS-CoV-2 infection has not been extensively investigated. Online and offline via both paper or mailed questionnaires distributed among Jordan collected between 1st and 21st August 2021, including a total number of 800 respondents, of whom 495 had previous mild to moderate COVID-19 infection. The Newcastle post-COVID syndrome Follow-up Screening Questionnaire was modified, translated, and used as a standard instrument for data collection regarding psychological, medical, and socio-economic symptoms post-infection. The primary outcome was the prevalence of PCS after mild to moderate COVID-19 in Jordan. Secondary outcome was the identification of PCS risk factors. The most common PCS symptom was mood disturbance followed by fatigue, anxiety, and myalgia. Female gender significantly increased the risk for multiple PCS symptoms. Age < 30 years was found to be an independent risk factor for myalgia (p = 0.001). PCS is highly prevalent among COVID-19 survivors in Jordan, especially in females and patients with comorbidities. Planning physical and mental rehabilitation services is recommended for those patients with PCS symptoms after mild to moderate COVID-19 infection.


Estrogen induces IDO expression via TGF‑β in chorionic villi and decidua during early stages of pregnancy.
Indoleamine 2,3‑dioxygenase (IDO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternal‑fetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17β‑estradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor β (TGF‑β) and IDO in chorionic villi and decidua tissues. Both TGF‑β and IDO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17β‑estradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IDO expression increased in a dose‑dependent manner in tissue samples cultured in medium containing TGF‑β. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IDO by TGF‑β, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.


Proteome analysis with classical 2D-PAGE.
Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is based on the combination of two orthogonal separation techniques. In the first dimension, proteins are separated by their isoelectric point, a technique known as isoelectric focusing (IEF). There are two important variants of IEF, which are carrier-ampholine (CA)-based IEF and immobilized pH gradient (IPG)-based IEF. In the second dimension, proteins are further separated by their electrophoretic mobility using SDS-PAGE. Finally, proteins can be visualized and quantified by different staining procedures, such as Coomassie, silver, or fluorescence staining. This chapter gives detailed protocols for 2D-PAGE, using both CA- and IPG-based separation in the first dimension.


Production mechanism of quark-gluon plasma in heavy-ion collisions.
A general scheme is proposed here to describe the production of semihard and soft quarks and gluons that form the bulk of the plasma in ultrarelativistic heavy-ion collisions. We show how to obtain the production rates in the extended phase space, including the color part, as a function of time in a consistent manner and without having to make ad hoc assumptions. All the required features-the back reaction on QCD vacuum, the non-Markovian nature of the production, and the quasi particle nature of the partons-are naturally incorporated. We illustrate the results with a realistic albeit toy model and also show how physically tenable source terms may be obtained.


Cephalosporin-aminoglycoside synergism in experimental enterococcal endocarditis.
Despite in vitro demonstrations of synergism against enterococci, combinations of cephalosporin and aminoglycoside antibodies have been ineffective in the therapy of enterococcal endocarditis. Penicillin-gentamicin, cephalothin-gentamicin, and cefazolin-gentamicin were used to treat enterococcal endocarditis in rabbits. A direct relation was observed between the rate of cure and the degree by which the peak serum concentration of penicillin and the cephalosporins exceeded the minimal inhibitory concentration of the enterococcus. Thus, cephalosporin doses which produce serum concentrations which exceed the minimal inhibitory concentration of the enterococcus by several orders of magnitude may, in combination with aminoglycosides, be effective in treating human enterococcal endocarditis.


Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.
Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. A 20-month-old boy presented with failure to thrive, polyuria, polydipsia, and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency, and nephrogenic diabetes insipidus. His initial ophthalmologic examination did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance, and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.


Successful 6-month endurance training does not alter insulin-like growth factor-I in healthy older men and women.
Lean body mass, strength, and endurance decline with advancing age, changes paralleled by declines in anabolic hormones, including growth hormone (GH) and insulin-like growth factor-I (IGF-I). Acute exercise has been shown to stimulate the GH/IGF-I axis, and long-term exercise increases GH. This study examined the effect of endurance training on IGF-I in healthy older men and women. Thirty-one healthy older men (66.9 +/- 1.0 yrs, mean +/- SEM) and 21 healthy older women (67.1 +/- 1.7 yrs) were randomized to either 3d/wk, 6-month endurance (ET3) or stretching/flexibility (SF3) protocols. Another group of 15 healthy older men (69.0 +/- 1.3 yrs) participated in a more intensive 5d/wk, 6-month endurance protocol (ET5). Before and after training, subjects were weight stabilized and participated in maximal exercise tolerance testing, body composition assessment, and fasting blood sampling. ET3 training resulted in a significant increase (14%) in maximal aerobic power (VO2max), significant decreases in body weight (BW), fat mass (FM), and waist/hip ratio (WHR), and a significant increase in fat-free mass (FFM). No significant VO2max or body composition changes were observed in the SF3 group. For the ET5 group, a significant increase (22%) in VO2max and significant decrease in BW, FM, and WHR were observed. No significant changes in IGF-I were observed for any of the three groups. Pre- versus post-training IGF-I values were very stable (r = .86, p < .001) across subjects. Within-subject basal levels of IGF-I in healthy seniors were extremely stable between pre- and post-training assessments. Two endurance training protocols of magnitudes sufficient to significantly increase aerobic capacity and decrease measures of body adiposity did not significantly increase basal levels of IGF-I in healthy older men and women.


Surgical video displays and booms. We answer your questions about selection and installation.
If you're renovating your operating rooms or constructing new ones, you probably have a lot of basic questions about device requirements and the purchasing process. Do devices need to meet electrical safety standards? Is equipment described as "medical grade" better? Is it important to buy your displays from your surgical boom vendor or your integration provider? Here are answers to those and other questions we're often asked.