Growth and high-valued products accumulation characteristics of microalgae in saline-alkali leachate from Inner Mongolia.
In this study, the growth and high-valued products accumulation characteristics of three common high-valued microalgae (Chlorella sp. HQ, Scenedesmus sp. LX1, and Chlorella vulgaris) in saline-alkali leachate were compared to select the species with greatest utilization potential. The results showed that after 28 days of cultivation, among three microalgae, Chlorella sp. HQ grew best with its maximum density at peak of 1.16 × 107 cells mL-1 and lipid production per unit cell (0.047 ± 0.006 × 10-7 mg cell-1) and lipid content (18.18 ± 3.14%) were largest. The triacylglycerol (TAG) yield and content of Scenedesmus sp. LX1 were the highest, reaching 0.005 ± 0.000 × 10-7 mg cell-1 and 19.74 ± 2.53%, respectively, which was slightly higher than those of Chlorella sp. HQ. According to comprehensive comparison, Chlorella sp. HQ was most suitable to grow in the saline-alkali leachate in terms of algal density, lipid yield, and content. The potential comparison and effects of salinity on the high-valued products accumulation of Chlorella sp. HQ compared with those in SE standard medium, reclaimed water, and tap water were further carried out. It was found that the density order of Chlorella was saline-alkali leachate > SE medium > reclaimed water > tap water. And the Chlorella density in the leachate with a salinity of 0.14% was greater than the other three salinities (0.32%, 0.45%, and 0.6%) at the end of cultivation. While the maximum lipid yield per unit cell and lipid content of Chlorella occurred in the salinity of 0.6%, which indicated that high salinity promoted the accumulation of lipid. Furthermore, other high-valued products (including starch, protein, total sugar, and photosynthetic pigments) accumulation characteristics were analyzed and found that they were all superior than those in SE medium. And with the salinity decreased, the microalgal protein and starch contents decreased. The contents of photosynthetic pigment and total sugar reached a maximum at salinities of 0.32% and 0.45%, respectively.


Intestinal epithelial ablation of Pit-2/Slc20a2 in mice leads to sustained elevation of vitamin D3 upon dietary restriction of phosphate.
Several Na+ -dependent phosphate cotransporters, namely NaPi-IIb/SLC34A2, Pit-1/SLC20A1 and Pit-2/SLC20A2, are expressed at the apical membrane of enterocytes but their contribution to active absorption of phosphate is unclear. The aim of this study was to compare their pattern of mRNA expression along the small and large intestine and to analyse the effect of intestinal depletion of Pit-2 on phosphate homeostasis. Intestinal epithelial Pit-2-deficient mice were generated by crossing floxed Pit-2 with villin-Cre mice. Mice were fed 2 weeks standard or low phosphate diets. Stool, urine, plasma and intestinal and renal tissue were collected. Concentration of electrolytes and hormones, expression of mRNAs and proteins and intestinal transport of tracers were analysed. Intestinal mRNA expression of NaPi-IIb and Pit-1 is segment-specific, whereas the abundance of Pit-2 mRNA is more homogeneous. In ileum, NaPi-IIb mRNA expression is restricted to enterocytes, whereas Pit-2 mRNA is found in epithelial and non-epithelial cells. Overall, their mRNA expression is not regulated by dietary phosphate. The absence of Pit-2 from intestinal epithelial cells does not affect systemic phosphate homeostasis under normal dietary conditions. However, in response to dietary phosphate restriction, Pit-2-deficient mice showed exacerbated hypercalciuria and sustained elevation of 1,25(OH)2 vitamin D3 . In mice, the intestinal Na+ /phosphate cotransporters are not coexpressed in all segments. NaPi-IIb but not Pit-2 mRNA is restricted to epithelial cells. Intestinal epithelial Pit-2 does not contribute significantly to absorption of phosphate under normal dietary conditions. However, it may play a more significant role upon dietary phosphate restriction.


Identification of a novel gene product expressed by Trichinella spiralis that binds antiserum to Sp2/0 myeloma cells.
To obtain novel antigen genes for use as an anti-tumor vaccine, a Trichinella spiralis cDNA expression library was constructed from muscle larvae RNA and screened with sera from Balb/C mice injected with Sp2/0 myeloma cells. One positive clone was obtained after three rounds of immunoscreening of the cDNA expression library and was subsequently excised in vivo using the ExAssist helper phage with SOLR strain. A full-length gene was amplified using 5'-RACE technology and analyzed by BLAST, Protein Analysis System of ELM, and DNAStar Software. The sequencing results showed that the fragment was 569 bp in length and contained an open reading frame. It was predicted that the full-length gene encoded 136 amino acids. This gene, TS2, contained four putative N-Arg dibasic convertase (nardilysine) cleavage sites, one peptide C-terminal amidation site, and one glycosaminoglycan attachment site. Six antibody epitopes were predicted by bioinformatic analysis.


MR imaging of ischemic heart disease.
When ischemic heart disease (IHD) is suspected or confirmed, the primary imaging modality is echocardiography. When appropriate, complementary examinations can be performed. These include stress perfusion scintigraphy, cardiac catheterization, coronary angiography, and CT. MR imaging techniques have developed rapidly over the past several years, and MR imaging has the ability to delineate myocardial perfusion, ventricular function, and myocardial viability in a single examination. Although coronary MR angiography is promising, in recent years it has been supplanted as a noninvasive imaging modality by coronary CT angiography. The other capabilities of MR imaging suggest that it will be performed more and more frequently for the assessment of IHD.


Engagement Rules That Underpin DBL-DARC Interactions for Ingress of Plasmodium knowlesi and Plasmodium vivax Into Human Erythrocytes.
Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via cyclical invasion of host erythrocytes using dedicated receptor-ligand interactions. A family of erythrocyte-binding proteins from Plasmodium knowlesi (Pk) and Plasmodium vivax (Pv) attach to human Duffy antigen receptor for chemokines (DARC) via their Duffy binding-like domains (DBLs) for invasion. Here we provide a novel, testable and overarching interaction model that rationalizes even contradictory pieces of evidence that have so far existed in the literature on Pk/Pv-DBL/DARC binding determinants. We further address the conundrum of how parasite-encoded Pk/Pv-DBLs recognize human DARC and collate evidence for two distinct DARC integration sites on Pk/Pv-DBLs.


Diagnosis, imaging and anatomical classification of uterine fibroids.
Uterine leiomyomata, commonly referred to as fibroids, are often accompanied by symptoms common to many other pelvic conditions. The correct identification of myomata and the exclusion of other diseases, especially malignancies, are imperative when evaluating therapy options. A confident diagnosis of myomata may be aided by several imaging modalities. The selection of an imaging technique should include an evaluation of both the benefits and the costs associated with the procedure. Imaging can provide information regarding precise myomata location, which may, in turn, dictate treatment options. Myomata may be classified based upon position within the uterus, and may be further described by phase of degeneration. With the increasing popularity of uterine-conserving therapy, accurate diagnosis of myomata becomes even more important.


Patterns of spatial genetic structures in Aedes albopictus (Diptera: Culicidae) populations in China.
The Asian tiger mosquito, Aedes albopictus, is one of the 100 worst invasive species in the world and the vector for several arboviruses including dengue, Zika and chikungunya viruses. Understanding the population spatial genetic structure, migration, and gene flow of vector species is critical to effectively preventing and controlling vector-borne diseases. Little is known about the population structure and genetic differentiation of native Ae. albopictus in China. The aim of this study was to examine the patterns of the spatial genetic structures of native Ae. albopictus populations, and their relationship to dengue incidence, on a large geographical scale. During 2016-2018, adult female Ae. albopictus mosquitoes were collected by human landing catch (HLC) or human-bait sweep-net collections in 34 localities across China. Thirteen microsatellite markers were used to examine the patterns of genetic diversity, population structure, and gene flow among native Ae. albopictus populations. The correlation between population genetic indices and dengue incidence was also examined. A total of 153 distinct alleles were identified at the 13 microsatellite loci in the tested populations. All loci were polymorphic, with the number of distinct alleles ranging from eight to sixteen. Genetic parameters such as PIC, heterozygosity, allelic richness and fixation index (FST) revealed highly polymorphic markers, high genetic diversity, and low population genetic differentiation. In addition, Bayesian analysis of population structure showed two distinct genetic groups in southern-western and eastern-central-northern China. The Mantel test indicated a positive correlation between genetic distance and geographical distance (R2 = 0.245, P = 0.01). STRUCTURE analysis, PCoA and GLS interpolation analysis indicated that Ae. albopictus populations in China were regionally clustered. Gene flow and relatedness estimates were generally high between populations. We observed no correlation between population genetic indices of microsatellite loci in Ae. albopictus populations and dengue incidence. Strong gene flow probably assisted by human activities inhibited population differentiation and promoted genetic diversity among populations of Ae. albopictus. This may represent a potential risk of rapid spread of mosquito-borne diseases. The spatial genetic structure, coupled with the association between genetic indices and dengue incidence, may have important implications for understanding the epidemiology, prevention, and control of vector-borne diseases.


Alterations in Phase-Related Prefrontal Activation During Cognitive Tasks and Nicotinic α4β2 Receptor Availability in Alzheimer's Disease.
Evidence shows that the cholinergic system plays an important role in regulating working memory and that working memory-related prefrontal activation decreases with age and neuronal degeneration, such as Alzheimer's disease (AD). However, the relation between attention-related α4β2 nicotinic cholinergic function and task-induced prefrontal activation especially time course-related activation remains to be explored. We aimed to elucidate the relationship between changes in task-induced oxy-hemoglobin concentration (cerebral blood flow, CBF) in the prefrontal cortex and the availability of α4β2 nicotinic receptors in the brain of AD patients in light of their task performance. Eleven mild-to-moderate AD patients and eleven normal elderly subjects underwent the near-infrared spectroscopy during easy and difficult working memory tasks for estimating prefrontal CBF changes and positron emission tomography with the α4β2 tracer [18F]2FA-85380 ([18F]2FA) for measuring the α4β2 nicotinic receptor binding. Significant correlations between mean oxy-hemoglobin concentration in the channels with significant [group] main effects and prefrontal [18F]2FA binding were observed during the early easy task period in the normal group and during the late difficult task in the AD group. In addition, those prefrontal CBF responses were significantly correlated with not correct performance but the execution time to spend. The α4β2 nicotinic acetylcholine receptors in the prefrontal cortex play an important role in increasing prefrontal activation when attending to novel stimuli, irrespective of the accuracy of the outcome. A delay in the cholinergic-induced increase in prefrontal activation in AD patients might explain their delayed responses in the cognitive task.


Can skin disease cause neuropathic pain? A study in pachyonychia congenita.
Pachyonychia congenita (PC) is a rare skin disorder caused by an autosomal dominant mutation in one of five genes encoding keratin (K6a, K6b, K6c, K16 or K17; each defining one PC subtype). Pain is a prominent symptom, but its severity and type are poorly characterized. In total, 35 genotyped US patients with PC consented to clinical assessment including the quality of life (QoL) questionnaire EQ-5D-3L, the Brief Pain Inventory (BPI) and painDETECT. Abbreviated quantitative sensory testing (QST) was also performed, and included mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up pain ratio (WUR) and vibration detection threshold (VDT). Significant pain in patients with PC was confirmed, as indicated by mean BPI severity and interference of 4.2 ± 1.7 and 4.4 ± 2.2, respectively, as well as QoL impairment, as indicated by mean EQ-5D index of 0.69 ± 0.18. PD identified neuropathic pain in 62% of patients, the remainder being nociceptive. The painDETECT score was most significantly related to EQ-5D index (R(2) = 0.26, P = 0.02). The K17 and K6a subtypes exhibited significantly worse QoL (0.584 and 0.613 respectively) than the K16 and K6b subtypes (P = 0.02). In QST analysis, abnormal pressure pain (assessed as MPT) was frequently observed, with more than half of patients with PC affected (54%), and 57% of patients with K17 also exhibiting abnormality in minimum touch threshold (assessed as MDT, P < 0.05). Very few patients were receiving analgesic therapy appropriate for neuropathic pain. Significant neuropathic pain was observed in PC, which warrants appropriate treatment. The health states observed in this sample are at a level that the average US citizen would forfeit one-third of their remaining lifespan to avoid.


Diagnosis and management of soft tissue sarcomas.
STS are a heterogeneous group of malignant tumors that pose significant management challenges. The cornerstone of therapy for patients who have primary STS remains margin-negative resection. Adjuvant radiotherapy has been shown to reduce the risk of recurrence for extremity and trunk STS, although its role for retroperitoneal STS remains to be defined. Neoadjuvant radiotherapy has some theoretic advantages to postoperative radiation, but its exact role has yet to be determined. Chemotherapy is usually reserved for chemotherapy-sensitive histologic subtypes and for patients who have metastatic STS.


Impact of applied progressive deep muscle relaxation training on the level of depression, anxiety and stress among prostate cancer patients: a quasi-experimental study.
The aim of this study was to determine the impact of applied progressive muscle relaxation training on the levels of depression, anxiety and stress among prostate cancer patients. A quasi-experimental study was conducted at the University Malaya Medical Centre (UMMC) and Universiti Kebangsaan Malaysia Medical Centre (UKMMC) over six months. Prostate cancer patients from UMMC received the intervention and patients from UKMMC were taken as controls. The level of depression, anxiety and stress were measured using Depression, Anxiety Stress Scales - 21 (DASS-21). A total of 77 patients from the UMMC and 78 patients from the UKMMC participated. At the end of the study, 90.9% and 87.2% of patients from the UMMC and UKMMC groups completed the study respectively. There were significant improvements in anxiety (p<0.001, partial ?2=0.198) and stress (p<0.001, partial ?2=0.103) at the end of the study in those receiving muscle training. However, there was no improvement in depression (p=0.956). The improvement in anxiety and stress showed the potential of APMRT in the management of prostate cancer patients. Future studies should be carried out over a longer duration to provide stronger evidence for the introduction of relaxation therapy among prostate cancer patients as a coping strategy to improve their anxiety and stress.


Breakthrough instruments and products: DriveAFM for high-performance atomic force microscopy.
Atomic force microscopy is a powerful technique for measurement and mapping of nanoscale topography and electrical and mechanical sample properties. The Nanosurf DriveAFM is a new generation instrument that combines ease of use and high performance through full motorization, CleanDrive photothermal excitation, and a mechanical and electrical design that allows for both high-resolution and large-range imaging.


Purification of human tissue prokallikrein excreted from insect cells by liquid chromatography.
Tissue kallikrein, generally existing in living bodies as prokallikrein, is a serine proteinase that has proven of great significance to treat hypertension, cardiopathy and nephropathy. Although the extraction of tissue kallikrein from human urine is the most commonly used method to obtain such a protein, not only the yield is very little, but also the procedure is rather complex. Furthermore, the biological safety is uncertain. Therefore, the preparation of such a protein by genetic engineering method, including gene expression, cell culture, separation and purification, is very important. In this paper, a new method to obtain purified tissue prokallikrein excreted from insect cells by liquid chromatography has been proposed. In contrast to the previously published papers, the purification procedure is simplified to only three steps with the final yield of 57% and the purity of 95%, which is not only convenient, but also low-cost and suitable for the large-scale preparation of such a protein. The purified protein is further validated as prokallikrein by high performance liquid chromatography-mass spectrometry and amino acid sequencing.


Formation of DNA adducts in mouse skin treated with metabolites of chrysene.
Analysis by 32P-postlabelling of DNA isolated from mouse skin that had been treated in vivo with the polycyclic hydrocarbon chrysene revealed the presence of 7 adducts. All 7 adducts were also present in DNA from mice treated with trans-1,2-dihydro-1,2-dihydroxychrysene (chrysene-1,2-diol), and one of them, adduct 2, was formed from the triol derivative 9-hydroxy-trans-1,2- dihydro-1,2-dihydroxychrysene (9-hydroxychrysene-1,2-diol) and from 3-hydroxychrysene. Adducts were not detected in DNA from mice treated with trans-3,4-dihydro-3,4-dihydroxychrysene (chrysine-3,4-diol) or with 1-, 2-, 4-, 5- or 6-hydroxychrysene. In vitro modification of DNA by the anti-isomer of the bay-region diol-epoxide yielded adducts 3-7, while the corresponding triol-epoxide yielded adducts 2. It is concluded that chrysene activation in mouse skin proceeds principally via the bay-region diol-epoxide and to a lesser extent via the related bay-region triol-epoxide.


In vitro performance characteristics of valved holding chamber and spacer devices with a fluticasone metered-dose inhaler.
To compare the in vitro aerosol deposition characteristics of several commercially available valved holding chamber (VHC) and spacer devices used with a fluticasone metered-dose inhaler (MDI). In vitro aerosol deposition study University-affiliated research center. Seven VHC devices: BreatheRite, E-Z Spacer, EasiVent, AeroChamber, InspirEase, OptiChamber, and Space Chamber. Six spacer devices: OptiHaler, Aerosol Cloud Enhancer (ACE), Gentle-Haler, MediSpacer, Ellipse, and a 6-inch tube (1-inch inside diameter). The respirable dose (aerosol particles 1-5 microm) of fluticasone was determined by sampling 10 220-microg actuations from five runs with each spacer or VHC plus MDI combination, by using a well-established in vitro cascade impactor method. Fluticasone aerosol was washed from the impactor with methanol and quantified by means of high-performance liquid chromatography. Differences among outcomes were determined with analysis-of-variance testing. Among spacers, Ellipse had the highest respirable dose (104 microg, p < 0.01). Respirable doses for the 6-inch tube (74.3 microg), Gentle-Haler (81.7 microg), and MediSpacer (82.6 microg) were no different from that of the MDI (p > 0.05), whereas respirable doses of OptiHaler (44.6 microg) and ACE (47.2 microg) were less than those of all other spacers (p < 0.001). Among VHC devices, respirable doses from EasiVent (35.6 microg), AeroChamber (47.0 microg), InspirEase (52.7 microg), OptiChamber (53.1 microg), and Space Chamber (58.3 microg) were not different (p > 0.05), whereas BreatheRite (13.1 microg) and E-Z Spacer (27.3 microg) respirable doses were less than those of the other VHC devices (p < 0.05). Spacers and VHC devices available in the United States do not demonstrate equivalent in vitro performance with the fluticasone MDI. The difference between highest and lowest respirable doses in each device category would likely lead to clinically relevant differences in the quantity of fluticasone delivered to a patient.


DNA loop domains in a 1.4-Mb region around the human hprt gene mapped by cleavage mediated by nuclear matrix-associated topoisomerase II.
We have mapped the positions in a approximately 1.4-Mb region of genomic DNA around the human hprt gene which are accessible in vivo to cleavage by topoisomerase II associated with the nuclear matrix. These positions, which are interpreted as the boundaries of DNA loop domains, were mapped in K562 cells by examining the truncation of rare-cutter restriction fragments separated by pulsed field gel electrophoresis after topoisomerase II-mediated cleavage, using seven linked markers mapped in this region as probes for indirect end-labeling. Eleven cleavage positions were detected and were interpreted as defining ten loop domains of lengths between 70 and 210 kb (average approximately 135 kb); the hprt gene resides in a 150-kb loop domain. Loop domain boundaries coincided with three of the fifteen deletion breakpoints mapped in a 600-kb sector of this region in human lymphocytes, within the limits of resolution of pulsed field gel electrophoresis; this correlation was not statistically significant.


The distribution of cells of the monocytic-lineage in reactive lymph nodes and non-Hodgkin's lymphomata. Characterization using protein histochemistry, lectin binding and monoclonal antibodies.
In this study cells of putative monocytic origin have been investigated in lymph nodes, using a battery of cytochemical investigations on fixed and frozen tissue. In reactive lymph nodes involved in non-Hodgkin's lymphomata six types of presumed monocyte-derived cells have been identified on the basis of morphology and/or cytochemistry. These cells can be divided into two distinct groups. Certain cell types have distinctive distributions in reactive and non-Hodgkin's lymphomata and this taken in conjunction with their morphology and staining properties may give important clues to their function.


Pulmonary artery plication: a new surgical procedure for small infants with type I truncus arteriosus.
A new technique is reported for constriction of the pulmonary artery ostium as a palliative procedure in infants with type I truncus arteriosus. Pulmonary artery plication was performed without cardiopulmonary bypass, and this allowed intraoperative evaluation of the procedure. The lungs were protected from developing pulmonary vascular obstructive disease, and congestive heart failure resolved. The pulmonary arteries and the ostium grew with the child so that corrective surgery could be delayed until 4 1/2 years of age, when a large (20 mm) valved extracardiac conduit could be placed. We believe this is a useful palliative operation, particularly for small, sick infants, and it deserves further evaluation.


Physicochemical properties and cytotoxicity of cysteine-functionalized silver nanoparticles.
The preparation of stable cysteine-capped silver nanoparticles (AgNPs), via the reduction of silver ions with sodium borohydride and modification of formed nanoparticles by l-cysteine, was developed. The micrographs from transmission electron microscopy (TEM) revealed that the spherical AgNPs exhibited an average size equal to 22±4nm. Surface enhanced Raman spectroscopy (SERS) and inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed a chemisorption of cysteine molecules on the AgNPs. Additionally, dynamic light scattering (DLS) measurements showed that the AgNPs were stable for ionic strength lower than 5×10-3molL-1 and at 6.8<pH<4.5. The electrophoretic mobility measurements allowed to determine the isoelectric point of AgNPs, which appeared at pH 5.1. Below this value, the AgNPs were positively charged with the zeta potential equal to +68±3mV at pH 3.5. Under alkaline condition, the zeta potential of AgNPs was negative, attaining a value of -71±3mV at pH 9.5. The AgNPs were prone to the processes of oxidative dissolution, which was assessed using atomic absorption spectrometry (AAS). The cytotoxicity of AgNPs towards histiocytic lymphoma (U-937) and human promyelocytic (HL-60) cells was studied by the evaluation of changes in mitochondrial functions and cell membrane integrity. In the case of the HL-60 cells, apoptosis caused by the membrane damage was dominant. Furthermore, the obtained results showed the does-dependent impact of the AgNPs on the cell viability. Finally, it was found that the AgNP concentration of 15mgL-1 caused a complete destruction of cells of both types.


Recurrent subependymoma treated with radiosurgery.
Subependymomas are rare, slow-growing intracranial neoplasms of the subependymal matrix. We document a successful case of radiosurgical treatment of a multiply recurrent subependymoma. A nineteen-year-old male developed a recurrent fourth ventricular subependymoma after 6 resections, fractionated radiation therapy (50.4 Gy) and chemotherapy. In addition, a lesion consistent with a cavernous malformation (CM) was noted adjacent to the tumor within the previously irradiated region. Stereotactic radiosurgery was performed covering both the subependymoma and the presumed CM. Fifty-four months after radiosurgery, both lesions had decreased in size and the patient remained neurologically unchanged. Subependymoma may be added to the list of primary glial neoplasms that have been successfully managed with stereotactic radiosurgery. Also, we add a case of presumed CM following radiation therapy to the literature.


A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates.
Methotrexate (MTX)-resistant human breast cancer cells (MTXR ZR-75) were obtained following serial passage of the wild-type ZR-75-1 cells (wild-type ZR-75) in MTX. The resistant cell line contains neither quantitative nor qualitative changes in dihydrofolate reductase compared to the parental line. Resistance is associated with a 3-fold decrease in MTX transport into MTXR ZR-75 cells as well as a 3-fold decrease in the activity of thymidylate synthetase in the resistant subline. Moreover, marked differences were observed between the wild-type and MTXR ZR-75 cells in their ability to convert MTX to its polyglutamate derivatives. Wild-type ZR-75 cells accumulate significant intracellular levels of antifolates during prolonged (24 h) exposure to 2 microM MTX, due to the formation of MTX polyglutamates. In contrast, essentially no polyglutamates are formed in the MTXR cells even during conditions which result in a vast excess of free intracellular drug in these cells. This defect is not associated with any apparent change in the activity of the enzyme folylpolyglutamyl synthetase, nor is there any alteration in the apparent Km of this enzyme for MTX in the resistant cells. Further studies demonstrate that the MTXR ZR-75 cells are cross-resistant to antifolate analogues which can be converted to polyglutamate derivatives (aminopterin and dichloromethotrexate), yet they are relatively sensitive to antifolate analogues such as 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine, triazinate, and trimetrexate, which cannot be converted to polyglutamate forms. These studies identify a new mechanism (diminished accumulation of MTX polyglutamates) associated with resistance to MTX and lend additional support to the hypothesis that the formation of these derivatives is an important determinant of MTX cytotoxicity.


Predictors of Reexcision following Breast-Conserving Surgery for Ductal Carcinoma In Situ.
Reexcision following breast-conserving surgery (BCS) in women with ductal carcinoma in situ (DCIS) results in adjuvant treatment delays, higher health care costs, and undesirable cosmetic outcomes. The purpose of this study is to determine patient, imaging, pathological, and surgical predictors of reexcision following BCS for DCIS. A retrospective review of women with DCIS who had BCS from 2007 to 2016 was conducted. Patient, imaging, pathological, and surgical features, in addition to surgical outcomes, were collected from medical records. Standard statistical tests were used to compare features between patients who did and did not undergo at least one reexcision. A multivariable logistic regression model was fit to assess features associated with reexcision. A total of 547 women (mean age 59 years; range 30-88 years) diagnosed with DCIS at core needle biopsy underwent BCS. Of all women, 31.6% (173/547) had at least one reexcision. With multivariable analysis, features associated with reexcision included younger patient age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.97-1.0, p = 0.049), African-American race (aOR 2.66, 95% CI 1.13-6.26, p = 0.03), biopsy modality of ultrasound (aOR 2.35, 95% CI 1.22-4.53, p = 0.01), and earlier year of surgery (aOR 0.92, 95% CI 0.86-0.98, p = 0.01). No pathological features of DCIS were associated with reexcision risk. In our cohort of nearly 550 women with DCIS who underwent BCS, 31.6% had at least one reexcision. Features associated with reexcision include younger patient age, African-American race, biopsy modality of ultrasound, and earlier year of surgery.


Gender, social engagement, and limitations in late life.
This study examines gender differences in the pathways among social engagement, physical limitations and cognitive limitations among U.S. older adults. It improves upon previous literature by longitudinally testing both social benefit and selection hypotheses, examining gender differences in these relationships, gaining modeling advantages through structural equation modeling, and by incorporating the frequency of participation in social activities as an important source of social integration that may influence health among older adults. This study uses U.S. panel data of adults aged 60 and older from the Americans' Changing Lives survey (N = 1642) from 1986, 1989, and 1994 in a cross-lagged panel design to better understand these relationships. For women, the flow is from greater social engagement to lower levels of subsequent physical and cognitive limitations, whereas for men the flow is from greater physical and cognitive limitations to lower levels of subsequent social engagement.


Differences in peak knee valgus angles between individuals with high and low Q-angles during a single limb squat.
Differences in anatomical alignment between genders have been suggested as causes of the disparity in anterior cruciate ligament injury rates. A larger Q-angle may be associated with increased knee valgus during movement resulting in anterior cruciate ligament strain. This study investigated whether healthy college-aged subjects with a large Q-angle display greater peak knee valgus during a single limb squat compared to those with a small Q-angle. The study also determined whether the high and low Q-angle groups displayed differences in other select anatomical variables, and whether these anatomical variables were related to knee valgus. Twenty subjects, categorized as having a "high Q-angle" (> or = 17 degrees) or a "low Q-angle" (< or = 8 degrees) were videotaped during the performance of a single leg squat. The peak valgus angles for the right knee were calculated. One-tailed independent measures t-tests were used to determine whether individuals with a large Q-angle exhibit (1) significantly greater peak knee valgus during a single leg squat compared to those with a small Q-angle and, (2) greater pelvic width to femoral length ratios and greater static knee valgus than subjects with a small Q-angle. The Pearson product-moment correlation was used to establish the relationships between pelvic width to femoral length ratios and static knee valgus, pelvic width to femoral length ratios and dynamic knee valgus, and static knee valgus and dynamic knee valgus. Peak knee valgus during the single leg squat, and static knee valgus were not significant greater in the high Q-angle group compared to the low Q-angle group (P=0.09; P=0.31). Subjects with a larger Q-angle, however, had a significantly greater pelvic width to femoral length ratios (P=0.015) compared to subjects with a small Q-angle. Pelvic width to femoral length ratios was related to both static and dynamic knee valgus (r=0.47, P=0.02; r=0.48, P=0.02), but static knee valgus was not related to dynamic knee valgus. The findings suggest that pelvic width to femoral length ratios, rather than Q-angle, may be a better structural predictor of knee valgus during dynamic movement.


Early motor repertoire and developmental function outcomes in infants with West syndrome: a case series.
West syndrome (WS), also known as infantile spasm, is a rare form of severe epilepsy that begins during early infancy. This case series aimed to describe the early motor repertoire and examine the developmental function outcomes of infants with WS. Three infants (one female) with WS were assessed for early motor repertoire using the General Movement Assessment (GMA) which determined General Movement Optimality Scores (GMOS) at 4 post-term weeks of age, and Motor Optimality Scores (MOS) at 12 post-term weeks of age. Cognitive, language, and motor development were evaluated with the Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) at 3, 6, 12, and 24 months of age. At 4-weeks post-term, one infant showed poor repertoire movements, while the other two showed cramped-synchronized movements with their GMOS ranging from 6 to 16 (out of 42). All infants showed sporadic/absent fidgety movements at 12 weeks post-term with their MOS ranging from 5 to 9 (out of 28). All sub-domain scores of Bayley-III were <2 SD at all follow-up assessments, that is <70, indicating severe developmental delay. These infants with WS had less than optimal scores of early motor repertoire, and developmental delay at a later age. Early motor repertoire might be an early sign for developmental function outcome at a later age in this population suggesting the need for additional research.


Cardiovascular responses produced by the injection of dopamine into the cerebral ventricles of the unanaesthetized dog.
1 The injection of dopamine (100 to 500 microgram) into the cerebral ventricles (i.c.v.) of 10 unanaesthetized dogs produced a dose-dependent increase in arterial blood pressure and heart rate. The dogs licked, swallowed, sometimes vomited and became sedated. 2 Autonomic ganglion blockade with hexamethonium (10 mg/kg i.v.) abolished cardiovascular responses to i.c.v. dopamine, indicating that dopamine was exerting its effect within the central nervous system. 3 The dopamine receptor antagonists, haloperidol (500 microgram), chlorpromazine (200 micrograms) and ergometrine (500 micrograms), each given i.c.v., sugsequently abolished the cardiovascular responses to dopamine. 4 Pretreatment with either the beta-adrenoceptor antagonist, propranolol (600 microgram) or the alpha-adrenoceptor antagonist, phentolamine (1 mg) given i.c.v. had no significant effect on the response to dopamine. 5 It is suggested that dopamine injected into the cerebral ventricles of the unanesthetized dog causes hypertension and tachycardia by activating central dopamine receptors.


What is the potential of paramagnetic rim lesions as diagnostic indicators in multiple sclerosis?
In multiple sclerosis (MS), paramagnetic rim lesions (PRLs) on MRI identify a subset of chronic active lesions (CALs), which have been linked through clinical and pathological studies to more severe disease course and greater disability accumulation. Beside their prognostic relevance, increasing evidence supports the use of PRL as a diagnostic biomarker. This review summarizes the most recent updates regarding the MRI pathophysiology of PRL, their prevalence in MS (by clinical phenotypes) vs mimicking conditions, and their potential role as diagnostic MS biomarkers. We searched PubMed with terms including 'multiple sclerosis' AND 'paramagnetic rim lesions' OR 'iron rim lesions' OR 'rim lesions' for manuscripts published between January 2008 and July 2022. Current research suggests that PRL can improve the diagnostic specificity and the overall accuracy of MS diagnosis when used together with the dissemination in space MRI criteria and the central vein sign. Nevertheless, future prospective multicenter studies should further define the real-world prevalence and specificity of PRL. International guidelines are needed to establish methodological criteria for PRL identification before its implementation into clinical practice.


Descriptions of two new species of Lestica Billberg (Hymenoptera, Apoidea, Crabronidae) from China, with a key to the Chinese Lestica species.
Two new species of the genus Lestica Billberg (Crabronidae: Crabroninae: Crabronini) from China are described and illustrated, namely L. robustispinosa Yue Ma from Xinjiang, and L. breviantennata Yue Li from Jiangxi, Hunan and Yunnan Provinces. A key to the species of Lestica from China is provided.


Systematic review and meta-analysis of the pre-operative application of botulinum toxin for ventral hernia repair.
Surgical repair of large hernia defects requires detailed pre-operative planning, particularly in cases with loss of domain. This situation often hampers mid-line reconstruction, even after component separation, when the size of the hernia is disproportional to the volume of the abdominal area. In this case, other strategies may be needed to place the viscera back into the abdominal cavity after reducing the hernia sac. The administration of botulinum toxin prior to the surgical procedure has been indicated as an adjunct for more complex cases. This results in stretching of the lateral musculature of the abdomen, allowing midline approximation. In addition, the application of botulinum toxin alone has been investigated as a means of downstaging in the management of ventral hernias, thereby precluding component separation and enabling primary closure of the midline by placement of mesh within the retromuscular space using the Rives Stoppa technique. Systematic review of the literature for observational studies involving patients undergoing pre-operative application of botulinum toxin for ventral hernia repair was conducted according to the PRISMA guidelines. Advance of the lateral musculature of the abdomen by an average of 4.11 cm with low heterogeneity, as well as low rates of surgical site infection (SSI), surgical site occurrences (SSO) and recurrence, was shown. Pre-operative application of botulinum toxin for ventral hernia repair promoted an increase in the length of the lateral musculature of the abdomen which can help improve the outcomes of morbidity and recurrence.


Efficacy of COVID-19 vaccines: a systematic review and network meta-analysis of phase 3 randomized controlled trials.
Several vaccines have been approved for the prevention of COVID-19. However, no head-to-head trials comparing their clinical efficacy have been performed. This network meta-analysis aims to identify those, among the competing existing vaccines, conferring the maximum protection against COVID-19. A literature search was done in Medline (via PubMed), Embase and Cochrane Library databases for phase 3 randomized controlled trials evaluating the efficacy of different COVID-19 vaccines. Search results were screened and eligible studies were included to perform a network meta-analysis in software 'R' version 4.1.2 using a random effect model. Cochrane's 'Risk of Bias tool (RoB2)' was used for quality assessment. Raw data from the included studies was used for network meta-analysis. Assessment of inconsistency was not possible as no study compared two or more vaccines directly. A forest plot for indirect comparison of various COVID-19 vaccines was obtained. Rankogram and 'P' scores were obtained to rank the vaccines based on the indirect evidence of their comparative efficacy. A total of 17 randomized controlled trials evaluating the efficacy of 16 COVID-19 vaccines, were included in the network meta-analysis. A total of 361,386 participants was included in this network meta-analysis. Overall risk of bias among included studies was of 'some concern'. All the COVID-19 vaccines had a statistically significant reduction of risk for contracting symptomatic SARS-CoV-2 in comparison to the placebo, however, the maximum protection (RR 0.05) was with BNT126b2. The indirect comparison also revealed BNT126b2 vaccine confers the highest protection against symptomatic SARS-CoV-2 infection in comparison to all others included, with a 'P' score of 0.9771 followed by mRNA-1273, rAD26 & rAD5 and NVX-CoV2373. The evidence generated from this network meta-analysis indicates the good efficacy of all the included vaccines in preventing symptomatic COVID-19 as compared to placebo. The BNT126b2 vaccine was found to provide the highest protection against symptomatic SARS-CoV-2 among all included followed by mRNA-1273, rAD26 & rAD5, NVX-CoV2373 and others.


Model curriculum for physician training in emergency ultrasonography.
A model curriculum for the implementation and training of physicians in emergency medicine ultrasonography is described. Widespread use of limited bedside ultrasonography by emergency physicians will improve diagnostic accuracy and efficiency, increase the quality of care, and prove to be a cost-effective technique for the practice of emergency medicine.


Combination of BMP2 and EZH2 Inhibition to Stimulate Osteogenesis in a 3D Bone Reconstruction Model.
High concentrations of bone morphogenetic protein 2 (BMP2) in bone regeneration cause adverse events (e.g, heterotopic bone formation and acute inflammation). This study examines novel epigenetic strategies (i.e., EZH2 inhibition) for augmenting osteogenesis, thereby aiming to reduce the required BMP2 dose in vivo for bone regeneration and minimize these adverse effects. Human bone marrow-derived mesenchymal stem cells (BMSCs) were grown on three-dimensional (3D)-printed medical-grade polycaprolactone scaffolds and incubated in osteogenic media containing 50 ng/mL BMP2 and/or 5 μM GSK126 (EZH2 inhibitor) for 6 days (n = 3 per group and timepoint). Constructs were harvested for realtime quantitative polymerase chain reaction analysis at Day 10 and immunofluorescence (IF) microscopy at Day 21. After pretreating for 6 days and maintaining in osteogenic media for 4 days, BMSC-seeded scaffolds were also implanted in an immunocompromised subcutaneous murine model (n = 39; 3/group/donor and 3 control scaffolds) for histological analysis at 8 weeks. Pretreatment of BMSCs with BMP2 and BMP2/GSK126 costimulated expression of osteoblast-related genes (e.g., IBSP, SP7, RUNX2, and DLX5), as well as protein accumulation (e.g., collagen type 1/COL1A1 and osteocalcin/BGLAP) based on IF staining. While in vivo implantation for 8 weeks did not result in bone formation, increased angiogenesis was observed in BMP2 and BMP2/GSK126 groups. This study finds that BMP2 and GSK126 costimulate osteogenic differentiation of MSCs on 3D scaffolds in vitro and may contribute to enhanced vascularization when implanted in vivo to support bone formation. Thus, epigenetic priming with EZH2 inhibitors may have translational potential in bone healing by permitting a reduction of BMP2 dosing in vivo to mitigate its side effects. Impact statement While autografts are still the gold standard for bone reconstruction, tissue availability and donor morbidity are significant limitations. Previous attempts to use high concentrations of bone morphogenetic protein 2 (BMP2) have been shown to cause adverse events such as excessive bone formation and acute inflammation. Overall, the utilization of EZH2 inhibitors to modulate gene expression in favor of bone healing has been demonstrated in vitro in a tissue engineering strategy. Our study will pave the way to developing tissue engineering strategies involving GSK126 as an adjuvant to increase the effects of BMP2 for stimulating cells of interest on a three-dimensional scaffold for bone regeneration.


Synthesis and biological activity of selective azasugar-based TACE inhibitors.
A series of azasugar-based hydroxamic acid derivatives bearing 2R,3R,4R,5R-configuration is described. Compound 4c with 4,5-O-acetonide group showed excellent in vitro potency against TACE, with high selectivity over MMP-1 and moderate selectivity over MMP-3 and MMP-9.


Prevalence of HI antibody titer against rubella virus to determine the effect of mass vaccination in Tehran.
Rubella is an infectious viral disease, has a worldwide distribution and is normally a mild childhood disease. Infection during early pregnancy may cause fetal death or congenital rubella syndrome. The highest risk of CRS is found in countries with high susceptibility rates among women of childbearing age. In many developed and some developing countries, large-scale rubella vaccination during the past decade has drastically reduced or practically eliminated rubella and CRS. Mass vaccination campaigns and Expanded Program of Immunization (EPI) have increased vaccine coverage in the world with a substantial impact on the reduction of rubella infections, such as CRS. The present study was preformed to evaluate the immune status against rubella before and after the mass campaign vaccination on 22 December 2003. A total of 320 samples were collected from the healthy subjects before and after the vaccination and 80 paired sera were collected and tested for the presence of rubella antibody using HI test. Based on the results, 98.1% of the population has gained anti-rubella antibody, compared with 92.2% before the vaccination. The data revealed that 98.75% of the paired subjects had rubella antibody after mass vaccination which is statistically significant.


Rapid kinetics of calcium dissociation from plant calmodulin and calmodulin-like proteins and effect of target peptides.
Calcium (Ca2+) signaling represents a universal information code in plants, playing crucial roles spanning developmental processes to stress responses. Ca2+ signals are decoded into defined plant adaptive responses by different Ca2+ sensing proteins, including calmodulin (CaM) and calmodulin-like (CML) proteins. Although major advances have been achieved in describing how these Ca2+ decoding proteins interact and regulate downstream target effectors, the molecular details of these processes remain largely unknown. Herein, the kinetics of Ca2+ dissociation from a conserved CaM and two CML isoforms from A. thaliana has been studied by fluorescence stopped-flow spectroscopy. Kinetic data were obtained for the isolated Ca2+-bound proteins as well as for the proteins complexed with different target peptides. Moreover, the lobe specific interactions between the Ca2+ sensing proteins and their targets were characterized by using a panel of protein mutants deficient in Ca2+ binding at the N-lobe or C-lobe. Results were analyzed and discussed in the context of the Ca2+-decoding and Ca2+-controlled target binding mechanisms in plants.


Comparison of percutaneous transforaminal endoscopic decompression and short-segment fusion in the treatment of elderly degenerative lumbar scoliosis with spinal stenosis.
Degenerative lumbar scoliosis (DLS) combined with spinal stenosis is increasingly being diagnosed in the elderly. However, the appropriate surgical approach remains somewhat controversial. The aim of this study was to compare the results of percutaneous transforaminal endoscopic decompression (PTED) and short-segment fusion for the treatment of mild degenerative lumbar scoliosis combined with spinal stenosis in older adults over 60 years of age. Of the 54 consecutive patients included, 30 were treated with PTED and 24 were treated with short-segment open fusion. All patients were followed up for at least 12 months (12-24 months). Patient demographics, and perioperative and clinical outcomes were recorded. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, and modified Macnab criteria were used to assess clinical outcomes. At the same time, changes in disc height, segmental lordosis, coronal Cobb angle, and lumbar lordosis were compared. The mean age was 68.7 ± 6.5 years in the PTED group and 66.6 ± 5.1 years in the short-segment fusion group. At 1 year postoperatively, both groups showed significant improvement in VAS and ODI scores compared with preoperative scores (p < 0.05), with no statistically significant difference between groups. However, VAS-Back and ODI were lower in the PTED group at 1 week postoperatively (p < 0.05). According to the modified Macnab criteria, the excellent rates were 90.0 and 91.6% in the PTED and short-segment fusion groups, respectively. However, the PTED group had a significantly shorter operative time, blood loss, postoperative hospital stay, postoperative bed rest, and complication rate. There was no significant difference in radiological parameters between the two groups preoperatively. At the last follow-up, there were significant differences in disc height, segmental lordosis at the L4-5 and L5-S1 levels, and Cobb angle between the two groups. Both PTED and short-segment fusion for mild degenerative lumbar scoliosis combined with spinal stenosis have shown good clinical results. PTED under local anesthesia may be an effective supplement to conventional fusion surgery in elderly patients with DLS combined with spinal stenosis.


Water quality index evaluation for major rivers in Gujarat.
Water quality index (WQI) is used for representing the overall water quality in the form of a number to qualify its use for domestic, irrigation, industry or any other intended use. The present study involves determination of WQI using various physicochemical characteristics like pH, electrical conductivity, DO, BOD, nitrate nitrogen and total coliform for surface water samples for rivers Mahi, Sabarmati, Narmada and Tapi in Gujarat for the year 2016. The WQI for river Mahi was found between 30 and 50, for river Sabarmati between 42 and 65, for River Narmada between 28 and 52 and for river Tapi between 35 and 70. Based on WQI, it can be inferred that most of the surface water samples are in the category of good to poor. The quality of river water was good on upstream as compared with downstream. It can be inferred that the chief reason for decline in the quality of river water was discharge of sewage, industrial effluent and urban runoff.


Megaureter visualization on Tc-99m DMSA scintigraphy.
We present a patient with left-sided obstructed megaureter secondary to neuropathic bladder. He was referred for technetium-99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal cortical scintigraphy to evaluate renal cortical function. Images obtained 4 hr after injection showed significant activity in the dilated left ureter. When the ureter is visualized on DMSA scan, obstructive megaureter should be considered in the differential diagnosis.


Prolonged hypervolemic hemodilution decreases functional capillary density of ileal mucosa in pigs revealed by sidestream dark-field imaging.
Hemodilution changes the physical properties of blood by reducing its hematocrit and blood viscosity. We tested whether prolonged hypervolemic hemodilution (HHD) impairs functional capillary density (FCD) of ileal mucosa in healthy mechanically-ventilated pigs and if there is any correlation between changes in FCD of ileal and sublingual mucosas during HHD. Sixteen domestic female pigs were anesthetized, mechanically-ventilated, and randomly assigned to the HHD (20 ml/(kg∙h) Hartmann's solution for 3 h) or fluid restrictive (5 ml/(kg∙h) Hartmann's solution for 3 h) group. Microcirculations of sublingual and ileal mucosas via ileostomy were visualized using sidestream dark-field (SDF) imaging at baseline conditions (t=0 h) and at selected time intervals of fluid therapy (t=1, 2, and 3 h). A significant decrease of ileal FCD (285 (278-292) cm/cm(2)) in the HHD group was observed after the third hour of HHD when compared to the baseline (360 (350-370) cm/cm(2)) (P<0.01). This trend was not observed in the restrictive group, where the ileal mucosa FCD was significantly higher after the third hour of fluid therapy as compared to the HHD group (P<0.01). No correlation between microhemodynamic parameters obtained from sublingual and ileal mucosas was found throughout the study. Prolonged HHD established by crystalloid solution significantly decreased ileal villus FCD when compared to restrictive fluid regimen. An inappropriate degree of HHD can be harmful during uncomplicated abdominal surgery.


Does health insurance solve health care utilization puzzle in Tanzania?
The global target of achieving universal health coverage by 2030 is a nightmare in most developing countries. To seek in-depth reasons, this study examines the effects of health insurance on healthcare utilization in Tanzania. This study used a non-experimental research design. Probit model, negative binomial regression, and instrumental variable Poisson with generalized method of moments were used to solve the healthcare utilization puzzle by the use of Andersen Health Care Utilization Model by using the Tanzania Panel Survey data of 2020/21. The findings showed that education level, income, age, residence, household size, insurance, and distance from homestead to health facilities are significant policy intervention factors for improving households' healthcare utilization behavior among households in Tanzania. Prioritize should be made on interventions that ensure the affordability of health services without compromising the quality of services offered and expanding the share of the government budget on health sector.


Correction: KML001 Induces Apoptosis and Autophagic Cell Death in Prostate Cancer Cells via Oxidative Stress Pathway.
[This corrects the article DOI: 10.1371/journal.pone.0137589.].


Pharmacologic treatment of fibromyalgia.
Fibromyalgia is a syndrome of widespread pain, nonrestorative sleep, disturbed mood, and fatigue. Optimal treatment involves a multidisciplinary approach with a team of health care providers using pharmacologic and nonpharmacologic treatment. Because of the heterogeneity of the illness, management should be individualized for the patient. Pharmacologic treatment should address issues of pain control, sleep disturbance, fatigue, and any underlying coexisting mood disorder. Nonpharmacologic treatment should include patient education, a regular exercise and stretching program, and cognitive behavioral therapy. All of these are essential to improving functional capacity and quality of life. This review provides general guidelines in initiating a successful pharmacologic treatment program for patients with fibromyalgia.


Biomimetic synthesis of iron oxide nanoparticles from Bacillus megaterium to be used in hyperthermia therapy.
The suitable structural characteristics of magnetic nanoparticles have resulted in their widespread use in magnetic hyperthermia therapy. Moreover, they are considered a proper and operational choice for pharmaceutical nanocarriers. Using the biomimetic method, we were able to produce iron oxide magnetic nanoparticles from the bacterial source of PTCC1250, Bacillus megaterium, for therangostic diagnosis systems and targeted drug delivery. Some of the benefits of this method include mitigated environmental and biological dangers, low toxicity, high biocompatibility, cheap and short-term mass production possibilities in each synthesis round compared to other biological sources, simple equipment required for the synthesis; and the possibility of industrial-scale production. Bacillus megaterium is a magnetotactic bacteria (MTB) that has a magnetosome organelle capable of orienting based on external magnetic fields, caused by the mineralization of magnetic nanocrystals. Utilizing this capability and adding an iron nitrate solution to the bacterial suspension, we synthesized iron oxide nanoparticles. The extent of synthesis was measured using UV-visible spectrophotometry. The morphology was evaluated using FESEM. The crystallized structure was characterized using RAMAN and XRD. The size and distribution of the nanoparticles were assessed using DLS. The surface charge of the nanoparticles was measured using zeta potential. The synthesis of iron oxide nanoparticles was confirmed using FT-IR, and the magnetic property was measured using VSM. This study is continued to identify industrial and clinical applications.


Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma.
Cell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus-pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. To evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. Eighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. There was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. Patients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study.


Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells.
A decisive role in cancer development has been attributed to cyclooxygenase-2 (COX-2) activity, but the significance of COX-2 inhibitors in cancer treatment still needs to be thoroughly investigated. We studied the influence of meloxicam, a non-steroidal antiinflammatory drug with preferential inhibitory effects on COX-2 compared to COX-1, on canine osteosarcoma (D-17) cells. We demonstrated that D-17 cells expressed mRNA and COX-2 protein. Treatment with meloxicam induced a time- and dose-dependent inhibition of cellular growth. To determine if apoptosis plays a role in meloxicam-induced cell death, we performed agarose gel electrophoresis and found a DNA-ladder pattern, typically seen in apoptosis, as well as early apoptotic changes by Annexin V tests. Furthermore, electron microscopy revealed ultrastructural alterations typical of apoptosis. Quantification of apoptotic cells by immunohistochemical staining of caspase 3 confirmed the results. However, further studies with meloxicam are necessary to assess its potential use for treatment of osteosarcomas in dogs.


High prevalence of erythromycin resistance and macrolide-resistance genes, mefA and ermB, in Streptococcus pneumoniae isolates from the upper respiratory tracts of children in the Sapporo district, Japan.
Our previous study demonstrated that the frequency of penicillin-resistant Streptococcus pneumoniae (PRSP) was lower in our district than in districts in other Japanese studies. In this study, we investigated the prevalence of erythromycin resistance. The susceptibility to erythromycin and the distribution of the macrolide-resistance genes, mefA and ermB, were examined in S. pneumoniae isolates from the upper respiratory tracts of children in four cities in the Sapporo district, Hokkaido prefecture, Japan. Of the 156 isolates, 27 (17.3%) were erythromycin-sensitive, 6 (3.9%) were erythromycin-intermediately resistant, and 123 (78.9%) were erythromycin-resistant. Fifty-nine (37.8%) had the mefA gene, 89 (57.1%) had the ermB gene, and 129 (82.7%) had the mefA and/or the ermB gene. The ermB-positive isolates tended to show high resistance to erythromycin. Erythromycin-resistant isolates and the macrolide-resistance genes were often present in infants or younger children. The frequency of erythromycin-resistant isolates in the four cities was very high, ranging from 76.3% to 83. 3%, as high as the national average. Although erythromycin-resistant isolates generally tend to show cross-resistance to penicillin, the frequency of PRSP was very low in this study, as compared with other Japanese studies. Erythromycin resistance was frequently recognized not only in PRSP but also in penicillin-sensitive S. pneumoniae (PSSP) as well. In Japan, erythromycin resistance may have already become widespread, even in local areas where penicillin resistance is not especially prevalent.


Long-Wavelength Lead Sulfide Quantum Dots Sensing up to 2600 nm for Short-Wavelength Infrared Photodetectors.
Lead sulfide nanoparticles (PbS NPs) are used in the short-wavelength infrared photodetectors because of their excellent photosensitivity, band gap tunability, and solution processability. It has been a challenge to synthesize high-quality PbS NPs with an absorption peak beyond 2000 nm. In this work, using PbS seed crystals with an absorption peak at 1960 nm, we report a successful synthesis of very large monodispersed PbS NPs having a diameter up to 16 nm by multiple injections. The resulting NPs have an absorption peak over 2500 nm with a small full width at half-maximum of 24 meV. To demonstrate the applications of such large quantum dots (QDs), broadband heterojunction photodetectors are fabricated with the large PbS QDs of an absorption peak at 2100 nm. The resulting devices have an external quantum efficiency (EQE) of 25% (over 50% internal quantum efficiency) at 2100 nm corresponding to a responsivity of 0.385 A/W and an EQE of ∼60% in the visible range.


Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids.
The re-emergence of Zika virus (ZIKV) in the Western Hemisphere has resulted in global public health crisis since 2015. ZIKV preferentially infects and targets human neural progenitor cells (hNPCs) and causes fetal microcephaly upon maternal infection. hNPCs not only play critical roles during fetal brain development, but also persist in adult brain throughout life. Yet the mechanism of innate antiviral immunity in hNPCs remains largely unknown. Here, we show that ZIKV infection triggers the abundant production of virus-derived small interfering RNAs in hNPCs, but not in the more differentiated progenies or somatic cells. Ablation of key RNAi machinery components significantly enhances ZIKV replication in hNPCs. Furthermore, enoxacin, a broad-spectrum antibiotic that is known as an RNAi enhancer, exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells. Strikingly, enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid models that recapitulate human fetal brain development. Our findings highlight the physiological importance of RNAi-mediated antiviral immunity during the early stage of human brain development, uncovering a novel strategy to combat human congenital viral infections through enhancing RNAi.


Tumor necrosis factor alpha (TNF alpha) and neurological diseases. Failure in detecting TNF alpha in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours.
The presence of tumor necrosis factor alpha (TNF alpha)/cachectin was investigated in 180 paired cerebrospinal fluid (CSF) and serum samples from patients with neurological diseases, and in five paired CSF and serum samples of Macaca cynomolgus monkeys with acute monophasic experimental autoimmune encephalomyelitis (AMEAE). TNF alpha was never detected in human CSF, even when an extensive demyelination was documented (active multiple sclerosis, acquired immunodeficiency syndrome (AIDS) dementia complex). Only one Macaca with AMEAE had detectable levels of TNF alpha in CSF but not in serum, suggesting an intrathecal synthesis of this cytokine in AMEAE.


Helicobacter pylori status in family members as risk factors for infection in children.
This study aimed to disentangle the independent contributions of Helicobacter pylori infections in mothers, fathers and siblings to the risk for the infection in the 11-13 years age group. Index children from a cross-sectional Stockholm school survey and their family members completed questionnaires and contributed blood samples. H. pylori serostatus was determined with an enzyme-linked immunosorbent assay and immunoblot. Fifty-four seropositive and 108 seronegative index children were included and 480 out of 548 family members contributed blood. In multivariate logistic regression modelling, having an infected mother (OR 11.6, 95% CI 2.0-67.9) or at least one infected sibling (OR 8.1, 95% CI 1.8-37.3) were risk factors for index child infection, whilst the influence of infected fathers was non-significant. Birth in high-prevalence countries was an independent risk factor (OR 10.4, 95% CI 3.4-31.3). H. pylori infections in mothers and siblings and birth in high-prevalence countries stand out as strong markers of infection risk amongst children in Sweden.


Study on the calculation method and structural dynamic response of buried pipeline subjected to external explosion load based on multiphase coupling.
When the buried pipeline is subjected to the external explosion load, stress and deformation will occur. When the stress and deformation value exceed a specific range, it will affect the normal use of the buried pipeline. In this paper, a multiphase coupled model of pipeline, soil and fluid within the pipeline is established. The penalty function coupling method is used to describe the load between soil and pipeline and the fluid within the pipeline. By specifying the boundary conditions of the coupled system, the multiphase coupled global solution variational principle function of the soil-pipe-fluid is derived. According to the established multiphase coupled calculation method, the numerical simulation analysis of the response of pipeline to external explosion is carried out. The maximum error of the experimental and numerical simulation results is about 5%, which verifies the accuracy of the multiphase coupled calculation method. The soil-pipeline-fluid multiphase coupled numerical calculation model is established to analyze the response of the buried pipeline under the external explosion load. The results show that during the explosion shock wave propagating in the soil, the peak value of the explosion pressure in different positions in the soil of the gas pipeline is greater than that of the oil pipeline. As for the structural response, the maximum radial displacement value of the oil pipeline is reduced by 3.83 mm compared with the gas pipeline, the maximum stress value is reduced by 3.75%. The maximum radial displacement value of the pipeline with a fluid velocity of 1.5 m/s is 2.65 mm larger than that of the pipeline with a fluid velocity of 1 m/s, and the maximum stress value is increased by 5.72%. The deformation resistance and explosion resistance of the oil pipeline are both stronger than that of the gas pipeline. The higher the fluid velocity, the weaker the pipeline's resistance to deformation and explosion will be.


Cissus quadrangularis prevented the ovariectomy induced oxidative stress in the femur of adult albino rats.
The increasing evidence suggesting the role of free radicals in bone resorption and bone loss prompted us to explore whether the consumption of antioxidant rich medicinal plant C. quadrangularis modifies antioxidant status in ovariectomized rats. Twenty four female adult rats, 90days old showing regular estrous cycles were used for the present study. The animals were divided into two groups. The Group-1 rats (n=6) were sham operated and Group-II rats were bilaterally ovariectomized (n=18) and treated with C. quadrangularis for sixty days (100mg/kg body weight and 250mg/kg body weight). After sixty days, the rats were killed, femora were dissected out, minced and homogenized in Tris-HCl buffer (pH 7.4) and the supernatant was collected and used for biochemical assays. Ovariectomy registered a decrease (p<0.05) in the activities of SOD, GPx, GST, ALP, collagen content and increased (p<0.05) the activities of TRAP and lipid peroxidation. Simultaneous administration of C. quadrangularis maintained the enzyme activities in ovariectomized rats. C. quadrangularis, a natural herb may be used to treat the estrogen deficiency/menopause onset and ovariectomy induced oxidative stress.


[Effect of the conditions of incubating bone marrow from totally irradiated mice on the expression of its stem cell potentials].
Incubation, in various conditions, of bone-marrow samples taken from irradiated (7 Gy) (CBA X C57Bl)F1 mice and the subsequent testing thereof for stem potency in the exposed (8.5 Gy) recipients have demonstrated, with certain admissions, that stem cells can recover from radiation injury in certain experimental conditions.


Exploring the potential of chitosan-based particles as delivery-carriers for promising antimicrobial glycolipid biosurfactants.
Driven by the need to find alternatives to control Staphylococcus aureus infections, this work describes the development of chitosan-based particulate systems as carriers for antimicrobial glycolipids. By using a simple ionic gelation method stable nanoparticles were obtained showing an encapsulation efficiency of 41.1 ± 8.8 % and 74.2 ± 1.3 % and an average size of 210.0 ± 15.7 nm and 329.6 ± 8.0 nm for sophorolipids and rhamnolipids chitosan-nanoparticles, respectively. Glycolipids incorporation and particle size was correspondingly corroborated by FTIR-ATR and TEM analysis. Rhamnolipids chitosan nanoparticles (RLs-CSp) presented the highest antimicrobial effect towards S. aureus (ATCC 25923) exhibiting a minimal inhibitory concentration of 130 μg/mL and a biofilm inhibition ability of 99 %. Additionally, RLs-CSp did not interfere with human dermal fibroblasts (AG22719) viability and proliferation under the tested conditions. The results revealed that the RLs-CSp were able to inhibit bacterial growth showing adequate cytocompatibility and might become, after additional studies, a valuable approach to prevent S. aureus related infections.


Atherosclerotic Cardiovascular Disease in Type 2 Diabetes: A Retrospective, Observational Study of Economic and Clinical Burden in Sweden.
Individuals with type 2 diabetes (T2D) are at high risk of experiencing atherosclerotic cardiovascular disease (ASCVD), which is associated with morbidity, mortality and healthcare resource utilisation. Clinical guidelines recommend the use of glucose-lowering medications with cardiovascular benefits in individuals with T2D and cardiovascular disease, but there is evidence that this is not reflected in clinical practice. We used linked national registry data from Sweden to compare outcomes in people with T2D and ASCVD against matched controls with T2D without ASCVD, over 5 years. Direct costs (inpatient, outpatient and selected drug costs), indirect costs resulting from work absence, early retirement, cardiovascular events and mortality were examined. Individuals with T2D who were at least 16 years old and were alive and resident in Sweden on 1 January 2012 were identified in an existing database. In four separate analyses, individuals with a record indicating ASCVD according to a broad definition, peripheral artery disease (PAD), stroke or myocardial infarction (MI) before 1 January 2012 were identified using diagnosis and/or procedure codes and propensity score matched 1:1 to controls with T2D and without ASCVD, using covariates for birth, sex and level of education in 2012. Follow-up continued until death, migration from Sweden or the end of the study period in 2016. In total, 80,305 individuals with ASCVD, 15,397 individuals with PAD, 17,539 individuals with previous stroke and 25,729 individuals with previous MI were included. Total mean annual costs per person were €14,785 for PAD (2.7 × costs for controls), €11,397 for previous stroke (2.2 × controls), €10,730 for ASCVD (1.9 × controls) and €10,342 for previous MI (1.7 × controls). Indirect costs and costs of inpatient care were the major cost drivers. ASCVD, PAD, stroke and MI were all associated with an increased likelihood of early retirement, cardiovascular events and mortality. ASCVD is associated with considerable costs, morbidity and mortality in individuals with T2D. These results support structured assessment of ASCVD risk and broader implementation of guideline-recommended treatments in T2D healthcare.


Fraction-variant beam orientation optimization for intensity-modulated proton therapy.
To achieve a superior balance between dosimetry and the delivery efficiency of intensity-modulated proton therapy (IMPT) using as few beams as possible in a single fraction, we optimally vary beams in different fractions. In the optimization, 400~800 feasible noncoplanar beams were included in the candidate pool. For each beam, the doses of all scanning spots covering the target volume and a margin were calculated. The fraction-variant beam orientation optimization (FVBOO) problem was formulated to include three terms: two quadratic dose fidelity terms to penalize the deviation of planning target volume fractional dose and organs at risk (OAR) cumulative doses from prescription, respectively; an L2,1/2-norm group sparsity term to control the number of active beams per fraction to between 1 and 4. The Fast Iterative Shrinkage-Thresholding Algorithm (FISTA) was applied to solve this problem. FVBOO was tested on a patient with base-of-skull (BOS) tumor of 5 fractions (5f) and 30 fractions (30f) with an average number of active beams per fraction varying between 4 and 1. In addition, one bilateral head-and-neck (H&N) patient, and one esophageal cancer (ESG) patient of 30f were tested with about three active beams per fraction. The results were compared with IMPT plans that use fixed beams in each fraction. The fixed beams were selected using the group sparsity term with a fraction-invariant BOO (FIBOO) constraint. Varying beams were chosen in either the 5f or 30f FVBOO plans. While similar number of beams per fraction was selected as the FIBOO plan, the FVBOO plans were able to spare the OARs better, with an average reduction of [Dmean, Dmax] from the FIBOO plans by [0.85, 2.08] Relative Biological Effective Gy (GyRBE) in the 5f plan and [1.87, 4.06] GyRBE in the 30f plans. While reducing the number of beams per fraction in the BOS patient, a three-beam/fraction 5f FVBOO plan performs comparably as the four-beam FIBOO plan and a two-beam/fraction 30f FVBOO plan still provides superior dosimetry. Fraction-variant beam orientation optimization allows the utilization of a larger beam solution space for superior dose distribution in IMPT while maintaining a practical number of beams in each fraction.


How safe is the treatment of pregnant women with fear of childbirth using eye movement desensitization and reprocessing therapy? Obstetric outcomes of a multi-center randomized controlled trial.
Pregnant women with fear of childbirth display an elevated risk of a negative delivery experience, birth-related post-traumatic stress disorder, and adverse perinatal outcomes such as preterm birth, low birthweight, and postpartum depression. One of the therapies used to treat fear of childbirth is eye movement desensitization and reprocessing (EMDR) therapy. The purpose of the present study was to determine the obstetric safety and effectiveness of EMDR therapy applied to pregnant women with fear of childbirth. A randomized controlled trial (the OptiMUM-study) was conducted in two teaching hospitals and five community midwifery practices in the Netherlands (www.trialregister.nl, NTR5122). Pregnant women (n = 141) with a gestational age between 8 and 20 weeks and suffering from fear of childbirth (i.e. sum score on the Wijma Delivery Expectations Questionnaire ≥85) were randomly allocated to either EMDR therapy (n = 70) or care-as-usual (CAU) (n = 71). Outcomes were maternal and neonatal outcomes and patient satisfaction with pregnancy and childbirth. A high percentage of cesarean sections (37.2%) were performed, which did not differ between groups. However, women in the EMDR therapy group proved seven times less likely to request an induction of labor without medical indication than women in the CAU group. There were no other significant differences between the groups in maternal or neonatal outcomes, satisfaction, or childbirth experience. EMDR therapy during pregnancy does not adversely affect pregnancy or the fetus. Therefore, therapists should not be reluctant to treat pregnant women with fear of childbirth using EMDR therapy.


Relationship between radioligand binding assay, immunoenzyme assay and immunohistochemical assay for estrogen receptors in human breast cancer and association with tumor differentiation.
We have studied the merit of a new enzyme immunoassay (EIA) in relation to the results obtained with a conventional dextran-coated charcoal assay (DCC) of estrogen receptors (ER) in cytosols and nuclear extracts of human breast cancer tissue. The results of the two assays were related to cytosolic progesterone receptor content (PgR), semiquantified ER content in formalin-fixed paraffin embedded tissue specimens and tumor differentiation. The EIA was found stable at low cytosol protein concentrations (0.5 mg/ml). The EIA and DCC assays were highly correlated both in cytosols (r = 0.92, n = 57) and nuclear extracts (r = 0.82, n = 25), but the EIA slightly overestimated the ER values in both ER fractions. A significant correlation between ER in nuclear (ER(N] and cytosolic (ER(C] fractions was established with both assays (DCC: r = 0.90, n = 56; EIA: r = 0.83, n = 24). A qualitative relationship was established between PgR and ER fractions as determined with both assays, the best quantitative association was between PgR and ER(N(DCC] (r = 0.58, n = 34, P less than 0.001). A significant qualitative and quantitative relationship was found between semiquantified ER content in formalin-fixed, paraffin-embedded tissue and ER(C(DCC] (r = 0.88), ER(N(DCC] (r = 0.86], ER(C(EIA] (r = 0.60), ER(N(CIA] (r = 0.64) and PgR (r = 0.65). Finally, we found tumor differentiation to be significantly associated with ER content as determined with all assays except for ER(N(EIA]. We recommend the use of the DCC assay for routine analysis of ER until the clinical correlation of EIA results has been established.


[Clinical trial of T-1982 (cefbuperazone) in children].
T-1982 (cefbuperazone) was administered to 20 patients with various infections by intravenous injection. The therapeutic efficacy was excellent in 13 cases, good in 6 and poor in 1, the efficacy rate being 95%. As for side effects, slight elevation of GOT and GPT was observed in 1 case, but disappeared soon after discontinuation of the therapy.


The role of small intraprotein cavities in the catalytic cycle of bacteriorhodopsin.
The last phase of the proton transfer cycle of bacteriorhodopsin calls for a passage of a proton from D38 to D96. This reaction utilizes a narrow shaft approximately 10-A long that connects the two carboxylates that cross through a very hydrophobic domain. As the shaft is too narrow to be permanently hydrated, there are two alternatives for the proton propagation into the channel. The proton may propagate through the shaft without solvation at the expense of a high electrostatic barrier; alternatively, the shaft will expand to accommodate some water molecules, thus lowering the Born energy for the insertion of the charge into the protein (B. Schätzler, N. A. Dencher, J. Tittor, D. Oesterhelt, S. Yaniv-Checover, E. Nachliel, and G. Gutman, 2003, BIOPHYS: J. 84:671-686). A comparative study of nine published crystal-structures of bacteriorhodopsin identified, next to the shaft, microcavities in the protein whose position and surrounding atoms are common to the reported structures. Some of the cavities either shrink or expand during the photocycle. It is argued that the plasticity of the cavities provides a working space needed for the transient solvation of the shaft, thus reducing the activation energy necessary for the solvation of the shaft. This suggestion is corroborated by the recent observations of Klink et al. (B. U. Klink, R. Winter, M. Engelhard, and I. Chizhov, 2002, BIOPHYS: J. 83:3490-3498) that the late phases of the photocycle (tau >/=1 ms) are strongly inhibited by external pressure.


Clustering effects of chronic obstructive pulmonary disease specific quality of life in hospitalized patients.
The primary aim of treatments for COPD is to improve health-related quality of life. However, little is known of the clustering effects related to health-related quality of life as an outcome measure. If clustering effects are observed, these have important implications for sample size estimates when cluster randomization is used in interventional studies. This study aimed to determine the intracluster correlation coefficient (ICC) of the quality of life, between hospitals for COPD patients. The Dyspnoea Impact and Symptoms Questionnaire was administered to 100 COPD inpatients from four public hospitals (25 from each) around metropolitan Melbourne, selected on the basis that they had not had any major programs implemented within the last 2 years that aimed to improve the management of COPD. Data were collected concerning demographic and socioeconomic variables and comorbidities. The highest ICC value for a health-related quality of life subscale was 0.02 (psychological score), while the highest for a symptom-based subscale was 0.04. There is minimal clustering effect of quality of life in COPD patients between the hospitals studied. Despite this, when using a cluster randomised design the sample size needed to detect the same effect as a study using simple randomisation could be inflated by up to 183%. If cluster randomization is required, the average cluster size should be kept as small as possible to negate this effect.


A technique for intracisternal collection and administration in a rhesus macaque.
Accessing the subarachnoid space via intrathecal needle placement can be done in nonhuman primates (NHPs) and other species to collect cerebral spinal fluid (CSF) or to deliver agents into the CSF. Researchers can use a variety of techniques for intrathecal collection and administration. Drawing on various published resources and previous experience with intracisternal CSF sampling, the authors sought to modify one collection technique to include CSF administration. Here, the authors describe how they collected CSF from the cisterna magna of rhesus macaques (Macaca mulatta) and administered substances through the cisterna magna into the CSF. They identify potential concerns that they had when developing the technique and describe how they alleviated those concerns. The authors found this technique, which relies heavily on teamwork, to be an effective method for intracisternal injection of an experimental compound.


Ultrasound biomicroscopic characteristics of the anterior segment in primary congenital glaucoma.
To evaluate qualitatively and quantitatively ultrasound biomicroscopic (UBM) features of the anterior segment in eyes with primary congenital glaucoma. UBM of 45 eyes of patients with primary congenital glaucoma (39 previously operated and 6 unoperated eyes) and 28 control eyes were included in this study. UBM parameters were correlated with ocular biometry. Iris thickness, ciliary body thickness, ciliary body-lens distance, posterior chamber depth, and anterior chamber angle were measured and compared with control eyes. Other features of the anterior segment were qualitatively evaluated. A thin, stretched-out ciliary body and abnormal tissue at the iridocorneal angle were features seen in 90% of UBM scans. Iris thickness and stretched zonules correlated with the axial length (r = -0.6 and 0.58, respectively; p = 0.04) but not with the mean corneal diameter. Abnormal insertion of the ciliary body to the posterior surface of the iris was noted in eight eyes (17%). The present study documents characteristic anterior segment dysplasia and ciliary body anomalies in patients with primary congenital glaucoma.


Chromium oxalate: a new spin label broadening agent for use with thylakoids.
Potassium tris(oxalato)chromate(III) trihydrate (chromium ixalate) has been shown to be a more useful broadening agent than potassium ferricyanide for the spin label 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amine (Tempamine) in thylakoid suspensions. Our data show that chromium oxalate is less permeable than ferricyanide, does not inhibit thylakoid electron transport or photophosphorylation, and is not photoreduced by thylakoids.


Who drives carbon emissions and what emission reduction potential in the resource curse agglomeration: a case of Xinjiang.
The primary problem in achieving carbon emission reduction and carbon peak is to identify the key driving factors and emission reduction potential of the industrial sector, especially in resource-cursed regions like Xinjiang. This study aimed to explore the key driving factors and abatement potential of carbon emissions based on the "energy-environment-economy" hybrid input-output model of Xinjiang during 1997-2017. The result showed that: (1) Industrial carbon emissions have experienced three stages: slow growth-rapid growth-stable growth. (2) Demand change effect and energy intensity effect were the determinants of Xinjiang industrial carbon emission change; Capital formation and domestic trade were the biggest drivers of carbon emissions growth; Especially after entering the "new normal",the driving force of imports in Xinjiang's international trade increased gradually over time. (3) The coal-based energy structure was both the biggest obstacle and the best entry point in carbon emission reduction. (4) Of the 28 key industry sectors, heavy industry including the production and supply of electricity and heat (S22), petroleum processing, coking and nuclear fuel processing (S11), chemical industry (S12), metal smelting and rolling (S14), and energy industries had the greatest potential for carbon reduction. The research findings provide scientific decision-making reference for Xinjiang to accurately grasp the carbon emission reduction potential of the industry and formulate a targeted carbon peak action plan.


Lipid peroxidation and active calcium transport in inside-out vesicles of red blood cells from preeclamptic women.
We previously reported that in preeclampsia Ca-ATPase activity diminishes about 50% in red blood cells, myometrium and syncitiotrophoblast plasma membranes. In this work, we measured the active Ca++ uptake by inside-out vesicles of human red blood cells from preeclamptic and normotensive pregnant women. Active calcium uptake by the vesicles was diminished by 49+/-3% in the preeclamptic women as compared to the gestational controls ( 8.06 +/- 0.11 nmol Ca++/mg protein min, gestational controls; 4.08 +/- 0.1 nmol Ca++/mg protein min, preeclamptics). This lowered calcium uptake correlates well with the lowered Ca-ATPase activity found in the red blood cells ghosts of the preeclamptic women (17.05 +/- 0.96 nmol Pi/mg protein min, gestational controls; 8.85 +/- 0.45 nmol Pi/mg protein min, preeclamptics). The reduced calcium uptake and Ca-ATPase activity of the red cell membranes both appear to be associated with a high level of lipid peroxidation. Thus there is a diminution in the active transport of calcium in the red blood cells of preeclamptic women. If this also occurs in other cell types of the preclamptic women, it could result in an increase in their cytosolic calcium concentration which might be responsible, in part, for some of the symptoms of this disease.


Strategies for improving the physiological relevance of human engineered tissues.
This review examines important robust methods for sustained, steady-state, in vitro culture. To achieve 'physiologically relevant' tissues in vitro additional complexity must be introduced to provide suitable transport, cell signaling, and matrix support for cells in 3D environments to achieve stable readouts of tissue function. Most tissue engineering systems draw conclusions on tissue functions such as responses to toxins, nutrition, or drugs based on short-term outcomes with in vitro cultures (2-14 days). However, short-term cultures limit insight with physiological relevance because the cells and tissues have not reached a steady-state.


Simultaneous detection of seven mutations with seven forward primers and one common reverse primer in a single PCR step.
A new PCR method is described here to amplify simultaneously several fragments sharing the same template in a single PCR step with a hemi-primer. Using this method, we successfully detected various point mutations in tissue plasminogen activator (tPA) mutants.


Bioactive carbazole alkaloids from Murraya koenigii (L.) Spreng.
Four new carbazole alkaloids (1-4) and fourteen known carbazole alkaloids (5-18) were isolated from Murraya koenigii. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 4, 6, 16, and 17 (10 μM) had moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage. Compounds 11, 12 and 18 showed significant PTP1B inhibitory activity with IC50 values of 1.773, 1.875 and 2.286 μM, respectively.


Effects of two benzodiazepine inverse agonists, RO 15-4513 and FG 7142, on recovery from pentobarbital and halothane anesthesia in the rat.
A new class of drugs, the benzodiazepine inverse agonists, have recently been shown to antagonize some of the behavioral and sedative effects of benzodiazepines, barbiturates, and alcohol. Preliminary studies suggested that at least one of these drugs, RO 15-4513, may also be able to reverse the general anesthetic properties of volatile halogenated agents. Another inverse agonist, FG 7142, exhibits a similar ability to antagonize alcohol or benzodiazepines. However, FG 7142 is less potent than RO 15-4513 and has less affinity for the benzodiazepine receptor (BZR). The present studies were therefore undertaken to compare the analeptic effects and relative potencies of RO 15-4513 and FG 7142 on the anesthetic properties of pentobarbital compared with the general anesthetic agent halothane as measured by the time for recovery of the righting reflex in the rat. Three basic experimental paradigms were employed. Drug (FG or RO) or carrier was administered 5 minutes prior to the induction of pentobarbital anesthesia. Drug or carrier was administered to anesthetized animals 60 minutes after pentobarbital injection. Lastly, drug or carrier was administered 5 minutes prior to 15 minutes of halothane anesthesia. In addition, the selective benzodiazepine antagonist, flumazenil (RO 15-1788), was used to determine if the effects of the benzodiazepine inverse agonists on recovery from barbiturate or halothane anesthesia were due to activity at the BZR. The results revealed that RO was both more potent and more effective than FG at speeding recovery from barbiturate anesthesia in the rat. RO's effects appeared to be primarily due to BZR inverse agonist activity since it could be reversed by the BZR antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)


Embracing Islam in Switzerland: (Re-)Conversion Between Searching for the Meaning of Life and Social Ties.
The pioneer conversion model of Lofland and Stark suggests that people adopt a religion because experiences in their biography motivate them to seek answers regarding the purpose of life, and because they encounter followers of a religion that happens to provide them with convincing answers. We draw on the Lofland-Stark model while considering Lofland's and Skonovd's concept of conversion motifs to gain a deeper insight into the convert's story of adopting a new faith. Furthermore, we integrate Paloutzian's concept of spiritual transformation into our theoretical framework to cover both conversion and reconversion (reversion). Against this conceptual background and applying a combination of narrative-autobiographical interviews with qualitative network analysis, we interviewed 24 converts and reconverts in Switzerland. Based on the findings, we propose a typology along the dimensions of "seeking answers" and "social contacts".


Importance of size, sulfation, and anticoagulant activity in the potentiation of acidic fibroblast growth factor by heparin.
Heparin was previously reported to potentiate the mitogenic activity of endothelial cell mitogens in a crude extract of bovine hypothalami (Thornton, S. C., Mueller, S. N., and Levine, E. M. (1983) Science 222, 623-625). We and others (Gospodarowicz, D., and Cheng, J. (1986) J. Cell. Physiol. 128, 475-484) have reported that the growth stimulatory effects of acidic fibroblast growth factor (aFGF) are potentiated in a similar manner. We have used these observations as the basis of an assay to characterize the importance of size, sulfation, and anticoagulant activity of heparin in mediating this effect. Partial nitrous acid depolymerization of heparin from porcine intestinal mucosa resulted in a mixture of heparin fragments, containing oligosaccharides ranging from disaccharides to polysaccharides of about 40 monosaccharides in length. This mixture was fractionated by ion exchange chromatography and gel permeation chromatography to obtain size-homogeneous oligosaccharides with different degrees of sulfation. Assay of these heparin-derived saccharides in the presence of a suboptimal concentration of aFGF revealed that a minimum chain length and a certain degree of sulfation is required in order to potentiate the action of aFGF. Low sulfate oligosaccharides (4-16 units) were unable to potentiate aFGF, whereas medium sulfate fractions of octadecasaccharides and larger were able to moderately potentiate aFGF. The potentiation of aFGF by the high sulfate fraction correlated with the saccharide size: 12 or more monosaccharide units were necessary to achieve potentiation equivalent to whole heparin, octa- and decasaccharides were mildly stimulatory, and hexasaccharides were without effect. In the absence of aFGF, intact heparin as well as all the oligosaccharides examined, inhibited the proliferation of capillary endothelial cells to approximately the same degree, between 20 and 50% inhibition. When a tetradecasaccharide was separated into a binding and a nonbinding fraction on matrix-bound antithrombin III, no difference was seen for these fractions in the endothelial cell proliferation assay. These results indicate that both size and sulfation of a heparin-derived oligosaccharide contribute to its ability to interact with aFGF and/or endothelial cells and that this interaction is independent of anticoagulant activity. In addition, our findings suggest that the inhibitory and potentiating effects of heparin on capillary endothelial cells have different structural requirements.


Role of bypass surgery and balloon occlusion test for the endovascular management of fusiform dissecting aneurysms. Report of two cases.
Fusiform intracranial aneurysm is one of the most difficult pathologies to treat. The role and efficacy of recent advanced endovascular technique and conventional bypass surgery are discussed.


Proximal relationships between social support and PTSD symptom severity: A daily diary study of sexual assault survivors.
In cross-sectional studies, social support and posttraumatic stress disorder (PTSD) symptoms appear related, in that higher severity of PTSD is associated with lower social support and vice versa. Theoretical models of the causal direction of this relationship differ. Most longitudinal studies suggest that PTSD symptoms erode social support over time, although some suggest that higher social support is prospectively associated with decrease in PTSD symptom severity. It is unclear, though, how social support and PTSD affect each other in the short term. The purpose of this study was to test day-to-day relationships between PTSD and social support to elucidate how PTSD and social support influence each other. Using 1173 daily observations from 75 college women who met screening criteria for lifetime sexual assault and past-month PTSD, this study tested same-day and next-day relationships between PTSD and social support using mixed models. Within-person analyses indicated that, when PTSD was higher than usual on a given day, social support was higher the next day. Between-person analyses suggested that people with generally higher social support tended to have lower PTSD symptoms on a given day, but average PTSD symptom severity was not associated with day-to-day fluctuations in social support. Rather than eroding in response to daily symptoms, social support might be sought out following increases in PTSD, and when received consistently, might reduce symptoms of PTSD in the short term. Interventions that increase college women's access to social support after sexual assault may thus be helpful in addressing PTSD.


The opiate-like action of tilidine is mediated by metabolites.
The analgesic effect of tilidine in rats is completely antagonized by the narcotic antagonist naloxone. Radioreceptor assays revealed, however, that the main metabolites of tilidine, nortilidine and bisnortilidine, rather than tilidine exhibit affinity to opiate receptors. These findings were confirmed in studies using the electrically stimulated guinea pig ileum and the mouse vas deferens. Chronic tilidine administration to rats caused a considerable degree of physical dependence, which was expected from the ability of the intact animal to metabolize tilidine. In the isolated ileum from chronically morphinized guinea pigs, both nortilidine and bisnortilidine fully substituted for morphine in preventing induction of withdrawal, indicating dependence liability of these metabolites.