Chest CT Scan Features to Predict COVID-19 Patients' Outcome and Survival.
Providing efficient care for infectious coronavirus disease 2019 (COVID-19) patients requires an accurate and accessible tool to medically optimize medical resource allocation to high-risk patients. To assess the predictive value of on-admission chest CT characteristics to estimate COVID-19 patients' outcome and survival time. Using a case-control design, we included all laboratory-confirmed COVID-19 patients who were deceased, from June to September 2020, in a tertiary-referral-collegiate hospital and had on-admission chest CT as the case group. The patients who did not die and were equivalent in terms of demographics and other clinical features to cases were considered as the control (survivors) group. The equivalency evaluation was performed by a fellowship-trained radiologist and an expert radiologist. Pulmonary involvement (PI) was scored (0-25) using a semiquantitative scoring tool. The PI density index was calculated by dividing the total PI score by the number of involved lung lobes. All imaging parameters were compared between case and control group members. Survival time was recorded for the case group. All demographic, clinical, and imaging variables were included in the survival analyses. After evaluating 384 cases, a total of 186 patients (93 in each group) were admitted to the studied setting, consisting of 126 (67.7%) male patients with a mean age of 60.4 ± 13.6 years. The PI score and PI density index in the case vs. the control group were on average 8.9 ± 4.5 vs. 10.7 ± 4.4 (p value: 0.001) and 2.0 ± 0.7 vs. 2.6 ± 0.8 (p value: 0.01), respectively. Axial distribution (p value: 0.01), cardiomegaly (p value: 0.005), pleural effusion (p value: 0.001), and pericardial effusion (p value: 0.04) were mostly observed in deceased patients. Our survival analyses demonstrated that PI score ≥ 10 (p value: 0.02) and PI density index ≥ 2.2 (p value: 0.03) were significantly associated with a lower survival rate. On-admission chest CT features, particularly PI score and PI density index, are potential great tools to predict the patient's clinical outcome.


Phase I study of panobinostat in combination with bevacizumab for recurrent high-grade glioma.
Bevacizumab is frequently used to treat patients with recurrent high-grade glioma (HGG), but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects and may work synergistically with VEGF inhibitors. We performed a phase I study to evaluate the safety and tolerability of the combination of orally administered panobinostat with bevacizumab in patients with recurrent HGG. Patients with recurrent HGG were treated on a 3 + 3 trial design. Patients received bevacizumab 10 mg/kg every other week in combination with oral panobinostat. The starting dose of panobinostat was 20 mg three times per week, weekly (cohort 1). Due to concerns for thrombocytopenia with the weekly dosing regimen, the protocol was amended to examine an every other week regimen. Cohort 2 received panobinostat 20 mg three times per week, every other week, and cohort 3 received 30 mg three times per week, every other week. Dose-limiting toxicity during the first 30 days was used to determine the maximum-tolerated dose. Twelve patients (median age 50, median KPS 90) with recurrent HGG were enrolled. One dose-limiting toxicity (DLT) (Grade 3 thrombocytopenia) was observed in cohort 1. No DLTs were observed in cohorts 2 and 3. The following grade 3 toxicities were seen in one patient each: thrombocytopenia, hypophosphatemia, esophageal hemorrhage, and deep venous thrombosis. There were no grade 4 or 5 toxicities. There were three patients with partial responses and seven with stable disease. The recommended doses for further study are oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. A phase II clinical trial in recurrent HGG is underway.


Fibrin nanoparticles as Possible vehicles for drug delivery.
Several issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem. Fibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice. FNP were spherical with size ranging from 25 to 28nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-α and downregulation of IL-6 cytokines after 6h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic. Owing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications. Our results demonstrate the safe and promising use of FNP for biomedical applications.


Food safety: current situation, unaddressed issues and the emerging priorities.
This paper reviews the topic of food safety with reference to the Eastern Mediterranean Region. The differing views of food safety and the current situation with regard to ensuring food safety are presented. Also discussed are some of the unaddressed issues and challenges related to food safety. The new conditions that have arisen in the modern world which have facilitated the emergence of pathogens are presented, such as changes in animal husbandry, changes in international trade and travel, lifestyle and consumer changes. The urgent need for action in order to reduce the risk of microbiological and chemical foodborne diseases is emphasized. The food chain starts from farm and ends at fork; controlling this complex process requires an integrated approach and a responsible authority to oversee it in order to protect and promote food safety.


Secure OFDM with Peak-to-Average Power Ratio Reduction Using the Spectral Phase of Chaotic Signals.
In this paper, a new physical layer security technique is proposed for Orthogonal Frequency Division Multiplexing (OFDM) communication systems. The security is achieved by modifying the OFDM symbols using the phase information of chaos in the frequency spectrum. In addition, this scheme reduces the Peak to Average Power Ratio (PAPR), which is one of the major drawbacks of OFDM. The Selected Mapping (SLM) technique for PAPR reduction is employed to exploit the random characteristics of chaotic sequences. The reduction with this algorithm is shown to be similar to that of other SLM schemes, but it has lower computational complexity and side information does not have to be sent to the receiver. The security of this technique stems from the noise like behavior of chaotic sequences and their dependence on the initial conditions of the chaotic generator (which are used as the key). Even a slight difference in the initial conditions will result in a different phase sequence, which prevents an eavesdropper from recovering the transmitted OFDM symbols.


[The dry eye].
After reviewing the anatomy and pathophysiology of the lacrimal circuit, the authors describe the diagnostic approach to dry eye syndrome. Two very different entities can be distinguished: acute dryness generally due to a defect of the palpebral lining, for which urgent treatment is required to prevent corneal perforation, and chronic dryness, generally due to a reduction of lacrimal secretion. The aetiological survey must look for a reversible cause, dominated by drugs. Treatment is symptomatic in every case, consisting of the regular prescription of artificial tears. The use of lacrimal plugs to obstruct the lacrimal draining ducts constitute second-line treatment and may improve the functional tolerance.


[The effectiveness of population-based breast cancer screening programme].
Well-organised mammography screening programme can significantly reduce the breast cancer mortality However, changes in mortality rates take a long time thus some early indicators are usually used to monitor the effectiveness of the programme. If these operational objectives are accomplished then the programme can replicate the mortality reduction achieved in randomised trials. To evaluate the quality of breast cancer screening programme in the region of Lower Silesia during the first year of its operating. Centrally organised breast cancer screening has been introduced since the beginning of the year 2007. This population-based programme is designed for women aged 50-69. Females undergoing treatment or being followed-up due to breast cancer are not invited. Screen-film two-view mammography without clinical examination is used as a screening test which is to be performed every two years. The second level diagnostic tools are breast clinical examination and additional imaging (mammography and ultrasound). Following further assessment women are referred to the examination at the routine round length of the programme, at the less interval (short-term recall) or biopsy procedures. Quality assessment was done via early indicators according to the European guidelines. The attendance rate was 41% (79,143 women screened within 192,613 eligible population for one year). Technical repeat rate, further assessment rate, and short-term recall rate were: 0.26%, 6.85%, and 0.91%, respectively. Pathologically confirmed breast cancer was revealed in 364 women giving the detection rate 4.59 for 1000. Cancer detection rate to expected incidence ratio was 3.35. Mammography service performed during the first year of breast cancer screening programme in the region of Lower Silesia conforms to quality assessment parameters recommended by the European guidelines at the acceptable level. The main problem at the start of this programme is too low coverage. Invitation process must be strongly intensified to improve long-term effectiveness and to significantly reduce breast cancer mortality.


Autologous/Allogeneic Hematopoietic Cell Transplantation versus Tandem Autologous Transplantation for Multiple Myeloma: Comparison of Long-Term Postrelapse Survival.
We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in 46% of the auto/allo patients, compared with 26% of the auto/auto patients. The 6-year postrelapse survival was better in the auto/allo group compared with the auto/auto group (44% versus 35%; P = .05). Mortality due to MM was 69% (n = 101) in the auto/allo group and 83% (n = 229) deaths in auto/auto group. In multivariate analysis, both cohorts had a similar risk of death in the first year after relapse (hazard ratio [HR], .72; P = .12); however, for time points beyond 12 months after relapse, overall survival was superior in the auto/allo cohort (HR for death in auto/auto =1.55; P = .005). Other factors associated with superior survival were enrollment in a clinical trial for HCT, male sex, and use of novel agents at induction before HCT. Our findings shown superior survival afterrelapse in auto/allo HCT recipients compared with auto/auto HCT recipients. This likely reflects a better response to salvage therapy, such as immunomodulatory drugs, potentiated by a donor-derived immunologic milieu. Further augmentation of the post-allo-HCT immune system with new immunotherapies, such as monoclonal antibodies, checkpoint inhibitors, and others, merit investigation.


Successful catheter ablation of epicardial ventricular tachycardia worsened by cardiac resynchronization therapy.
Soon after an upgrade from a single-chamber implantable cardioverter-defibrillator (ICD) to cardiac resynchronization therapy (CRT) with an ICD, a 64-year-old man with non-ischaemic cardiomyopathy began to have increasingly frequent ICD shocks for slow ventricular tachycardia (VT). At electrophysiological study, no clinical VT was induced by endocardial right ventricular pacing, but was easily induced by epicardial left ventricular (LV) pacing via a subxiphoid pericardial approach. The VT was successfully ablated on the LV epicardial surface. This case suggests that epicardial catheter ablation may be an alternative for managing CRT-induced proarrhythmias without the inactivation of LV pacing.


European Practice Database: comparative results of the year 1 pilot project.
The European Practice Database (EPD) project, developed by the Research Board (RB) of EDTNA/ERCA, intended to collect data on renal practice at centre level in different European countries. During the pilot phase of the project (2002-2003), Czech Republic, Italy (North East) and England (North) participated with two thirds of all their eligible dialysis centres. Comparative results presented in this paper focus on centre size and patient characteristics, peritoneal and haemodialysis techniques, transplantation, infection control and the employment of technicians, dietitians and social workers in dialysis centres. At centre level, EPD results will enable in-depth evaluation of personal practice. International comparison of the results will stimulate further research and the development of new guidelines.


Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice.
Indole-3-carbinol (I3C) is a potent inducer of cytochrome P450 enzymes in many species, including humans. We therefore studied alterations in the cytochrome P450-dependent metabolism of estradiol in different strains of mice consuming I3C in semisynthetic powdered diets at doses ranging from 250 to 5000 p.p.m. (34-700 mg/kg/day) for different periods of time. In short-term metabolic studies (3 weeks), wet liver weight increased in SW and C3H/OuJ mice in a dose-responsive manner. Dietary I3C increased the cytochrome P450 content measured in hepatic microsomes, as well as the extent of estradiol 2-hydroxylation, up to 5-fold. In a long-term feeding experiment (8 months), female C3H/OuJ mice consumed synthetic diets containing I3C at 0, 500 or 2000 p.p.m. Mammary tumor incidence and multiplicity were significantly lower at both doses of I3C, and tumor latency was prolonged in the high-dose group. We conclude that I3C is an inducer of hepatic P450-dependent estrogen metabolism in mice, and that it is chemopreventive in the C3H/OuJ mouse mammary tumor model. This protective effect may be mediated in part by the increased 2-hydroxylation and consequent inactivation of endogenous estrogens.


Posttraumatic stress disorder, trauma exposure, and the current health of Canadian bus drivers.
Previous studies of veterans have linked posttraumatic stress disorder (PTSD) after combat-related trauma to increased reports of health problems. It is unclear whether this association between PTSD and increased health problems generalizes to civilians who are exposed to a broader array of traumatic events. We also do not know whether trauma exposure is associated with increased health problems in individuals who do not develop PTSD. Using a non-treatment-seeking civilian sample, we examined whether lifetime PTSD or trauma exposure by itself was associated with current health problems. Using a cross-sectional design and self-report measures, we evaluated urban Canadian bus drivers (n = 342) on trauma exposure, lifetime PTSD, and current health problems. Based on their responses, we divided our sample into individuals who had never experienced trauma (n = 91), trauma-exposed individuals who had never developed PTSD (n = 218), and persons who developed PTSD at some point after trauma (n = 33). We compared these groups on health problems, treatment service use, and health assessment measures. The PTSD group reported increased health complaints, more frequent use of health treatments, and poorer health self-ratings compared with the exposed non-PTSD and nonexposed groups. Trauma-exposed drivers without PTSD did not differ from unexposed drivers on any health measure. Controlling for sex and trauma frequency did not alter our findings. Trauma exposure that leads to PTSD is associated with increased health problems, while trauma exposure alone is not. Our results extend previous findings to a broader civilian context and clarify associations between trauma exposure and health.


Subwavelength polarization splitter-rotator with ultra-compact footprint.
An ultra-compact polarization splitter-rotator with a discretized subwavelength nanostructure is demonstrated on the silicon-on-insulator platform. The device has a length of only 7.92 μm. For TE0-TE0, a low insertion loss (<0.2 dB), low crosstalk (<-20 dB), and high extinction ratio (>40 dB) are achieved over a broad wavelength range from 1500 nm to 1600 nm. For TM0-TE0, the insertion loss is lower than 1 dB over 40 nm bandwidth (1530-1570 nm). The crosstalk is lower than -25 dB, and the extinction ratio is larger than 20 dB, from 1500 nm to 1600 nm.


[Acute monocytic leukemia after orthotopic liver transplantation: clinical features, molecular genetics, and significance thereof].
To study the clinical features and molecular genetics of acute monocytic leukemia (AML) after orthotopic liver transplantation and significance thereof. The clinical manifestations, laboratory findings, development, diagnosis, treatment, and prognosis of the first case of AML after orthotopic liver transplantation in the world, a Chinese, male, aged 46, were observed. RT-PCR was used to analyze the mRNA expression of FLT3, Pim-1, and Hsp-70 in the bone marrow mononuclear cells (BMMCs) of the patient. Nucleotide sequence analysis was used to detect the mutation of FLT3-ITD. Flow cytometry was used to examine the protein expression of C-kit, a stem cell factor receptor, and platelet derived growth factor receptor-alpha (PDGFRalpha). (1) Three months after the orthotopic liver transplantation the patient manifested symptoms and signs of anemia and thrombocytopenia. Laboratory tests found increase of white blood cells and myeloblasts with Auer's rods. Cytogenetic analysis showed a genotype of 46XY/47XY with an extra chromosome 8. Bone marrow examination revealed increased promonocytes. The diagnosis of chronic myelomonocytic leukemia was made. Five months after the liver transplantation the disease developed to AML. The patient underwent combined chemotherapy (HA or DA regimens) for 5 courses and showed a partial remission both hematologically and in bone marrow examination at first, however, became resistant to all chemotherapeutic agents. RT-PCR showed absence of wild type FLT3 allele. At last the patient died of infection. (2) A FLT3-ITD mutation of "insertion" type was identified in the BMMCs. The Pim-1 mRNA was weakly expressed and the expression of Hsp-70 mRNA was upregulated in the BMMCs. (3) The protein expression of C-kit and that of PDGFRalpha were both upregulated in the BMMCs as showed by flow cytometry. Orthotopic liver transplantation may be complicated with acute leukemia heterogeneous in clinical features and hematology. Certain defects in cytogenetics/molecular genetics may attribute to unfavorable prognosis.


Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity.
We sought to determine the effects of longitudinal loading (artificial gravity) on skeletal muscle protein kinetics in 15 healthy young males after 21 days of 6 degrees head-down tilt bed rest [experimental treatment (Exp) group: n = 8, 31 +/- 1 yr; control (Con) group; n = 7, 28 +/- 1 yr, means +/- SE]. On days 1 and 21 of bed rest, postabsorptive venous blood samples and muscle biopsies (vastus lateralis and soleus) were obtained during a 1-h pulse bolus infusion protocol (0 min, l-[ring-(13)C(6)]phenylalanine, 35 mumol/kg; 30 min, l-[ring-(15)N]phenylalanine, 35 mumol/kg). Outcome measures included mixed muscle fractional synthesis (FSR) and breakdown rates (FBR). The Exp group experienced 1 h of longitudinal loading (2.5G at the feet) via a short-radius centrifuge during each day of bed rest. Mixed muscle FSR in the Con group was reduced by 48.5% (day 1, 0.081 +/- 0.000%/h vs. day 21, 0.042 +/- 0.000%/h; P = 0.001) in vastus lateralis after 21 days of bed rest, whereas the Exp group maintained their rate of protein synthesis. A similar but nonsignificant change in FSR was noted for the soleus muscle (Exp, -7%; Con, -22%). No changes in muscle protein breakdown were observed. In conclusion, 1 h of daily exposure to artificial gravity maintained the rate of protein synthesis of the vastus lateralis and may represent an effective adjunct countermeasure to combat the loss of muscle mass and functional during extended spaceflight.


DNA-Mediated Size-Selective Nanoparticle Assembly for Multiplexed Surface Encoding.
Multiplexed surface encoding is achieved by positioning two different sizes of gold nanocubes on gold surfaces with precisely defined locations for each particle via template-confined, DNA-mediated nanoparticle assembly. As a proof-of-concept demonstration, cubes with 86 and 63 nm edge lengths are assembled into arrangements that physically and spectrally encrypt two sets of patterns in the same location. These patterns can be decrypted by mapping the absorption intensity of the substrate at λ = 773 and 687 nm, respectively. This multiplexed encoding platform dramatically increases the sophistication and density of codes that can be written using colloidal nanoparticles, which may enable high-security, high-resolution encoding applications.


Exploring the genomes: from Arabidopsis to crops.
Model systems have played a crucial role for understanding biological processes at genetic, molecular and systems levels. Arabidopsis thaliana is one of the best studied model species for higher plants. Large genomic resources and mutant collections made Arabidopsis an excellent source for functional and comparative genomics. Rice and Brachypodium have a great potential to become model systems for grasses. Given the agronomic importance of grass crops, it is an attractive strategy to apply knowledge from Arabidopsis to grasses. Despite many efforts successful reports are sparse. Knowledge transfer should generally work best between orthologous genes that share functionality and a common ancestor. In higher plants, however, recent genome projects revealed an active and rapid evolution of genome structure, which challenges the concept of one-to-one orthologous mates between two species. In this study, we estimated on the example of protein families that are involved in redox related processes, the impact of gene expansions on the success rate for a knowledge transfer from Arabidopsis to the grass species rice, sorghum and Brachypodium. The sparse synteny between dicot and monocot plants due to frequent rearrangements, translocations and gene losses strongly impairs and reduces the number of orthologs detectable by positional conservation. To address the limitations of sparse synteny and expanded gene families, we applied for the detection of orthologs in this study orthoMCL, a sequence-based approach that allows to group closely related paralogs into one orthologous gene cluster. For a total of 49 out of 170 Arabidopsis genes we could identify conserved copy numbers between the dicot model and the grass annotations whereas approximately one third (34.7%, 59 genes) of the selected Arabidopsis genes lack an assignment to any of the grass genome annotations. The remaining 62 Arabidopsis genes represent groups that are considerably biased in their copy numbers between Arabidopsis and all or most of the three grass genomes.


Spatial distribution and speciation of arsenic in peat studied with Microfocused X-ray fluorescence spectrometry and X-ray absorption spectroscopy.
Arsenic binding by sulfhydryl groups of natural organic matter (NOM) was recently identified as an important As sequestration pathway in the naturally As-enriched minerotrophic peatland Gola di Lago, Switzerland. Here, we explore the microscale distribution, elemental correlations, and chemical speciation of As in the Gola di Lago peat. Thin sections of undisturbed peat samples from 0-37 cm and 200-249 cm depth were analyzed by synchrotron microfocused X-ray fluorescence (μ-XRF) spectrometry and X-ray absorption spectroscopy (μ-XAS). Additionally, peat samples were studied by bulk As, Fe, and S K-edge XAS. Micro-XRF analyses showed that As in the near-surface peat was mainly concentrated in 10-50 μm sized hotspots, identified by μ-XAS as realgar (α-As4S4). In the deep peat layer samples, however, As was more diffusely distributed and mostly associated with particulate NOM of varying decomposition stages. The NOM-associated As was present as trivalent As bound by sulfhydryl groups. Arsenopyrite (FeAsS) and arsenian pyrite (FeAsxS2-x) of <25 μm size, which have escaped detection by bulk As and Fe K-edge XAS, were found as minor As species in the peat. Bulk S K-edge XAS revealed that the deep peat layers were significantly enriched in reduced organic S species. Our findings suggest an authigenic formation of realgar and arsenopyrite in strongly reducing microenvironments of the peat and indicate that As(III)-NOM complexes are formed by the passive sorption of As(III) to NOM. This reaction appears to be favored by a combination of abundant reduced organic S and comparatively low As solution concentrations preventing the formation of secondary As-bearing sulfides.


Structural Characterization of Rh and RhAu Dendrimer-Encapsulated Nanoparticles.
We report the structural characterization of 1-2 nm Rh and RhAu alloy dendrimer-encapsulated nanoparticles (DENs) prepared by chemical reduction with NaBH4. In contrast to previously reported results, in situ and ex situ X-ray absorption spectroscopic experiments indicate that only a fraction of the Rh3+ present in the precursors are reduced by NaBH4. Additional structural analysis of RhAu alloy DENs using extended X-ray absorption fine structure spectroscopy leads to a model in which there is significant segregation of Rh and Au within the nanoparticles. In Rh-rich alloy DENs, Au atoms are segregated on the nanoparticle surface.


Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis.
The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.


Formation of polychlorinated dibenzo-p-dioxins/dibenzofurans from soot of benzene and o-dichlorobenzene combustion.
Soots were prepared from flame combustion of benzene and o-dichlorobenzene (ODCB), creating one soot without carbon-chlorine bonds (benzene soot) and one with such bonds (ODCB soot). ODCB soot was tested for PCDD/F formation between 277 and 600 degrees C without additional chlorine, but levels were very low. Copper and Cu2O were added as potential catalysts for ODCB soot oxidation, but levels of PCDD/F observed were even lower than without these additives. Both benzene soot and ODCB soot produced PCDD/F after adding CuCl2 to the reaction mixtures, suggesting that a (volatile) metal chloride was needed in order for PCDD/F formation to take place. Under the various conditions of [Cu2+], time, and temperature tested, ODCB soot was always more reactive than benzene soot in forming PCDD/F. It seemed plausible that, despite the fact that CuCl2 was very effective in creating C-Cl bonds in benzene soot, the C-Cl bonds created in ODCB soot during preparation were of a reactivity so as to make this soot especially prone to PCDD/F formation. High temperature (gas phase) chlorination of soots by HCI or other chlorinating agents, followed by deposition of these soots and condensed metal chlorides on the ducts and walls of the postcombustion zone, could create an effective mechanism for de novo formation of PCDD/F.


The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response.
High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.


A 3D Stable Metal⁻Organic Framework for Highly Efficient Adsorption and Removal of Drug Contaminants from Water.
We herein selected a 3D metal⁻organic framework decorated with carboxylate groups as an adsorbent to remove the pharmaceutical molecules of diclofenac sodium and chlorpromazine hydrochloride from water. The experiment aimed at exploring the effect factors of initial concentration, equilibrium time, temperature, pH and adsorbent dosage on the adsorption process. The adsorption uptake rate of the diclofenac sodium is much higher than that of the chlorpromazine hydrochloride. This paper presents the high adsorption capacity of diclofenac sodium, in which porous MOFs are used for the removal of drug contaminants from water. According to linear fitting with adsorption isotherm equation and kinetic equations, diclofenac sodium conforms to the Langmuir model and pseudo-first-order kinetic equation, while chlorpromazine hydrochloride accords with the Temkin model and pseudo-second-order kinetic equation. The results of the study indicate that the title compound could be a promising hybrid material for removing diclofenac sodium and chlorpromazine hydrochloride from wastewater.


[Risk factors for nosocomial bloodstream infections in a neonatal intensive care unit].
To assess the risk factors for nosocomial blood-stream infection (BSI) in a neonatal intensive care unit (NICU). Clinical data from the neonates admitted to the NICU in the St. Louis Children's Hospital in Washington University School of Medicine between January 2005 and December 2006 were retrospectively studied. A total of 1 290 neonates were included. Overall, 175 nosocomial BSIs occurred. Catheter-related BSIs accounted for 62.3% (109 cases). The incidence of nosocomial BSI was 4.22 per 1 000 patient-days. Logistic regression analysis revealed that low gestational age, low Apgar scores at 5 minutes, use of central venous catheter (CVC), and longer CVC use were risk factors for the development of nosocomial BSI. In the subgroup of neonates with CVC, mechanical ventilation was an additional independent risk factor for BSI. Catheter-related BSI is the major source of nosocomial BSI in the NICU. Prematurity, low Apgar scores at birth and prolonged CVC use are risk factors for the development of BSI.


CB11Me11 boronium ylides: carba-closo-dodecaboranes with a naked boron vertex.
In pentane solution, 2 equiv of the icosahedral CB(11)Me(12)(*) radical cleaves the Si-Si bond of hexaalkyldisilanes by boron to silicon methyl transfer with formation of 2 equiv of methyltrialkylsilanes. The loss of a methyl radical converts the CB(11)Me(12)(*) radical into an internally charge-compensated "boronium ylide" CB(11)Me(11) with a naked vertex, which can be formally viewed as a deprotonated hypercloso carborane. It has been isolated as an air-sensitive solid, stable only below approximately -60 degrees C. The naked vertex appears to be in position 12 since the material reacts instantaneously with alcohols and ethers to form the 12-alkoxy anions 12-CB(11)Me(11)OR. It reacts with many other nucleophiles to yield more complex mixtures containing similar products. DFT calculations for the four CB(11)Me(11) isomers give closed-shell ground-state electronic structures. For the isomer with naked vertex 12, a DFT computational search failed to reveal any skeletal dimers, apparently due to excessive methyl-methyl repulsions, and only a cyclic dimer bound through weak interactions of one of the 7-methyl hydrogen atoms on each cage with the empty exocyclic orbitals on B12 of the other cage was found. Natural hybrid orbital populations suggest that the three possible isomers of monomeric boronium ylides are close to true singlet ylides, with triplet states approximately 50 kcal/mol higher. The calculated electronic structure of the carbonium ylide is close to a singlet carbene, with a triplet state approximately 16 kcal/mol higher. An attempted preparation of Me(3)C(+)CB(11)Me(12)(-) yielded neopentane and products consistent with a sequential loss of methyl groups from the carborane cage with a transient formation of similar boronium ylides. Probable mechanisms of these methyl transfer reactions are considered, and the possibly quite general role of "ylide" structures in Lewis acid induced substitution reactions on the boron vertices of carboranes and boranes is noted.


Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis.
To determine whether renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis (LAM) express estrogen receptor (ER) and progesterone receptor (PR). Retrospective study of archival tissue. Twelve women with LAM and angiomyolipomas. Fox Chase Cancer Center. ER and PR expression was studied using immunohistochemistry. The hormonal status of the patients at the time of resection of the angiomyolipoma was determined. Ten of the angiomyolipomas had ER immunoreactivity (83%), and all 12 had PR immunoreactivity (100%). The ER and PR positivity was in the smooth muscle component of the angiomyolipomas only. For five women, pulmonary LAM specimens were also available; two were ER positive (40%), and all five were PR positive (100%). All four angiomyolipomas from women receiving progesterone therapy were ER and PR positive. One tumor from a woman receiving tamoxifen was ER negative and strongly PR positive. One woman was pregnant; her tumor was ER and PR positive. ER and PR expression is frequent in renal angiomyolipoma cells from women with LAM. PR was more consistently present than ER in angiomyolipomas and in LAM. Our data suggest that angiomyolipoma growth could be affected by hormonal factors. If the growth of LAM-associated angiomyolipomas slows during hormonal therapy, there are two potential implications for LAM patients: first, angiomyolipoma size could serve as a measurable indication of response to hormonal therapy; and second, surgical removal of angiomyolipomas might be avoided in some cases.


Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations.
Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent case-control study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] = 0.69, 95% confidence interval [95% CI] = 0.55-0.87) and replication stage (OR = 0.80, 95% CI = 0.68-0.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream of TERT) was significantly associated with a decreased risk of gastric cancer (OR = 0.76, 95% CI = 0.67-0.87, P = 5.35 × 10(-5)). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P = 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.


Self-recognition affects plant communication and defense.
Animals have the ability to distinguish self from non-self, which has allowed them to evolve immune systems and, in some instances, to act preferentially towards individuals that are genetically identical or related. Self-recognition is less well known for plants, although recent work indicates that physically connected roots recognize self and reduce competitive interactions. Sagebrush uses volatile cues emitted by clipped branches of self or different neighbours to increase resistance to herbivory. Here, we show that plants that received volatile cues from genetically identical cuttings accumulated less natural damage than plants that received cues from non-self cuttings. Volatile communication is required to coordinate systemic processes such as induced resistance and plants respond more effectively to self than non-self cues. This self/non-self discrimination did not require physical contact and is a necessary first step towards possible kin recognition and kin selection.


Intraoperative Mass Spectrometry Platform for IDH Mutation Status Prediction, Glioma Diagnosis, and Estimation of Tumor Cell Infiltration.
Surgical tumor resection is the primary treatment option for diffuse glioma, the most common malignant brain cancer. The intraoperative diagnosis of gliomas from tumor core samples can be improved by use of molecular diagnostics. Further, residual tumor at surgical margins is a primary cause of tumor recurrence and malignant progression. This study evaluates a desorption electrospray ionization mass spectrometry (DESI-MS) system for intraoperative isocitrate dehydrogenase (IDH) mutation assessment, estimation of tumor cell infiltration as tumor cell percentage (TCP), and disease status. This information could be used to enhance the extent of safe resection and so potentially improve patient outcomes. A mobile DESI-MS instrument was modified and used in neurosurgical operating rooms (ORs) on a cohort of 49 human subjects undergoing craniotomy with tumor resection for suspected diffuse glioma. Small tissue biopsies (ntotal = 203) from the tumor core and surgical margins were analyzed by DESI-MS in the OR and classified using univariate and multivariate statistical methods. Assessment of IDH mutation status using DESI-MS/MS to measure 2-hydroxyglutarate (2-HG) ion intensities from tumor cores yielded a sensitivity, specificity, and overall diagnostic accuracy of 89, 100, and 94%, respectively (ncore = 71). Assessment of TCP (categorized as low or high) in tumor margin and core biopsies using N-acetyl-aspartic acid (NAA) intensity provided a sensitivity, specificity, and accuracy of 91, 76, and 83%, respectively (ntotal = 203). TCP assessment using lipid profile deconvolution provided sensitivity, specificity, and accuracy of 76, 85, and 81%, respectively (ntotal = 203). Combining the experimental data and using PCA-LDA predictions of disease status, the sensitivity, specificity, and accuracy in predicting disease status are 63%, 83%, and 74%, respectively (ntotal = 203). The DESI-MS system allowed for identification of IDH mutation status, glioma diagnosis, and estimation of tumor cell infiltration intraoperatively in a large human glioma cohort. This methodology should be further refined for clinical diagnostic applications.


Acid and base hydrolysis of lipid A from Enterobacter agglomerans as monitored by electrospray ionization mass spectrometry: pertinence to detoxification mechanisms.
Lipopolysaccharides (LPS), which are endotoxins found in the cell wall of Gram-negative bacteria, are common components of organic dusts that cause or contribute to symptoms associated with organic dust diseases. The lipid A subgroup within LPS is believed to be responsible for the toxicity. Acid and base treatments, which can be effective detoxification methods, were performed on lipid A from Enterobacter agglomerans (EA), a bacterium commonly found in field cotton. Negative-ion electrospray ionization mass spectrometry was employed to characterize the post-treatment structural changes to lipid A. Acid treatment (1% acetic acid, 100 degrees C) hydrolyzed the ester side-chains of lipid A. It was found that the ester-linked palmitoyl group was the most labile to acid hydrolysis. Hydrolysis of the palmitoyl moiety conformed to pseudo-first-order chemical reaction kinetics with a rate constant for decomposition of heptacyl-lipid A from Enterobacter agglomerans of approximately 3.3 x 10(-3) min-1. An order of lability of lipid A acyl side-chains to acid hydrolysis was also deduced: R4' (palmitoyl) > R1' (myristoyl or hydroxymyristoyl) > R3 (hydroxymyristoyl at position 3) > R1 (oxymyristoyl group at position 3') > R2' (lauroyl). Base treatment (0.05 M NaOH in 95% EtOH, 65 degrees C) was shown to be more effective at cleaving ester-linked side-chains. In addition, mass spectral evidence suggests that opening of the pyranose rings of the disaccharide backbone of lipid A and/or removal of the phosphoryl groups may be occurring during base treatment. This study sheds light on mechanistic aspects of treatment procedures leading to the detoxification of endotoxins.


Pharmacological studies of lappaconitine: supraspinal-spinal interaction in antinociception.
Changes in lappaconitine levels in blood, brain and spinal cord following subcutaneous (s.c.) injection were correlated with the analgesic activity at intervals up to 90 minutes after injection. In the mouse, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections of amounts corresponding to ED50 values in the tail pinch method (i.c.v.: 2333 ng/mouse; i.t.: 1127 ng/mouse) gave peak lappaconitine levels of 1300 ng/g brain and 761 ng/g spinal cord, respectively. However, injection of lappaconitine at ED50 by the s.c. route (7 mg/kg) gave lower peak lappaconitine levels of 320 ng/g brain and 214 ng/g spinal cord. The responses to i.c.v., i.t. and combined i.c.v. plus i.t. administration of lappaconitine were evaluated by the determination of ED50 values, which were plotted as an isobologram. The experimental point is not significantly different from the theoretical additive ED50 point. When a dose equal to the experimental additive ED50 value (i.c.v., i.t. = 620, 413 ng/mouse) was injected, peak lappaconitine levels reached 344 ng/g brain and 241 ng/g spinal cord. Thus, the equianalgesic doses of lappaconitine (ED50 by the s.c. route and additive ED50 by the i.c.v. plus i.t. route) gave closely similar concentrations of the drug in brain and spinal cord. These results indicate that a simultaneous action of lappaconitine on supraspinal and spinal sites is likely to be important for the analgesia produced by systemically administered lappaconitine.


Transfer of pre-embryos donated and fertilized in vivo to recipients given a steroid replacement therapy.
This study describes eleven procedures of non-surgical recovery of preimplantation conceptuses from the uteri of eight fertile donor women and the transfer of the recovered pre-embryos into the uteri of infertile recipients with primary ovarian failure, or with hypothalamic--pituitary failure. Conjugated oestrogens and progesterone were administered to recipients as replacement steroids during the first 20 weeks of pregnancy, in order to produce a secretory endometrium allowing nidation and development of the transferred conceptuses. Five pre-embryo transfers resulted in two viable pregnancies and one early abortion. Non-surgical pre-embryo transfer is a simple and practical method for providing donated ova to women lacking efficient ovarian function.


Silkworms transformed with chimeric silkworm/spider silk genes spin composite silk fibers with improved mechanical properties.
The development of a spider silk-manufacturing process is of great interest. However, there are serious problems with natural manufacturing through spider farming, and standard recombinant protein production platforms have provided limited progress due to their inability to assemble spider silk proteins into fibers. Thus, we used piggyBac vectors to create transgenic silkworms encoding chimeric silkworm/spider silk proteins. The silk fibers produced by these animals were composite materials that included chimeric silkworm/spider silk proteins integrated in an extremely stable manner. Furthermore, these composite fibers were, on average, tougher than the parental silkworm silk fibers and as tough as native dragline spider silk fibers. These results demonstrate that silkworms can be engineered to manufacture composite silk fibers containing stably integrated spider silk protein sequences, which significantly improve the overall mechanical properties of the parental silkworm silk fibers.


Alpha-fetoprotein.
The past year has seen major challenges to existing maternal serum alpha-fetoprotein testing protocols for both neural tube defects and chromosomal anomalies. These challenges are reviewed along with the physiology of alpha-fetoprotein; the use of amniocentesis, ultrasonography, and additional serum markers in women with elevated alpha-fetoprotein levels; and epidemiologic implications of maternal serum alpha-fetoprotein screening.


The impact of rural residence on multiple hospitalizations in nursing facility residents.
This study explored issues surrounding hospitalization rates among rural and urban nursing facility (NF) residents. Data from the Minimum Data Set (MDS+) collected by states participating in the national Multi-State Case Mix Demonstration were used to assess whether rural NF residents experience higher rates of hospitalization compared with urban residents and to understand the extent that resident, facility, and market/area characteristics contribute to these differences. Rural NF residents were more likely than urban residents to have multiple hospitalizations. Further analysis demonstrated that the effect of rural residence on the probability of multiple hospitalizations is greater among newly admitted rural residents than among rural residents not classified as new admissions. In addition to rural residence, other factors associated with an increased likelihood of multiple hospitalizations included state of residence, diagnosis of congestive heart failure, and no discharge planned at the time of NF admission. The findings of this study have important implications for both clinical care and health policy related to the financing and administration of NFs.


TARGETING TARGETED TREATMENT FOR IMMUNE AND NON-IMMUNE KIDNEY DISEASES.
We have found that calcium calmodulin kinase IV is increased in T cells, podocytes, and mesangial cells from patients with systemic lupus erythematosus, as well as in lupus-prone mice, podocytes of patients with focal segmental glomerulosclerosis, and in mice injected with doxorubicin. We showed that this accounts for aberrant T cell function and glomerular damage. Using nanoparticles (nlg) loaded with a small drug inhibitor of calcium calmodulin kinase IV and tagged with antibodies directed to CD4 we have been able to show inhibition of autoimmunity and lupus nephritis. Also, using nlg tagged with antibodies to nephrin, we showed suppression of nephritis in lupus-prone mice and of glomerular damage in mice exposed to doxorubicin. We propose the development of approaches to deliver drugs to cells in a targeted and precise manner.


[Oxynorm® instant versus Tradonal® odis as level 2 analgesic in an emergency service : a monocentric double blind randomized non-inferiority study].
Pain is one of the most common reasons for consultation in the ER. As far as class II analgesics are concerned, tramadol is most usually used. According to some data from the literature, it would seem that oxycodone and tramadol are equivalent in terms of analgesia. We have tried to prove that oxycodone (Oxynorm® instant) is not less effective than tramadol (Tradonal® odis) in an emergency unit. This is a prospective, monocentric, randomized study carried out amongst ambulatory patients. Those included in the study were given 1 g of paracetamol and a weight-ajusted dose of either tramadol or oxycodone. Every 30 minutes, a simple numerical scale (NS) was established and the clinical parameters were checked. We studied a total of 121 patients divided into 2 groups. There is an average difference of -1.47 between the average ?NS of the oxycodone group and the average ?NS of the tramadol group, with a confidence interval of 95 % (-9.42 - 6.48). The confidence interval does not cross the -10 line considered as the acceptable loss of efficiency, which allows us to conclude that oxycodone is not inferior to tramadol. As far as the adverse effects studied are concerned, there is no significant link between the treatment and the appearance of any side effect.


Narrow-bandwidth sensing of high-frequency fields with continuous dynamical decoupling.
State-of-the-art methods for sensing weak AC fields are only efficient in the low frequency domain (<10 MHz). The inefficiency of sensing high-frequency signals is due to the lack of ability to use dynamical decoupling. In this paper we show that dynamical decoupling can be incorporated into high-frequency sensing schemes and by this we demonstrate that the high sensitivity achieved for low frequency can be extended to the whole spectrum. While our scheme is general and suitable to a variety of atomic and solid-state systems, we experimentally demonstrate it with the nitrogen-vacancy center in diamond. For a diamond with natural abundance of 13C, we achieve coherence times up to 1.43 ms resulting in a smallest detectable magnetic field strength of 4 nT at 1.6 GHz. Attributed to the inherent nature of our scheme, we observe an additional increase in coherence time due to the signal itself.


Infective endocarditis in patients with liver cirrhosis: a systematic review.
Liver cirrhosis is an increasing cause of mortality and morbidity in developed countries. Infective Endocarditis (IE) is an uncommon disease with notable morbidity and mortality. Even though cirrhosis is associated with immune dysfunction and increased occurrence of bacterial infection, IE is infrequently diagnosed in these patients. Thus, the purpose of this study was to systematically review all published cases of IE in patients with cirrhosis in the literature. A systematic review of PubMed, Scopus and Cochrane (through 23th April 2020) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of IE in patients with cirrhosis was performed. A total of 78 studies, containing data of 602 patients, were included. A prosthetic valve was present in 17.8%, while the most common causative pathogen was S. aureus in 26% followed by Streptococcus spp in 16.8%. Aortic valve was the most commonly infected site, followed by mitral valve. Diagnosis was set with a transthoracic ultrasound in 55.2%, while the diagnosis was set at autopsy in 16.7%. Fever and heart failure were the most common clinical presentations. Aminoglycosides, vancomycin, and cephalosporins were the antimicrobials most frequently used for treatment. Clinical cure was noted in 68.2%, while overall mortality was 41.4%. This systematic review thoroughly describes IE in patients with liver cirrhosis and provides information on epidemiology, clinical presentation, treatment and outcomes.


A new para-quinone-type flavan from the leaves of Ilex centrochinensis and its anti-inflammatory activities.
A new para-quinone-type flavan, (2S)-7-methoxy-3',4'-dihydroxy-5,8-quinoflavan (1), together with three known compounds, were isolated from the leaves of Ilex centrochinensis. Their structures were elucidated by detailed spectroscopic analyses for new structure and in comparison with published data for known compounds. Moreover, the new compound was evaluated its cytotoxic and anti-inflammatory activities in vitro on LPS induced RAW 264.7 cells and the results showed that 1 has promising anti-inflammatory activities.


Is aortography in lower limb ischaemia still abused?
A study in 1980 revealed that 38% of aortograms performed in a series had been referred for inappropriate reasons and only 49% had been clearly indicated. Recommendations were made to reduce the number of inappropriate investigations. An audit has been carried out of the aortography referrals made in this unit recently. This has shown that, despite changes in the management of peripheral vascular disease in the intervening years, by following the recommendations made in the previous paper, the number of inappropriate aortograms has been reduced to a minimum. The recommendations are endorsed.


Tuberculous meningitis in the southwest United States: a community-based study.
This community-based study analyzed 54 patients with definite or probable tuberculous meningitis (TBM) in New Mexico from 1970 through 1990. Patients ranged in age from 4 months to 86 years. The highest age-specific incidence occurred in the elderly, but 22% of patients were less than 10 years old. Native American patients were overrepresented. Patients were as likely to live in small towns as in large urban cities. Symptoms were present for a median of 13 days before admission. The majority of patients had fevers, headache, stiff neck, and mental changes, such as confusion or lethargy. No patient was admitted comatose. Focal neurologic signs were present in 33%. Laboratory testing found hyponatremia in 79%, pulmonary infiltrates on chest x-ray in 40%, ventricular dilatation on CT or MRI in 52%, and tuberculomas in 16%. PPD skin tests were positive in 64%. CSF cultures grew Mycobacterium tuberculosis in 50%, but colony counts were always lower than 10(2)/ml. As a consequence, acid-fast stains of CSF sediment were reported as positive in only 4%. Six patients were not diagnosed during the hospitalization and died of complications. Twenty-three percent of patients who were appropriately treated also died of complications during the initial hospitalization. Tuberculous meningitis continues to be an important disease in small communities, and affects all ages and ethnic and socioeconomic backgrounds.


Juvenile Hypothyroidism: A Clinical Perspective from Eastern India.
Juvenile hypothyroidism (JH) can have deleterious effects on growth, pubertal development, and scholastic performance of children. In India, there is a paucity of data on acquired hypothyroidism in children, in contrast to congenital hypothyroidism. Our objective was to assess the profile of JH in a referral clinic from eastern India. For this study, 100 patients with documented acquired hypothyroidism (subclinical and overt) (aged <18 years), from eastern India, were evaluated retrospectively. Evaluation included history as well as clinical, biochemical, and ultrasonography parameters. Out of the 100 participants, 74% had overt hypothyroidism (OH), while 26% had subclinical hypothyroidism (SCH). The majority of the participants were females (66%). The mean age at detection was 8.95 ± 3.96 years in the SCH group and 8.38 ± 3.29 years in the OH group. A family history of thyroid disorder and/or goiter was present in 35% of the patients. Goiter was the most common presentation in both SCH and OH, with overall prevalence of 58%. Height below 3rd percentile was significantly higher (28%) in OH group compared to 4% in SCH group. Five percent of OH subjects were obese. Worsening school performance was reported in only 9% of subjects. Only 4% (all males) presented with delayed puberty, while one female (1%) presented with precocious puberty. Sixty-four percent of OH group were TPOAb positive compared to only 15% in SCH group. Five percent of our study population had type-1 diabetes mellitus (T1DM) and 7% had Down syndrome (DS). In our study, JH showed significantly higher female preponderance and TPOAb positivity in OH group, in comparison to SCH group. Family history of thyroid disorder and/or goiter was present in a significant proportion of patients. Goiter was the most common presentation of JH. Height deceleration, weight gain, and fatigue were the other common presentations. Prevalence of short stature was significantly higher in OH group. Interestingly, in contrast to prevalent notion, only 5% of OH were obese and worsening school performance was observed to be rare. Puberty disorders (both delayed and precocious) may occur in JH as seen here. Because of strong association, those with T1DM or DS should be screened for JH and vice versa in TIDM.


Antibody response to measles and rubella vaccine by children with HIV infection.
To determine the immunogenicity of the measles and rubella components of the measles, mumps, and rubella virus (MMR) vaccine in human immunodeficiency virus (HIV)-infected children, we compared their response to that of uninfected controls. Sera were collected from HIV-infected patients and HIV seroreverters followed in our clinic and tested as close to 2 months post-MMR vaccination as possible. Specific IgG to both rubella and measles were measured by enzyme-linked immunosorbent assay. Of 20 children with HIV, 11 responded with adequate levels of antibody to measles. In the seroreverters, 12 of 13 responded. Of the measles responders, the median antibody level was significantly lower in the HIV-infected group than in the seroreverter group. In addition, HIV-infected responders tested at 9-15 months after vaccination demonstrated a significant decline in measles antibody levels. Although there was not a difference between the two cohorts in the proportion of patients who responded to the rubella component of the vaccine, there was a significant difference in the median antibody level of the responders of the two groups. We did not find a statistical difference in CD4 counts between responders and nonresponders. Alternate strategies will need to be established to prevent measles in HIV-infected children.


Sensitivity of the GEPARD Patient Questionnaire to Identify Psoriatic Arthritis in Patients with Psoriasis in Daily Practice: The GEPARD-Life Study.
Early detection of psoriatic arthritis (PsA) remains a challenge in clinical practice. Tools such as the German Psoriasis Arthritis Diagnostic (GEPARD) questionnaire have been developed for this purpose. The aim of this study was to determine the performance of the GEPARD questionnaire in the detection of PsA in psoriasis patients following rheumatology evaluation in daily clinical practice in Germany. This was a multicenter study involving 59 dermatology units (university/general hospital/office based), and the GEPARD questionnaire was distributed to psoriasis patients. Patients who had a sum score of ≥4 positive answers were referred to a rheumatologist for evaluation of PsA. We recruited 1,512 patients, of whom approximately 50% were referred. One third of the referred patients were classified as having PsA after rheumatological assessment. Rates of PsA in university/general hospital settings were higher than those observed in a doctor's office-based setting (43.7 vs. 25.8%). The GEPARD questionnaire demonstrated easy screening of psoriasis patients for PsA.


TomoFlow: Analysis of Continuous Conformational Variability of Macromolecules in Cryogenic Subtomograms based on 3D Dense Optical Flow.
Cryogenic Electron Tomography (cryo-ET) allows structural and dynamics studies of macromolecules in situ. Averaging different copies of imaged macromolecules is commonly used to obtain their structure at higher resolution and discrete classification to analyze their dynamics. Instrumental and data processing developments are progressively equipping cryo-ET studies with the ability to escape the trap of classification into a complete continuous conformational variability analysis. In this work, we propose TomoFlow, a method for analyzing macromolecular continuous conformational variability in cryo-ET subtomograms based on a three-dimensional dense optical flow (OF) approach. The resultant lower-dimensional conformational space allows generating movies of macromolecular motion and obtaining subtomogram averages by grouping conformationally similar subtomograms. The animations and the subtomogram group averages reveal accurate trajectories of macromolecular motion based on a novel mathematical model that makes use of OF properties. This paper describes TomoFlow with tests on simulated datasets generated using different techniques, namely Normal Mode Analysis and Molecular Dynamics Simulation. It also shows an application of TomoFlow on a dataset of nucleosomes in situ, which provided promising results coherent with previous findings using the same dataset but without imposing any prior knowledge on the analysis of the conformational variability. The method is discussed with its potential uses and limitations.


Optimisation of ion trap parameters for the quantification of chlormequat by liquid chromatography/mass spectrometry and the application in the analysis of pear extracts.
Optimisation of the activation parameters for ion trap mass spectrometric analysis of the chlormequat cation using simplex optimisation enabled the product ion (m/z 58) response to be improved 1000-fold. A comparison of the sensitivity of the optimised ion trap mass spectrometer with that of a triple quadrupole mass spectrometer for liquid chromatography/tandem mass spectrometry (LC/MS/MS) showed that similar limits of detection (LODs) could be achieved. For the MS/MS transition of the (35)Cl precursor to the most abundant product, LODs were 0.8 ng cation mL(-1) (0.004 mg cation kg(-1) pear equivalent) and 1.0 ng cation mL(-1) (0.005 mg cation kg(-1) pear equivalent) on the triple quadrupole and ion trap instrument, respectively.


[Efficacy of nasal bi-level positive airway pressure ventilation in a patient with olivo-ponto-cerebellar atrophy suffering from sleep apnea syndrome].
Sleep apnea with neuromuscular disorders has been successfully treated with bi-level positive airway pressure ventilation (BiPAP), which, unlike continuous positive airway pressure ventilation (CPAP), creates pressure difference between expiratory and inspiratory phases. Hence if the respiration of patients stops longer than a pre-set duration, BiPAP can automatically force them to breath through a nasal mask. We report a 60-year-old woman with olivo-ponto-cerebellar atrophy (OPCA), whose mixed-type sleep apnea was difficult to treat with conventional CPAP. We therefore tried BiPAP on this patient at night. Nocturnal CO2 retention was nearly resolved, and unexpectedly daytime PaCO2 was also corrected with marked improvement of daytime somnolence. BiPAP is totally non-invasive, and may be one of the most effective treatments in patients with OPCA suffering from sleep apnea.


Laser and radiofrequency ablations for benign and malignant thyroid tumors.
A growing body of evidence is being published regarding the safety and efficacy of minimally invasive image-guided ablation techniques. While clinical applications of these techniques are increasing, international societies have started to publish treatment guidelines and to make efforts to standardize both terminology and reporting criteria for image-guided thyroid ablations. Laser ablation and radiofrequency ablation (RFA) are among the most common ablation techniques either for benign and malignant thyroid nodules. Unlike laser ablation and RFA in the treatment of benign thyroid nodules, where safety and efficacy have been widely demonstrated, evidence regarding local tumor control of thyroid malignancies is still limited. However, preliminary results are encouraging and image-guided thermal ablation techniques can be considered a valid alternative to surgery for the treatment of benign thyroid nodules and recurrent thyroid cancers. This review evaluates the basic concept of RFA and laser ablations, their techniques, clinical outcomes, and complications based on the suggestions of several society guidelines. Multidisciplinary collaboration remains critical to identify patients which may benefit from minimally invasive image-guided thermal ablations, especially if surgery or radioiodine therapy are not feasible options.


Sebaceous gland carcinoma and mammary gland carcinoma in an African hedgehog (Ateletrix albiventris).
A sebaceous carcinoma was diagnosed, together with a mammary carcinoma, in an adult African hedgehog (Atelerix albiventris). The first neoplasm was located in the subcutaneous tissue of the neck and extended towards the axillary area of the chest. The second was located in the subcutaneous left caudal abdominal region. The purpose of this paper is to report the histopathologic and ultrastructural features of these neoplasms. Although there is little information about diseases affecting this species, it is known that neoplastic disorders are fairly common in African hedgehogs. The mammary carcinoma is considered to be the most common neoplasm in these animals; however, the presentation of sebaceous carcinoma is rare. In hedgehogs, the simultaneous presence of two neoplasms is common, which is why special attention should be paid to the presentation of other tumors during the early detection of a neoplastic process as this will greatly facilitate the optimal treatment and improve the long-term prognosis of affected animals.


Losses, Gains, and Changes to the Food Environment in a Rural Kentucky County during the COVID-19 Pandemic.
The COVID-19 pandemic has caused alterations to be made in the way many people access, prepare, and consume food. Rural communities are particularly impacted due to pre-existing structural vulnerabilities, i.e., poverty, lack of infrastructure, and limited fresh food options. This study aimed to characterize experiences of one rural Appalachian community's changes to the food environment during the pandemic. In April 2021, six focus groups were conducted with residents of Laurel County, Kentucky. Using grounded theory, we identified losses, gains, and overall changes to the community food environment since the onset of COVID-19. Seventeen Laurel Countians (17 female; ages 30-74) participated in the six focus groups. Three main themes emerged regarding food environment changes-(1) modifications of community food and nutrition resources, (2) expansion and utilization of online food ordering, and (3) implications of the home food environment. Rural communities faced considerable challenges during the COVID-19 pandemic, in part, due to gaps in existing infrastructure and loss of pre-existing resources. This study illustrates the complexity of changes occurring during COVID-19. Using the preliminary data obtained, we can better understand pre-existing issues in Laurel County and suggestions for future programming to address the inequitable access and response during public health emergencies and beyond.


Restricted alpha- and beta-adrenoceptor affinity of sulfoconjugated catecholamines in human mononuclear leukocytes, platelets, and fat cells and reduction of the postreceptor mechanisms.
The physiologic significance of the racemic 3-O-sulfate esters of epinephrine (EPI-3-O-S) and norepinephrine (NE-3-O-S) as well as 4-O-sulfoconjugated dopamine (DA-4-O-S) was evaluated. For this purpose these conjugated catecholamines (CA) were synthesized and investigated with respect to their alpha 2- and beta 2-adrenoceptor affinities and their biological activity in three different human cell systems: in mononuclear leukocytes (MNL), platelets, and fat cells. The unequivocal identification and the minimal degree of contamination of the synthesized sulfoconjugates with free CA was proved by 1H-NMR and by high-performance liquid chromatography with amperometric detection (HPLCA) respectively. In isolated human MNL, beta-adrenoceptor affinities of these conjugated CA were determined in competition experiments with the lipophilic nonspecific radioligand (-) 125I-cyanopindolol (ICYP) and, in addition, with the hydrophilic ligand 3H-CGP12177. With both ligands the affinity constants (KD) of the sulfoconjugated CA under investigation were about 100- to 1000-fold higher when compared with the respective free amines. Moreover, these sulfoconjugated CA per se induced no intracellular production of cyclic adenosine monophosphate (cAMP) in MNL. In comparison with the free amines, metanephrine (MN) and normetanephrine (NMN) showed a highly reduced competitive potency on the MNL beta-adrenoceptors labelled with 3H-CGP or ICYP. The KD values for MN and NMN in competition studies with ICYP were 10- and 5-fold higher than in those with 3H-CGP respectively, indicating a restricted access of MN and NMN to intracellular receptors. The adenylate cyclase system was not stimulated at all by MN or by NMN. In human platelets EPI-3-O-S and NE-3-O-S neither competed with the specific alpha 2-adrenoceptor antagonist 3H-yohimbine nor elicited any aggregation response at all. MN and NMN exhibited an about 40-fold reduced affinity for alpha 2-adrenoceptors in platelets when compared with the respective free amines and elicited no aggregation response at all. However, in the presence of MN and NMN the EPI- and NE-induced platelet aggregation was dose-dependently attenuated. These findings reveal an alpha 2-adrenoceptor antagonistic potency of MN and NMN. In human adipocytes EPI-3-O-S and NE-3-O-S were 100- to 1000-fold less potent to inhibit lipid mobilization via alpha 2-adrenoceptors as well as to stimulate the beta-adrenoceptor mediated lipolysis when compared with free CA.


GIP1 and GIP2 Contribute to the Maintenance of Genome Stability at the Nuclear Periphery.
The maintenance of genetic information is important in eukaryotes notably through mechanisms occurring at the nuclear periphery where inner nuclear membrane proteins and nuclear pore-associated components are key factors regulating the DNA damage response (DDR). However, this aspect of DDR regulation is still poorly documented in plants. We addressed here how genomic stability is impaired in the gamma-tubulin complex component 3-interacting protein (gip1gip2) double mutants showing defective nuclear shaping. Using neutral comet assays for DNA double-strand breaks (DSBs) detection, we showed that GIP1 and GIP2 act redundantly to maintain genome stability. At the cellular level, γ-H2AX foci in gip1gip2 were more abundant and heterogeneous in their size compared to wild-type (WT) in root meristematic nuclei, indicative of constitutive DNA damage. This was linked to a constitutive activation of the DDR in the gip1gip2 mutant, with more emphasis on the homologous recombination (HR) repair pathway. In addition, we noticed the presence of numerous RAD51 foci which did not colocalize with γ-H2AX foci. The expression of GIP1-GFP in the double mutant rescued the cellular response to DNA damage, leading to the systematic colocalization of RAD51 and γ-H2AX foci. Interestingly, a significant proportion of RAD51 foci colocalized with GIP1-GFP at the nuclear periphery. Altogether, our data suggest that GIPs may partly contribute to the spatio-temporal recruitment of RAD51 at the nuclear periphery.


Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer.
To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. In the majority of the tumor samples, TGF-β1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores ≥ 7 when compared to patients with Gleason scores < 7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3% had poor prognostic features. TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.


"Mr. Database" : Jim Gray and the History of Database Technologies.
Although the widespread use of the term "Big Data" is comparatively recent, it invokes a phenomenon in the developments of database technology with distinct historical contexts. The database engineer Jim Gray, known as "Mr. Database" in Silicon Valley before his disappearance at sea in 2007, was involved in many of the crucial developments since the 1970s that constitute the foundation of exceedingly large and distributed databases. Jim Gray was involved in the development of relational database systems based on the concepts of Edgar F. Codd at IBM in the 1970s before he went on to develop principles of Transaction Processing that enable the parallel and highly distributed performance of databases today. He was also involved in creating forums for discourse between academia and industry, which influenced industry performance standards as well as database research agendas. As a co-founder of the San Francisco branch of Microsoft Research, Gray increasingly turned toward scientific applications of database technologies, e. g. leading the TerraServer project, an online database of satellite images. Inspired by Vannevar Bush's idea of the memex, Gray laid out his vision of a Personal Memex as well as a World Memex, eventually postulating a new era of data-based scientific discovery termed "Fourth Paradigm Science". This article gives an overview of Gray's contributions to the development of database technology as well as his research agendas and shows that central notions of Big Data have been occupying database engineers for much longer than the actual term has been in use.


Risk for Invasive Streptococcal Infections among Adults Experiencing Homelessness, Anchorage, Alaska, USA, 2002-2015.
The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002-2015. We used data from the Centers for Disease Control and Prevention's Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.


Effects of heat stress on serum progesterone in cyclic ewes and on progesterone and cortisol response to ACTH in ovariectomized ewes.
The daily mean of serum progesterone in cyclic ewes (N = 5) as well as the profile characteristics of progesterone and cortisol in response to an acute single dose (5 i.u./kg liveweight 0.75) of adrenocorticotrophic hormone (ACTH) into ovariectomized ewes (N = 4) was investigated during exposure to a constant thermoneutral temperature of 18 +/- 1 degree C or to a daily cyclic heat stress temperature of 18 degrees C-35 degrees C-18 degrees C, in an environmental chamber. Serum collected daily from the cyclic ewes was assayed for progesterone, while serum collected more frequently for 10 h, on the 14th day of exposure to the respective temperature, from the ovariectomized ewes was assayed for progesterone and cortisol by RIAs. In cyclic ewes, heat stress increased the area under the daily progesterone curve (P less than 0.09) but had no effect on progesterone concentration after the regression of the CL. In ovariectomized ewes, ACTH significantly elevated the response of both cortisol and progesterone (r = 0.75, P less than 0.001) within 10-15 min of injection. In the ovariectomized ewes and during heat stress, the responses of progesterone and cortisol to ACTH were characterized by an initial acute rise, a transient drop, a steep elevation and a gradual but prolonged decline. During thermoneutral temperatures, this biphasic response pattern was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice.
Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM). In addition, latent infections with EBV are associated with nasopharyngeal carcinoma (NPC) and Burkitt's Lymphoma (BL). Antibodies to several EBV-encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV-encoded proteins in the etiology of these and other EBV-associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen-stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon-gamma after re-stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase-treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease.


[Comparative study of continuous epidural analgesia versus intermittent, patient-controlled, epidural analgesia during labor].
To assess the analgesic efficacy and the incidence of side effects of three procedures of epidural analgesia during labor. One hundred and one nulliparous pregnant women at term with cephalic presentation were randomly allocated to 3 groups (A: 31, B: 35, C: 35). Group A was given an initial dose of 8 ml bupivacaine 0.25% (20 mg) with epinephrine 1/200,000 and 50 micrograms fentanyl followed by a continuous infusion of 8 ml/h bupivacaine 0.125% (10 mg/h) with epinephrine 1/400,000. The initial dose in group B was 10 ml bupivacaine 0.125% (12.5 mg) with epinephrine 1/400,000 and 50 micrograms fentanyl followed by a continuous infusion of 12 ml/h bupivacaine 0.0625% (7.5 mg/h) with epinephrine 1/800,000 and 12 micrograms/h fentanyl. In group C the initial dose was the same as for group A, but maintenance was provided through a patient-controlled (PCA) system with 5 ml bupivacaine 0.25% (12.5 mg) and epinephrine 1/200,000 set for a minimum interval of 1 h. If analgesia was inadequate all patients could receive top-ups of 5 ml bupivacaine 0.25% (12.5 mg) with epinephrine 1/200,000. Quality of analgesia was similar in all three groups. We found no significant differences in level of sensory/motor blockade, hemodynamic changes, side effects or type of delivery. The total dose of bupivacaine was highest in group A, whereas group B received the higher total dose of fentanyl. The number of Apgar scores under 8 was highest in group A, although the scores rose within 5 min of delivery in all cases. We believe that the protocol of choice is the one used with group B (initial dose of 10 ml bupivacaine 0.125% + epinephrine 1/400,000 + 50 micrograms fentanyl followed by 12 ml/h bupivacaine 0.0625% + epinephrine 1/800,000 + 12 mu cg/h fentanyl in continuous infusion). The use of PCA systems with our unscreened patients yielded no advantages over the procedure used with group B.


Focus on primary care. Thyroid function and dysfunction in women.
All forms of thyroid disease are more common in women. The reason for this gender predilection has not been entirely elucidated but may relate to the closely intertwined relationship between thyroid function and the female reproductive axis. Thyroid dysfunction influences both menstrual function and fertility, likely through changes in sex hormone levels, gonadotropin release, and possibly ovarian function. Similarly, alterations in reproductive physiology can modulate thyroid function. In such settings as pregnancy, when sex hormone levels fluctuate markedly, variations in thyroid function occur frequently. For the clinician, understanding when such alterations require intervention is critical. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader will be able to describe the abnormalities of the female reproductive axis associated with both hypo- and hyperthyroidism, to summarize how female sex hormones affect thyroid function, and to explain the effects of pregnancy on thyroid conditions.


Effects of spontaneous recurrent seizures on cognitive function via modulation of SNAREs expression.
To explore whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complexes are involved in cognitive dysfunction induced by spontaneous recurrent seizures (SRS). An animal model of epilepsy was established by intraperitoneal injection of kainic acid (KA). Following the onset of SRS, the rats were divided into control group, KA-SRS group, KA+SRS group and KA+SRS+VAP group. Morris water maze and open field test were conducted to evaluate the cognitive function. Protein and mRNA levels of SNAREs complex were measured by Western-blot and RT-PCR, respectively. Besides, the Ca2+ concentration in the hippocampus was also detected. A delayed escape latency and a reduced number of platform crossings were found in the KA+SRS group. Meanwhile, a longer moving distance and time spent in central area were also observed during the open field test. Besides, the Ca2+ concentration in the hippocampus of the KA+SRS group was markedly increased. However, when compared with the KA+SRS group, all indices in the KA+SRS+VAP group were markedly improved. Moreover, the SNARE complexes in the hippocampus of the KA+SRS group were significantly increased when compared with both control group and KA+SRS+VAP group. Results of our study demonstrated that the cognitive dysfunction caused by SRS may be attributed to the modulation expression of SNARE complexes.


Higher-Order Band Topology in Twisted Moiré Superlattice.
The two-dimensional (2D) twisted bilayer materials with van der Waals coupling have ignited great research interests, paving a new way to explore the emergent quantum phenomena by twist degree of freedom. Generally, with the decreasing of twist angle, the enhanced interlayer coupling will gradually flatten the low-energy bands and isolate them by two high-energy gaps at zero and full filling, respectively. Although the correlation and topological physics in the low-energy flat bands have been intensively studied, little information is available for these two emerging gaps. In this Letter, we predict a 2D second-order topological insulator (SOTI) for twisted bilayer graphene and twisted bilayer boron nitride in both zero and full filling gaps. Employing a tight-binding Hamiltonian based on first-principles calculations, three unique fingerprints of 2D SOTI are identified, that is, nonzero bulk topological index, gapped topological edge state, and in-gap topological corner state. Most remarkably, the 2D SOTI exists in a wide range of commensurate twist angles, which is robust to microscopic structure disorder and twist center, greatly facilitating the possible experimental measurement. Our results not only extend the higher-order band topology to massless and massive twisted moiré superlattice, but also demonstrate the importance of high-energy bands for fully understanding the nontrivial electronics.


Purification and characterization of an erythromycin esterase from an erythromycin-resistant Pseudomonas sp.
An erythromycin esterase (molecular mass 51200 Da) was purified from Pseudomonas sp. GD100, which was isolated from a salmon hatchery sediment sample from Washington State. The pI of the protein was 4.5-4.8. The enzyme was inhibited by 1 mM mercuric acid, and had the substrate specificity for structurally related 14-membered macrolides, which decreased in the order of oleandomycin, erythromycin A and erythromycin A enol ether. The activity for erythromycin A varied with temperature, but the effect of pH was minimal at pH 6.0-9.0. The half-life of the enzyme was estimated to be 8.9 h at 35 degrees C and 0.23 h at 55 degrees C, and the activation energy of the catalytic reaction of erythromycin A was estimated at 16.2 kJ mol(-1).


Ions modify the strength of interaction of diquat and paraquat with some proteins and cellulose.
The interaction of the bipyridylium herbicides diquat and paraquat with the proteins gliadin and human serum albumin (HSA) as well as with cellulose and the effect of various ions on the strength of interaction were studied by charge-transfer chromatography. Both compound showed very similar behaviour. The ions decreased in each case the strength of interaction, the effect depended nonlinearly on the ion concentration and was of saturation character. Gliadin showed the weakest interaction. HSA binds the bipyridylium compounds in an ion-dependent manner, the strength of interaction is higher than that of cellulose at higher ion concentration. This finding indicates an ion-mediated interaction of unknown character between the bipyridylium herbicides and HSA.


Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies.
BRAF mutations are present in two thirds of cutaneous melanomas and many of the rest have NRAS mutations. However, cutaneous melanoma is a heterogeneous disease with many clinicopathologic subtypes. Of these, the majority fits into four categories: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma (ALM). Thus far, there is very limited data combining BRAF and NRAS mutation analysis to explore differences between cutaneous melanoma subtypes. The aim of this study was to address this issue. The frequency of BRAF and NRAS hotspot mutations, in exons 15 and 2, respectively, was assessed in 59 cutaneous melanomas comprising superficial spreading, nodular, lentigo maligna, and ALM using single-strand conformational polymorphism and RFLP-PCR analysis. Only 2 of 21 (9.5%) ALM showed BRAF exon 15 mutation compared with 9 of 14 (64.3%) superficial spreading malignant melanomas, 4 of 11 (36.4%) nodular melanomas, and 7 of 13 (53.4%) lentigo maligna melanomas (P < 0.01). However, our key finding is that the combined analysis of BRAF exon 15 and NRAS exon 2 showed that there were no significant differences in the overall mutation frequency between subtypes. In particular, 9 of 19 (47.4%) ALM without BRAF exon 15 mutation had an NRAS exon 2 mutation. We show that the overall BRAF/NRAS frequency in mutation hotspots is not significantly different among cutaneous melanoma subtypes. These data show that mitogen-activated protein kinase pathway activation may be important in all major subtypes of cutaneous melanoma, although the mechanism by which this is achieved varies.


An overview of the use of anti-tuberculous drugs in Uganda and Hong Kong.
Anti-tuberculous (Anti-TB) chemotherapy in Uganda is outlined. Its pattern of use and the subsequent shortcomings have prompted the need for the present review. A collateral comparison to that of Hong Kong was run to emphasize the correlation of anti-TB chemotherapy with economic development and regional variation in the population of the two areas. Tuberculosis of the central nervous system (CNS) has a high fatality rate. In the search for a more comprehensive anti-TB dosage regimen, the difficulty in treating tuberculosis of the CNS has attracted special attention with emphasis on the fate of anti-TB drugs across the meninges. The choice of a method for drug analysis in routine therapeutic drug monitoring for a country is likewise determined by factors similar to those for the anti-TB regimen. Uganda needs an inexpensive, precise and selective method for TB treatment tailored to its financial and manpower resources.


Sexual compulsivity, erectile dysfunction, and suicidality among male survivors of military sexual violence.
Although military sexual trauma (MST) is associated with an increased risk of suicide, suicide attempts, and suicidal ideation among service members and veterans, there is limited knowledge regarding the mechanisms of MST and suicidality among men. The current study examined whether MST was associated with sexual compulsivity and/or erectile dysfunction and if these, in turn, explained elevated suicidal thoughts and the likelihood of engaging in future suicidal behavior after accounting for mental health, military, and demographic characteristics. Service members and veterans who reported their gender as male (N = 508) were recruited via social media and completed online self-report measures assessing MST, erectile dysfunction, sexual compulsivity, suicidal ideation frequency, and the likelihood of engaging in future suicidal behavior. Path analysis was used to examine the study hypotheses. In total, 67 participants (13.2%) reported a history of MST; of these individuals, 27 (40.3%) reported suicidal ideation in the past 12 months, and 29 (43.9%) reported an increased likelihood of engaging in future suicidal behavior. MST was associated with increased sexual compulsivity, which, in turn, predicted more frequent suicidal ideation as well as a higher self-reported likelihood of engaging in future suicidal behavior. MST was associated with higher levels of erectile dysfunction, but erectile dysfunction was not associated with suicidal ideation in the adjusted model. Although the data were cross-sectional, precluding determinations of causality, the results support assessing and intervening with regard to sexual compulsivity to mitigate the risk for suicide-related outcomes among men who experience MST.


On the relation between time-dependent and variational density functional theory approaches for the determination of excitation energies and transition moments.
It is shown that it is possible to derive the basic eigenvalue equation of adiabatic time-dependent density functional theory within the Tamm-Dancoff approximation (TD-DFT/TD) from a variational principle. The variational principle is applied to the regular Kohn-Sham formulation of DFT energy expression for a single Slater determinant and leads to the same energy spectrum as TD-DFT/TD. It is further shown that this variational approach affords the same electric and magnetic transition moments as TD-DFT/TD. The variational scheme can also be applied without the Tamm-Dancoff approximation. Practical implementations of TD-DFT are limited to second order response theory which introduces errors in transition energies for charge transfer and Rydberg excitations. It is indicated that higher order terms can be incorporated into the variational approach. It is also discussed how the current variational method is related to traditional DFT schemes based on variational principles such as DeltaSCF-DFT, and how they can be combined.


Lymphoepithelial - Like Carcinoma with Papillary Transitional Cell Carcinoma of the Urinary Bladder Associated with Carcinoma in situ Changes of the Urothelium; A Case Report and Review of Literature.
Lymphoepithelial - like carcinoma, is rarely recognized in the urinary bladder and less commonly occurs with papillary transitional cell carcinoma i.e. mixed pattern. Also, less uncommon is the occurrence of carcinoma in situ changes in the adjacent urothelium of these tumors. Here, a case of lymphoepithelial - like carcinoma and papillary transitional cell carcinoma associated with carcinoma in situ changes of urothelium of the urinary bladder has been reported the prognosis of this type of malignancy as well as its management will be discussed. Meanwhile, immunohistochemical stains have been carried out to differentiate it from lymphoma of the urinary bladder and the findings will be discussed.


Inverted papilloma of the urinary bladder.
Inverted papillomas are rare in the lower urinary tract. It is a histologically benign tumor with low grade malignant potential. Association with transitional cell carcinoma has also been reported. Eight cases of inverted papilloma of the urinary bladder were diagnosed at this hospital between November 1990 and May 1994. There were one female and seven males with an average age of 63.5 years. We analyze their clinical presentations, histological findings and the outcome of treatments. Four patients presented with hematuria, and four with obstructive symptoms. Four were solid pedunculated tumors; three were papillary pedunculated; and one was a papillary sessile tumor. All tumors were solitary with four located in the bladder neck, two in the lateral wall, one in the interureteral ridge, and one in the trigonal area. A 77-year-old man whose tumor coexisted with an infiltrative transitional cell carcinoma was treated with partial cystectomy. The other seven patients were treated by transurethral resection. All the tumors were of the trabecular type and three of them (37.5%) harbored calcium oxalate crystals. There was no evidence of recurrence in a median follow-up of 18 months. Inverted papillomas of urinary bladder are benign tumors, which can be treated successfully by transurethral resection and fulguration of tumor bed. However, precautionary studies are necessary to exclude the coexistence of malignancy and annual follow-up with cystourethroscopy is mandatory.


Effect of the Oxygen Concentration and Temperature on Thermal Decomposition of N2O in an Inert Gas.
Nitrous oxide (N2O) is one of the greenhouse gases that contribute to global warming. But, there are few methods for controlling N2O directly. It is essential to reduce N2O to solve environmental problems. In this study, we investigate the O2 concentration dependence of N2O decomposition under an argon-based gas mixture in a high-temperature thermal reactor. The gas concentrations are calculated using CHEMKIN. The results confirm that more N2O is converted to N2 or NO at lower O2 concentrations. Therefore, the conversion process is hindered by increasing the O2 concentration. We propose a modified parameter of N2O decomposition, and it is employed in the CHEMKIN calculations. With the modified parameter, the experimental results are in a similar tendency to the calculated results.