Diabetes outcomes in the Indian health system during the era of the Special Diabetes Program for Indians and the Government Performance and Results Act.
We reviewed changes in blood glucose, blood pressure, and cholesterol levels among American Indians and Alaska Natives between 1995 and 2001 to estimate the quality of diabetes care in the Indian Health Service (IHS) health care delivery system. We conducted a cross-sectional analysis of data from the Indian Health Service Diabetes Care and Outcomes Audit. Adjusted mean Hemoglobin A1c (HbA1c) levels (7.9% vs 8.9%) and mean diastolic blood pressure levels (76 vs 79 mm Hg) were lower in 2001 than in 1995, respectively. A similar pattern was observed for mean total cholesterol (193 vs 208 mg/dL) and triglyceride (235 vs 257 mg/dL) levels in 2001 and 1995, respectively. We identified changes in intermediate clinical outcomes over the period from 1995 to 2001 that may reflect the global impact of increased resource allocation and improvements in processes on the quality of diabetes care, and we describe the results that may be achieved when community, health program, and congressional initiatives focus on common goals.


Cell-to-cell contacts in primary cultures of dissociated chicken embryonic brain.
The fine structure of intercellular contacts was studied in primary cultures prepared from chicken embryonic brain. Desmosomes were frequently seen between the glial cells. Synaptic contacts were observed among neuronal cell bodies and neural processes after 8 days in vitro. Gap junctions were revealed between glial elements suggesting a functional role in direct cell communication and providing a morphological basis for previous observations on potassium transport in cultures of dissociated brain cells.


Early and midterm results of single-port video-assisted thoracoscopic sympathectomy.
Video-assisted thoracoscopic sympathectomy (VATS) is the gold standard for patients with hyperhidrosis of the upper limbs. The primary aim of this retrospective study was to evaluate the midterm outcome and the degree of satisfaction of patients who underwent single-port VATS. Forty three patients diagnosed with hyperhidrosis underwent T3, T4 VATS single-port approach, between January 2009 and May 2011. Early and midterm outcome with particular emphasis on patient satisfaction were collected by hospital chart and telephonic interview. The mean follow-up was 14 months. No major perioperative complication occurred except for chylothorax in a case. During the immediate postoperative period, all the patients reported palmar anhydrosis. Compensatory sweating (6.9%) and recurrence of hyperhidrosis (6.9%) are responsible mainly for dissatisfaction. No patients experienced moderate or severe chronic pain. Single-port VATS is a feasible and minimally invasive technique with a low incidence of chronic pain for the treatment of hyperhidrosis. A few patients may experience compensatory sweating and recurrence of hyperhidrosis. The degree of patient satisfaction with the midterm surgical results is high.


Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via Jun proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2.
Vasohibin 2 (VASH2) has previously been identified as an agiogenenic factor and a cancer related protein. Here we investigated the association of VASH2 expression and chemoresistance in pancreatic cancer. Immunohistochemical staining for VASH2 was performed on 102 human pancreatic cancer samples. Pancreatic cancer cell line models exhibiting overexpression or knockdown of VASH2 were generated. Gene expression analyses were carried out to determine genes differentially regulated by VASH2. Putative transcription factors that are downstream mediators of gene expression regulated by VASH2 were queried bioinformatically. Dual-luciferase reporter assays and ChIP assays were performed to confirm transactivation of target genes following VASH2 overexpression or knockdown. VASH2 protein expression was higher in human pancreatic cancer than in paired adjacent tissues and elevated VASH2 levels were associated with gemcitabine chemoresistance. In cell line models of pancreatic cancer, VASH2 expression induced gemcitabine chemoresistance in vitro and in vivo. It was discovered that expression of ribonucleotide reductase regulatory subunit M2 (RRM2) is regulated by VASH2; immunohistochemical analysis demonstrated a positive association of VASH2 expression and RRM2 expression in human pancreatic cancer tissues. Bioinformatics analyses revealed that induction of the Jun proto-oncogene (JUN) by VASH2 is responsible for upregulation of RRM2 expression; this JUN-dependent regulation of RRM2 by VASH2 was confirmed by chromatin immunoprecipitation and dual luciferase reporter assays, which demonstrated that JUN directly binds with the RRM2 promoter to activate transcription. These data suggest that VASH2 reduces the chemosensitivity to gemcitabine in pancreatic cancer cells via JUN-dependent transactivation of RRM2.


Increased heat production proportional to oxygen consumption in human neutrophils activated with phorbol-12-myristate-13-acetate.
The heat produced by neutrophils was measured with a flow microcalorimeter. 02 consumption, ATP concentration, lactic acid production and 14CO2 production from oxidation of [1-(14)C]-glucose [6-(14)C]-glucose and [U-14C]-glucose were evaluated. Experiments were also carried out in the presence of the metabolic inhibitors, N-ethylmaleimide and NaF. Heat effects were correlated to the enthalpy change of aerobic and anaerobic glucose catabolism. Two different heat contributions related to two different nonmitochondrial 02 reduction pathways are present during the metabolic burst. Theoretical and experimental data indicate that the reducing power is derived from the catabolism of glucose both through the hexose monophosphate shunt and glycolysis.


The mechanism of hydrogen evolution in Cu(bztpen)-catalysed water reduction: a DFT study.
The mechanism of water reduction catalysed by a mononuclear copper complex Cu(bztpen) (bztpen = N-benzyl-N,N',N'-tris(pyridine-2-ylmethyl)ethylenediamine) has been elucidated by DFT calculations, revealing that hydrogen evolution proceeds via coupling of a Cu(ii)-hydride and a pendant pyridinium, and providing important implications for the future design of new catalytic systems for water reduction.


The continuing quest for parity: HBCU nursing students' perspectives on nursing and nursing education.
The benefits of a diverse nursing workforce are well-recognized, yet, the attainment of a sustainable, competent and diverse nursing workforce continues to be a global challenge. In this qualitative study, we describe nursing students' perceptions on nursing and nursing education at a Historically Black College/University (HBCU). Focus groups were conducted with 16 graduate and undergraduate nursing students. Four themes emerged: communication, lack of resources, support systems and professional socialization. Mentoring and civility were identified as factors important to enhance a diverse workforce.


Nurse-Led Phone Call Follow-Up Clinics Are Effective for Patients With Prostate Cancer.
The rising cost of healthcare requires rethinking in terms of resource utilisation care delivery. Nurse-led PSA phone follow-up clinics may provide a suitable option. 815 patients were recruited for the nurse-led stable prostate cancer telephone follow-up service. A convenience sample was selected for postal questionnaire assessment of their satisfaction. 815 patients had 3683 phone-call follow ups over 10 years. Patients' own understanding of condition varied from average (76.3%) and good (9.2%) in the majority. 87.2% found the service convenient and 75.6% informative. 95.3% found the telephone assessment preferable to attending the outpatient department. 87.2% were keen on savings on transport/travel. 53.5% found it more reassuring. 91.9% of patients felt that everything they wanted to talk about was covered. This service can be delivered in a high volume nurse-led service, with high levels of patient satisfaction, as an innovative service development.


The expression and localization of selected matrix metalloproteinases (MMP-2, -7 and -9) and their tissue inhibitors (TIMP-2 and -3) in follicular cysts of sows.
Matrix metalloproteinases (MMPs) are a family of enzymes that degrade extracellular matrix (ECM) molecules, playing a vital role in tissue remodeling under physiological and pathological conditions. Their expression and/or activity are regulated by specific tissue inhibitors of MMPs named TIMPs. Recently, an imbalance in the MMP/TIMP system has been found in human and bovine ovarian cysts, but its role in porcine cyst pathogenesis is unknown. This study examined mRNA expression, protein abundance and localization for selected members of the MMP/TIMP system in follicular cysts of sows. Based on histological analysis, we have assessed follicular (FC) and follicular lutein (FLC) cysts with preovulatory follicles (PF) used as a control. Regarding the pattern of MMP expression, increased MMP2, MMP7 and MMP9 mRNA levels were observed in FLC. Furthermore, both pro- and active forms of MMP-2 and MMP-9 proteins were more abundant in FLC. In FC, the abundance of latent and active forms of MMP-9 and the active form of MMP-2 were greater when compared with PF. In relation to TIMPs, TIMP-2 mRNA and protein expression were increased in FLC, whereas TIMP-3 was up-regulated in both FC and FLC only at the protein level. Using immunofluorescence, MMP-2, MMP-7, TIMP-2 and TIMP-3 were detected in granulosa and theca compartments of FC and within the entire luteinized wall of FLC. Notably, MMP-9 occurred weakly in the granulosa layer of FC, but abundantly in the theca compartment of FC and in the luteinized FLC. Taken together, our findings indicate altered expression of the MMP/TIMP system, suggestive of increased ECM degradation, in sow follicular cysts. These components may be involved in the pathogenesis of porcine ovarian cysts through the ECM remodeling.


Inorganic Polyphosphate and Cancer.
This review presents data on the relationship between inorganic polyphosphate metabolism and carcinogenesis including participation of polyphosphates in the regulation of activity of mTOR and other proteins involved in carcinogenesis, the role of h-prune protein (human polyphosphatase) in cell migration and metastasis formation, the prospects for using polyphosphates and inhibitors of polyphosphate metabolism enzymes as agents for controlling cell proliferation and migration.


Top-down and bottom-up attention to memory: a hypothesis (AtoM) on the role of the posterior parietal cortex in memory retrieval.
Recent neuroimaging studies have implicated the posterior parietal cortex in episodic memory retrieval, but there is uncertainty about its specific role. Research in the attentional domain has shown that superior parietal lobe (SPL) regions along the intraparietal sulcus are implicated in the voluntary orienting of attention to relevant aspects of the environment, whereas inferior parietal lobe (IPL) regions at the temporo-parietal junction mediate the automatic allocation of attention to task-relevant information. Here we propose that the SPL and the IPL play conceptually similar roles in episodic memory retrieval. We hypothesize that the SPL allocates top-down attention to memory retrieval, whereas the IPL mediates the automatic, bottom-up attentional capture by retrieved memory contents. By reviewing the existing fMRI literature, we show that the posterior intraparietal sulcus of SPL is consistently active when the need for top-down assistance to memory retrieval is supposedly maximal, e.g., for memories retrieved with low vs. high confidence, for familiar vs. recollected memories, for recognition of high vs. low frequency words. On the other hand, the supramarginal gyrus of IPL is consistently active when the attentional capture by memory contents is supposedly maximal, i.e., for strong vs. weak memories, for vividly recollected vs. familiar memories, for memories retrieved with high vs. low confidence. We introduce a model of episodic memory retrieval that characterizes contributions of posterior parietal cortex.


Frequency of cystoid macular edema and vitreomacular interface disorders in genetically solved syndromic and non-syndromic retinitis pigmentosa.
Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP). Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05. We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2-1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01). We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.


Decreased Root-Knot Nematode Gall Formation in Roots of the Morning Glory Ipomoea tricolor Symbiotic with Ergot Alkaloid-Producing Fungal Periglandula Sp.
Many species of morning glories (Convolvulaceae) form symbioses with seed-transmitted Periglandula fungal endosymbionts, which produce ergot alkaloids and may contribute to defensive mutualism. Allocation of seed-borne ergot alkaloids to various tissues of several Ipomoea species has been demonstrated, including roots of I. tricolor. The goal of this study was to determine if infection of I. tricolor by the Periglandula sp. endosymbiont affects Southern root-knot nematode (Meloidogyne incognita) gall formation and host plant biomass. We hypothesized that I. tricolor plants infected by Periglandula (E+) would develop fewer nematode-induced galls compared to non-symbiotic plants (E-). E+ or E- status of plant lines was confirmed by testing methanol extracts from individual seeds for endosymbiont-produced ergot alkaloids. To test the effects of Periglandula on nematode colonization, E+ and E- I. tricolor seedlings were grown in soil infested with high densities of M. incognita nematodes (N+) or no nematodes (N-) for four weeks in the greenhouse before harvesting. After harvest, nematode colonization of roots was visualized microscopically, and total gall number and plant biomass were quantified. Four ergot alkaloids were detected in roots of E+ plants, but no alkaloids were found in E- plants. Gall formation was reduced by 50% in E+ plants compared to E- plants, independent of root biomass. Both N+ plants and E+ plants had significantly reduced biomass compared to N- and E- plants, respectively. These results demonstrate Periglandula's defensive role against biotic enemies, albeit with a potential trade-off with host plant growth.


Mutations at specific atp6 codons which cause human mitochondrial diseases also lead to male sterility in a plant.
Defects in the human mitochondrial genetic system result in some diseases. These disorders are the result of rearrangements or point mutations in mitochondrial genes. In higher plants mutations and rearrangements in the mitochondrial DNA are believed to cause cytoplasmic male sterility (CMS), a mitochondrially inherited inability to produce viable pollen. In sorghum, formation of CMS is strongly correlated with anther-specific loss of mitochondrial atp6 RNA editing. Here we show that this loss of atp6 RNA editing mimics point mutations at codons that cause severe disorders in humans. We conclude that (i) loss of RNA editing in sorghum anthers probably causes CMS, (ii) similarities exist in the onset of mitochondrial dysfunction in plant and human tissues, and (iii) the evolutionary appearance of RNA editing provided a mechanism to compensate for otherwise lethal point mutations.


Trapezio-metacarpal arthroplasty by total prosthesis.
Thirty-four total trapezio-metacarpal prostheses have been fitted since 1971. Twenty-eight have had a follow-up for more than six months (up to a maximum of five years) and allow a valid assessment of the situation. The operations were undertaken for rheumatoid, osteoarthritic disease, and following trauma. The reasons were either pain, mechanical instability, or stiffness. Two out of three times results were good. The best results were obtained for pain and stability. Those where the indication was stiffness were less satisfying. There were five cases of loosening of the trapezial cup due to operative errors. The mediocre results in general are caused by incomplete treatment allowing an associated lesion to develop. Greater strictness in the indications and in carrying out of operation ought to ensure better results.


Proteomic analysis of HIV-1 Gag interacting partners using proximity-dependent biotinylation.
The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is necessary and sufficient to assemble non-infectious particles. Given that HIV-1 subverts many host proteins at all stages of its life cycle, it is essential to identify these interactions as potential targets for antiretroviral therapy. This work demonstrates the use of proximity-dependent biotin identification (BioID) of host proteins and complexes that are proximal to the N-terminal domains of the HIV-1 Gag polyprotein. Two of the hits identified in the BioID screen were validated by immunoprecipation and confirmed the interaction of DDX17 and RPS6 with HIV-1 Gag. Our results show that BioID is both a successful and complementary method to screen for nearby interacting proteins of HIV-1 Gag during the replicative cycle in different cell lines.


Assessing the cytoskeletal system and its elements in C6 glioma cells and astrocytes by atomic force microscopy.
To investigate how the characteristic structure of the cytoskeleton in glioma cells is associated with invasiveness. The whole cytoskeletal system was characterized by atomic force microscopy (AFM), while single cytoskeletal elements were exhibited by AFM and using cytoskeletal protein inhibitors to inhibit microfilaments or/and microtubules and displayed by immunofluorescence microscopy. The fluorescence intensity of F-actin was measured by flow cytometry and the structural difference between C6 glioma cells and astrocytes was studied. Cytoskeletons in both cells presented network structures, however, the C6 glioma cells showed an irregular edge root and their microfilaments were creber and dense. Intermediate filaments were extensive network structure with non-polarized multipoint connections. The microtubules were relatively big and long and formed tight bundles with close connections between bundles. Astrocytes had a regular and smooth edge, with sparse microfilaments, while the intermediate filaments were dense and interwoven and the microtubules were dense bundled, but only loosely connected each other. Besides, the fluorescence intensity of F-actin was significantly higher in C6 glioma cells (202.54 +/- 11.06) than in the astrocytes (62.64 +/- 10.23), P < 0.01. Whole cytoskeleton and its elements of C6 cells were disclosed of characteristic structures associated with invasiveness. Meanwhile, the content of F-actin could be used as a parameter for measuring cell invasiveness.


Environmental stress, minority status, and local poverty: risk factors for mental health in Berlin's inner city.
This study examines whether climate change-associated environmental stressors, including air and noise pollution, local heat levels, as well as a lack of surrounding greenspace, mediate the effects of local poverty on mental health, using the 28-item General Health Questionnaire. We recruited 478 adults who were representative of eleven of Berlin's inner-city neighborhoods. The relationship of individual-level variables, neighborhood-level sociodemographic and environmental data from the Berlin Senate (Department for Urban Development, Building and Housing) to mental health was assessed in a multilevel model using SPSS. We found that neither local exposure to environmental stressors, nor available greenspace as a protective factor, mediated the effects of local poverty on variance in mental health (all p values > 0.2). However, surrounding greenspace (r = -0.24, p < 0.001), nitrogen dioxide levels (r = 0.10, p < 0.05), noise pollution (rho = 0.15, p < 0.01), and particle pollution (r = 0.12, p < 0.001) were associated with local poverty, which, more strongly than individual factors, accounted for variance in mental health (β = 0.47, p < 0.001). Our analysis indicates that the effects of local poverty on mental health are not mediated by environmental factors. Instead, local poverty was associated with both an increased mental health burden and the exposure to climate-related environmental stressors.


Severe Asthma and the Primary Care Provider: Identifying Patients and Coordinating Multidisciplinary Care.
Without proper care, patients with severe forms of asthma face substantial medical risks, marked reductions in quality of life, and other significant disease-related burdens. Therefore, it is essential that primary care clinicians and other healthcare providers are adept at identifying cases of severe asthma on the basis of symptom control, exacerbation risks, and the need for relatively aggressive treatment regimens (eg, high-dose inhaled corticosteroids with long-acting controller medications or frequent oral corticosteroid use). Engaging and educating affected individuals as part of ongoing treatment planning are best achieved with a good understanding of patients' own insights into their disease and management challenges that often arise in busy healthcare practices. This includes effectively communicating with patients about the implications of their diagnosis and potential treatment strategies that can be accessed via coordinated multidisciplinary care. Expert primary care and specialist faculty have highlighted strategies to identify cases of severe asthma, appropriate referral pathways for these individuals, and considerations on integrating patients' perspectives into clinical decision making across the continuum of care (access to an accredited educational program on these topics is available at http://courses.elseviercme.com/pcp/687). Additionally, this online program is a component of a larger platform of education activities and consolidated clinical resources designed to improve the care of patients with respiratory disorders (http://respiratorycme.elsevierresource.com/).


Spectrophotometric quantitation of peroxidase-stained protein bands following gel electrophoresis and the western blot transfer technique with respiratory syncytial virus.
A procedure is described for spectrophotometrically measuring the position and intensity of ELISA-stained protein bands after western blot analyses. Partially purified virus proteins separated by acrylamide gel electrophoresis and electrophoretically transblotted onto nitrocellulose paper were identified by ELISA reactions according to established procedures. The nitrocellulose paper strips were then rendered transparent on glass slides by treatment with a plastics solvent (Gelman Sepra-Clear). The slides were then scanned at 480 nm to obtain the precise migration distance and area under the curve (i.e., quantity) of each band, thus allowing accurate comparison of the proteins from different virus strains.


Differential distribution of afferents containing serotonin and neuropeptide Y within the marmoset suprachiasmatic nucleus.
Neuropeptide Y-containing fibers/terminals were immunohistochemically detected in the ventral portion of the marmoset suprachiasmatic nucleus, approximately matching the distribution of its retinal afferents. On the other hand, serotonergic fibers/terminals were found mostly in central and dorsal areas of the suprachiasmatic nucleus, almost completely sparing its ventral portion. These data may represent a morphological substrate for differential actions of serotonin and neuropeptide Y in the control of circadian rhythmicity in marmosets.


Epidemiology of human exposure to ultrasound: a critical review.
Epidemiologic studies and surveys and widespread clinical usage over 25 years have yielded no evidence of any adverse effect from diagnostic ultrasound. Nonetheless, the inability to find convincing proof of an effect, either from epidemiology or from physicians' experience, does not preclude the possibility of it happening. Statistical reasoning shows that even with large population studies, it is difficult to identify a small increase in the rate of a commonly occurring event. Subtle effects, long-term delayed effects, and certain genetic effects, could easily escape detection.


Radioimmunoassay of DSIP-like material in human blood: possible protein binding.
A radioimmunoassay (RIA) for DSIP-like material was established in unextracted human plasma. Most of the immunoreactivity was found in a "large" fraction while a much smaller amount co-eluted with DSIP from Sephadex as a "free" fraction. Both peaks progressively increased with increasing amounts of added DSIP. Acidification, but not treatment with charcoal-dextran, resulted in a relative decrease in the "large" peak and an increase in the "free" peak. This RIA, therefore, appears to measure both bound and free forms of DSIP-like immunoreactivity, the levels of which were higher at 4 p.m. than at 8 a.m.


Synthesis and biological activity of glycosylated analogs of the C-terminal hexapeptide and heptapeptide of substance P.
The synthesis of two glycosylated analogs of Substance P is described. The activity of the peptides was assayed on the isolated guinea-pig ileum and their degradation was studied using rat hypothalamus slices. While glycosylation noticeably enhances the solubility of the corresponding compounds, the beta-glucopyranosyl moiety only slightly modifies the biological half-life and the bioactivity of the glycopeptides.


Plasmid-encoded initiation protein is required for activity at all three origins of plasmid R6K DNA replication in vitro.
DNA replication of plasmid R6K initiates at three unique sites, ori alpha, ori beta, and ori gamma. Replicating DNA molecules of a deletion derivative of R6K were synthesized in an in vitro system containing pi protein fraction from cells carrying a mini-R6K derivative that produced only this initiation protein as an R6K-encoded protein and analyzed by electron miscroscopy. Requirement of pi protein for the activity of all these three replication origins in vitro was verified. Frequencies of initiation at the three origins were almost equal.


Impact of donor and recipient hepatitis C status in lung transplantation.
Studies of lung transplantation in the setting of donors or recipients with hepatitis C virus (HCV) have been limited but have raised concerns about outcomes associated with this infection. Lung transplant cases in the United Network for Organ Sharing (UNOS) database from 1994 to 2011 were analyzed for the HCV status of both donor and recipient. First, among HCV-negative recipients, those who received a lung from an HCV-positive donor (HCV(+) D) were compared with those who received an HCV-negative lung (HCV(-) D). Donor, recipient and operative characteristics as well as outcomes were compared between groups, and overall survival was compared after adjustment for confounders. In a second analysis, HCV-positive recipients (HCV(+) R) were compared with HCV-negative recipients (HCV(-) R). The analysis was stratified by era (1994 to 1999 and 2000 to 2011) and long-term survival was compared. Of 16,604 HCV-negative patients in the UNOS database, 28 (0.2%) received a lung from an HCV(+) D, with use of HCV(+) D decreasing significantly over time. Overall survival (OS) was shorter in the HCV(+) D group (median survival: 1.3 vs 5.1 years; p = 0.002). Results were confirmed in adjusted analyses. After inclusion criteria were met, 289 (1.7%) of the lung transplant recipients were HCV(+) R. These patients appeared similar to their HCV(-) R counterparts, except they were older and had more limited functional status. OS was significantly lower in HCV-positive individuals during the early era (median survival: 1.7 vs 4.5 years; p = 0.004), but not the recent era (median survival: 4.4 vs 5.4 years; p = 0.100). Again, results were confirmed by adjusted analysis. HCV-positive status is a rare problem when considering both lung recipients and donors. Current data demonstrate significantly worse outcomes for HCV-negative patients receiving an HCV(+) lung; however, since 2000, HCV(+) recipients undergoing lung transplantation appear to have survival approximating that of HCV(-) recipients, an improvement from previous years. Recent medical advances in treatment for HCV may further improve outcomes in these groups.


CT-guided high-dose-rate brachytherapy in the interdisciplinary treatment of patients with liver metastases of pancreatic cancer.
CT-guided high-dose-rate brachytherapy (CT-HDRBT) is an interventional radiologic technique for local ablation of primary and secondary malignomas applying a radiation source through a brachycatheter percutaneously into the targeted lesion. The aim of this study was to assess local tumor control, safety and efficacy of CT-HDRBT in the treatment of liver metastases of pancreatic cancer. Twenty consecutive patients with 49 unresectable liver metastases of pancreatic cancer were included in this retrospective trial and treated with CT-HDRBT, applied as a single fraction high-dose irradiation (15-20 Gy) using a 192Ir-source. Primary endpoint was local tumor control and secondary endpoints were complications, progression-free survival and overall survival. The mean tumor diameter was 29 mm (range 10-73). The mean irradiation time was 20 minutes (range 7-42). The mean coverage of the clinical target volume was 98% (range 88%-100%). The mean D100 was 18.1 Gy and the median D100 was 19.78 Gy. Three major complications occurred with post-interventional abscesses, three of which were seen in 15 patients with biliodigestive anastomosis (20%) and overall 15%. The mean follow-up time was 13.7 months (range 1.4-55.0). The median progression-free survival was 4.9 months (range 1.4-42.9, mean 9.4). Local recurrence occurred in 5 (10%) of 49 metastases treated. The median overall survival after CT-HDRBT was 8.6 months (range 1.5-55.3). Eleven patients received chemotherapy after ablation with a median progression-free survival of 4.9 months (mean 12.9). Nine patients did not receive chemotherapy after intervention with a median progression-free survival of 3.2 months (mean 5.0). The rate of local tumor control was 91% in both groups after 12 months. CT-HDRBT was safe and effective for the treatment of liver metastases of pancreatic cancer.


Odontologic kinship analysis in skeletal remains: concepts, methods, and results.
Identification of familial relationships is essential for reconstructing social structures in ancient societies. In forensic medicine, individual identification is occasionally also achieved by the same procedure. The paper discusses the role of odontologic traits for kinship analysis as well as several statistical procedures helpful in the detection and evaluation of presumptive 'genetic' relationships, and presents examples of applications.


The anti-snake activity of Nectandra angustifolia flavonoids on phospholipase A2: In vitro and in silico evaluation.
Lauraceae family includes Nectandra angustifolia a species widely used in the folk medicine of South America against various maladies. It is commonly used to treat different types of processes like inflammation, pain, and snakebites. Snakes of the Bothrops genus are responsible for about 97% of the ophidic accidents in northeastern Argentina. To evaluate the anti-snake activity of the phytochemicals present in N. angustifolia extracts, identify the compounds, and evaluate their inhibitory effect on phospholipase A2 (PLA2) with in vitro and in silico assays. Seasonal variations in the alexiteric potential of aqueous, ethanolic and hexanic extracts were evaluated by inhibition of coagulant, haemolytic, and cytotoxic effects of B. diporus venom. The chemical identity of an enriched fraction obtained by bio-guided fractioning was established by UPLC-MS/MS analysis. Molecular docking studies were carried out to investigate the binding mechanisms of the identified compounds to PLA2 enzyme from snake venom. All the extracts inhibited venom coagulant activity. However, spring ethanolic extract achieved 100% inhibition of haemolytic activity. Bio-guide fractioning led to an enriched fraction (F4) with the highest haemolytic inhibition. Five flavonoids were identified in this fraction; molecular docking and Molecular Dynamics (MD) simulations indicated the binding mechanisms of the identified compounds. The carbohydrates present in some of the compounds had a critical effect on the interaction with PLA2. This study shows, for the first time, which compounds are responsible for the anti-snake activity in Nectandra angustifolia based on in vitro and in silico assays. The results obtained in this work support the traditional use of this species as anti-snake in folk medicine.


Efficacy of neoadjuvant bicalutamide and dutasteride as a cytoreductive regimen before prostate brachytherapy.
To evaluate the cytoreductive effectiveness of combined neoadjuvant bicalutamide and dutasteride before prostate brachytherapy for clinically localized prostate cancer. From April 2003 to May 2005, 31 patients opted for cytoreduction with bicalutamide (50 mg daily) and dutasteride (0.5 mg daily). Before, and at 3 months (90 +/- 5 days) after, the initiation of medical therapy, all patients underwent a transrectal ultrasound volumetric study of the prostate gland, with ellipsoid volume determination of the prostate gland and transition zone. The variables analyzed included pretreatment and posttreatment prostate and transition zone volumes and changes in width, height, and length of the prostate gland and transition zone. A multivariate analysis was performed to identify predictors for prostate gland and transition zone volume reduction. Before the initiation of bicalutamide and dutasteride, the mean prostate volume was 54.3 cm3 by planimetric summation and 49.7 cm3 by ellipsoid volume calculation. After a 3-month course of combination medical therapy, the average prostate volume was 36.1 cm3 (33.6% reduction) and 32.5 cm3 (34.6% reduction) using the volumetric and ellipsoid volume determinations, respectively. Bicalutamide and dutasteride resulted in a 39.8% reduction in transition zone volume (20.8 cm3 versus 12.4 cm3). The prostate gland and transition zone dimensions (width, height, and length) decreased about 11.4% to 19.9%. The prostate gland and transition zone volume reductions after a 3-month course of neoadjuvant bicalutamide and dutasteride are comparable to previous reports of volume reduction using a luteinizing hormone-releasing hormone agonist with or without an antiandrogen.


Genome Sequences of West Nile Virus Reference Materials.
We report the sequences of two West Nile virus (WNV) strains (lineages 1 and 2) developed by the Paul-Ehrlich-Institut as reference materials. The materials are calibrated against the 1st World Health Organization WNV RNA International Standard and are intended for use in nucleic acid technology assays supporting transfusion safety.


Long-term visual results of vitreous surgery in diabetic eye disease.
Long-term visual results in the first 124 consecutively vitrectomized eyes of 105 diabetic patients in our department were evaluated. The indications for vitrectomy were unresorbable vitreous haemorrhage (77 eyes, 62%) (group A), central traction retinal detachment (21 eyes, 17%) (group B), and a combination of both (26 eyes, 21%) (group C). Initially visual acuity (VA) improved at least by one category in 83 eyes (67%). The latest postoperative VA after the mean follow-up of 3.7 +/- 0.2 years was greater than = 0.3 in 36 eyes (29%), 0.1-0.25 in 15 eyes (12%), 0.05-0.08 in 9 eyes (7%), counting fingers (CF) 1-less than 3 m in 13 eyes (11%), and less than CF 1 m in 51 eyes (41%). The latest VA of 0.3 or better was significantly more common in group A (40%) than in group B (10%) or group C (12%) (P = 0.0087 and 0.0076, respectively). The most common causes of visual failure (VA less than C F 1m) were neovascular glaucoma and/or retinal detachment. At the latest follow-up visit 50% of the patients had VA of 0.3 or better, 16% were in the low-vision category, and 34% were blind (VA less than 0.05).


Endomyocardial substrate of ventricular arrhythmias in patients with autoimmune rheumatic diseases.
Delayed enhancement-magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n = 11) or frequent ventricular extrasystoles (n = 9) underwent DE-MRI and/or endocardial electroanatomical mapping of the left ventricle (LV). Ten patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.


Pediatric Extraskeletal Ewing Sarcoma Originating in the Heart: A Case Report and Review of the Literature.
Extraosseous Ewing sarcoma of primary cardiac origin is an extremely rare variety among pediatric cardiac neoplasms. We report a case of extraosseous Ewing sarcoma of primary cardiac origin in a 9-year-old girl, treated with debulking surgery, adjuvant chemotherapy, and radiotherapy.


Comparison of the effectiveness of alkaline and enzymatic extraction and the solubility of proteins extracted from carbohydrate-digested rice.
Carbohydrate-digested rice (CDR) residue, the production waste of electrolyte drinks, contains high levels of proteins (approximately 50% of dry matter). Methods for effectively extracting protein from CDR were investigated in this study by comparing alkaline and enzymatic extraction. Alkaline extraction was performed using different concentrations of sodium hydroxide (NaOH). Enzymatic extraction was performed with either commercial Alcalase® or Flavourzyme®. Protein recovery and solubility, and total soluble protein obtained via each method were compared to determine extraction effectiveness. In addition, extraction factors affecting protein recovery were adjusted to determine the optimal conditions for each method. Alcalase provided the maximum protein recovery (30.04%), while less protein recovery was achieved with 0.1 N NaOH (55 °C), 1 N NaOH (55 °C), and Flavourzyme. Although the protein recovery achieved by 0.1 N NaOH (27.43%) was close to that of the Alcalase method, protein solubility by extraction with 0.1 N NaOH was much lower (23.46%) than that achieved via the enzymatic method (100%). Hence, the total soluble protein resulting from Alcalase extraction was higher than that obtained using either of the alkaline methods. Consequently, Alcalase extraction was determined to be the most effective method for extracting protein from CDR.


Analysis of break frequencies downstream of a constriction in a cylindrical tube.
Experiments were performed to correlate steady-flow power spectra downstream of a stenosis in a cylindrical tube with the flow geometry and velocity. The experiments were motivated by the need to improve quantitative phonoangiography. An objective break frequency (fb) was computed from spectra of velocity fluctuations, as measured with a hot film anemometer. Least squares fits with two independent variables were used to find an empirical relationship between a Strouhal number (S2), the contraction ratio (ds/D) and the Reynolds number (Re). The variables D and ds, are, respectively, the unobstructed tubing diameter and the inner diameter of the stenosis. The relationship found was S2 = Re 0.72(ds/D)0.26 The contraction ratio ds/D, can be found from the empirical relation in terms of known parameters. For the hot wire data the average error between the computed value of ds/D and the known value was 2.3%.


Biodegradation and extracellular enzymatic activities of Pseudomonas aeruginosa strain GF31 on β-cypermethrin.
Pseudomonas aeruginosa strain GF31, isolated from a contaminated soil, can effectively degrade β-cypermethrin (β-CP), as well as fenpropathrin, fenvalerate, and cyhalothrin. The highest level of degradation (81.2 %) was achieved with the addition of peptone. Surprisingly, the enzyme responsible for degradation was mainly localized to the extracellular areas of the bacteria, in contrast to the other known pyrethroid-degrading enzymes, which are intracellular. Although intact bacterial cells function at about 30 °C for biodegradation, similar to other degrading strains, the crude extracellular extract of strain GF31 remained biologically active at 60 °C. Moreover, the extract fraction showed good storage stability, maintaining >50 % of its initial activity following storage at 25 °C for at least 20 days. Significant differences in the characteristics of the crude GF31 extracellular extract compared with the known pyrethroid-degrading enzymes indicate the presence of a novel pyrethroid-degrading enzyme. Furthermore, the identification of 3-phenoxybenzoic acid and 2,2-dimethylcyclopropanecarboxylate from the degradation products suggests the possibility that β-CP degradation by both the strain and the crude extracellular fraction is achieved through a hydrolysis pathway. Further degradation of these two metabolites may lead to the development of an efficient method for the mineralization of these types of pollutants.


Mortality by road traffic injuries in Brazil (2000-2016): capital cities versus non-capital cities.
To compare the magnitude and trend of mortality by road traffic injuries (RTI) in the capitals and other municipalities of each Brazilian state between 2000 and 2016. A time series analysis of mortality rates by RTI standardized by age was performed, comparing the capitals and the cluster of non-capital municipalities in each state. Data on deaths were obtained from the Sistema de Informações sobre Mortalidade (SIM - Mortality Information System). RTI deaths were considered to be those, whose root cause was designated by ICD-10 codes V01 to V89, with redistribution of garbage codes. To estimate mortality rates, we used the population projections of the Brazilian Institute of Geography and Statistics (IBGE) from 2000 to 2015 and the population estimated by polynomial interpolation for 2016. The trend analysis was performed using the Prais-Winsten method, using the Stata 14.0 program. There were 601,760 deaths due to RTI in the period (114,483 of residents in capital cities). Mortality by RTI did not present an increasing trend in any of the Capitals in the period under study. Among non-capital municipalities, the trend was growing in 14 states. The greatest increase was observed in Piaui (AIR = 7.50%; 95%CI 5.50 - 9.60). There was a decreasing trend in RTI mortality in 14 capitals, among which Curitiba showed the greatest decrease (AIR = -4.82%; 95%CI -6.61 - -2.92). Only São Paulo and Rio Grande do Sul showed a decreasing trend in mortality by RTI in non-capital cities (AIR = 2.32%; 95%CI -3.32 - -1.3 and AIR = 1.2%, 95%CI -2.41 - 0.00, respectively). We conclude that RTI mortality rates in non-capital cities in Brazil showed alarming trends when compared with those observed in capital cities. The development of effective traffic safety actions is almost always limited to Brazilian capitals and large cities. Municipalities with higher risk should be prioritized to strengthen public policies for prevention and control.


Novel reverse genetics of genotype I and III Japanese encephalitis viruses assembled through transformation associated recombination in yeast: The reporter viruses expressing a green fluorescent protein for the antiviral screening assay.
Japanese encephalitis virus (JEV) belongs to a zoonotic flavivirus and is the main cause of viral encephalitis in humans throughout Asia. During the past two decades, both genotypes I (G) and III (GIII) JEVs co-existed in many Asian countries, and the prevalent strains have shifted from GIII to GI. Since all licensed JE vaccines are derived from GIII strains and no specific treatment is available, the development of novel vaccines and specific antiviral drugs against both genotypes is urgently required. To solve the unstable issue of the JEV infectious cDNA clone and establish a reliable antiviral screening assay, we established the yeast artificial chromosome (YAC)-based reverse genetics systems for GI and GIII JEV strains through transformation-associated recombination (TAR) technology in yeast. The YAC-based infectious clones of GI and GIII JEV exhibited high genetic stability both in yeast and E. coli. Using these reverse genetics systems, recombinant EGFP-reporter viruses were generated and remained stable for at least 10 passages in vitro. An image-based antiviral assay for JEV was developed with the EGFP-reporter viruses, and two drugs were identified to have a broad-spectrum inhibitory effect on GI and GIII JEV replication, which provide potential new therapeutic for the treatment of multiple genotypes JEV infection.


Associations between institutional-social-ecological factors and COVID -19 case-fatality: Evidence from 134 countries using multiscale geographically weighted regression (MGWR).
During the period in which the Omicron coronavirus variant was rapidly spreading, the impact of the institutional-social-ecological dimensions on the case-fatality rate was rarely afforded attention. By adopting the diagnostic social-ecological system (SES) framework, the present paper aims to identify the impact of institutional-social-ecological factors on the case-fatality rate of COVID-19 in 134 countries and regions and test their spatial heterogeneity. Using statistical data from the Our World In Data website, the present study collected the cumulative case-fatality rate from 9 November 2021 to 23 June 2022, along with 11 country-level institutional-social-ecological factors. By comparing the goodness of fit of the multiple linear regression model and the multiscale geographically weighted regression (MGWR) model, the study demonstrated that the effects of SES factors exhibit significant spatial heterogeneity in relation to the case-fatality rate of COVID-19. After substituting the data into the MGWR model, six SES factors were identified with an R square of 0.470 based on the ascending effect size: COVID-19 vaccination policy, age dependency ratio, press freedom, gross domestic product (GDP), COVID-19 testing policy, and population density. The GWR model was used to test and confirm the robustness of the research results. Based on the analysis results, it is suggested that the world needs to meet four conditions to restore normal economic activity in the wake of the COVID-19 pandemic: (i) Countries should increase their COVID-19 vaccination coverage and maximize COVID-19 testing expansion. (ii) Countries should increase public health facilities available to provide COVID-19 treatment and subsidize the medical costs of COVID-19 patients. (iii) Countries should strictly review COVID-19 news reports and actively publicize COVID-19 pandemic prevention knowledge to the public through a range of media. (iv) Countries should adopt an internationalist spirit of cooperation and help each other to navigate the COVID-19 pandemic. The study further tests the applicability of the SES framework to the field of COVID-19 prevention and control based on the existing research, offering novel policy insights to cope with the COVID-19 pandemic that coexists with long-term human production and life for a long time.


IR 820 dye encapsulated in polycaprolactone glycol chitosan: Poloxamer blend nanoparticles for photo immunotherapy for breast cancer.
In the present study, we have fabricated biocompatible and biodegradable monodisperse IR 820 encapsulated polycaprolactone (PCL) glycol chitosan (GC): Poloxamer blend nanoparticles (PP-IR NPs) for imaging and effective photo-immunotherapy. IR 820 has been used as an imaging and photothermal agent whereas glycol chitosan (GC) as an immunostimulatory agent. The combination of IR 820, poloxamer, and GC can be used effectively for photoimmunotherapy for cancer, drug-resistant and TNF-α resistant estrogen positive breast cancer. PP-IR NPs are stable in aqueous solution. The uniform size of 100-220 nm with a high zeta value of +38 ± 2 mV led them to accumulate in cancer cells. Laser treatment did not affect the morphology of PP-IR NPs as observed under the transmission electron microscope (TEM). In vitro cytotoxicity studies on MCF-7 cells showed enhanced toxicity upon laser treatment. Further, we validated the cell death by reactive oxygen species (ROS) production. Our studies thus showed that PP-IR NPs are effective in suppressing metastatic cancer as the combinational therapy leads to the formation of apoptotic bodies in MCF-7 cells.


The intensive care medicine clinical research agenda in paediatrics.
Intensive Care Medicine set us the task of outlining a global clinical research agenda for paediatric intensive care (PIC). In line with the clinical focus of this journal, we have limited this to research that may directly influence patient care. Clinician researchers from PIC research networks of varying degrees of formality from around the world were invited to answer two main questions: (1) What have been the major recent advances in paediatric critical care research? (2) What are the top 10 studies for the next 10 years? (1) Inclusive databases are well established in many countries. These registries allow detailed observational studies and feasibility testing of clinical trial protocols. Recent trials are larger and more valuable, and (2) most common interventions in PIC are not evidenced-based. Clinical studies for the next 10 years should address this deficit, including: ventilation techniques and interfaces; fluid, transfusion and feeding strategies; optimal targets for vital signs; multiple organ failure definitions, mechanisms and treatments; trauma, prevention and treatment; improving safety; comfort of the patient and their family; appropriate care in the face of medical complexity; defining post-PICU outcomes; and improving knowledge generation and adoption, with novel trial design and implementation strategies. The group specifically highlighted the need for research in resource-limited environments wherein mortality remains often tenfold higher than in well-resourced settings. Paediatric intensive care research has never been healthier, but many gaps in knowledge remain. We need to close these urgently. The impact of new knowledge will be greatest in resource-limited environments.


A Modified Polymeric Nano-formulation to Control Binding and Release of Insulin.
The study involves evaluation of the binding affinity of insulin to modified-hydrophobic nanoparticles to control its release. A specific peptide called hormone binding peptide (Hbpep) was designed to encompass most of the hydrophobic residues aiming to provide controlled hydrophobic interactions. Polycaprolactone (PCL) polymer was used here to prepare nanoparticles as carriers for insulin molecules. Hbpep ligand was attached covalently to these nanoparticles after embedding enormous carboxyl groups on the nanoparticles surface using conventional bioconjugation chemistry. The thermodynamic of insulin binding with the ligands was studied using isothermal titration calorimetry (ITC). The study further evaluated the adsorption behavior of insulin with the conjugates under various microenvironmental conditions using equilibrium microdialysis, fluorescence spectroscopy and dynamic light scattering. The adsorption process was found to be affected by changing the pH of the medium. The modified nanoparticles showed a controlled insulin binding especially at neutral pH. The energetics of binding was found to be of high affinity type demonstrating a potential for developing a controlled delivery system for insulin.


Developmental atlas of appendicularian Oikopleura dioica actins provides new insights into the evolution of the notochord and the cardio-paraxial muscle in chordates.
Locomotion by tail beating powered by a system of bilateral paraxial muscle and notochord is likely one of the key evolutionary innovations that facilitated the origin and radiation of chordates. The innovation of paraxial muscle was accompanied by gene duplications in stem chordates that gave rise to muscular actins from cytoplasmic ancestral forms, which acquired contractile capability thanks to the recruitment of the myosin motor-machinery. To better understand the role of actin diversification during the evolution of chordates, in this work we have characterized the complete actin catalogue of the appendicularian Oikopleura dioica, an urochordate that maintains a chordate body plan throughout its life, including the notochord in a muscled tail that confers an active free-living pelagic style. Our genomic survey, phylogenetic analyses and Diagnostic-Actin-Values (DAVs) reveal that O. dioica has four muscular actins (ActnM1-4) and three cytoplasmic actins (ActnC1-3), most of which originated by independent gene duplications during the evolution of the appendicularian lineage. Detailed developmental expression atlas of the complete actin catalogue of O. dioica reveals differences in the temporal-regulation and tissue-specificity of different actin paralogs, suggesting complex processes of subfunctionalization during the evolution of urochordates. Our results suggest the presence of a "cardio-paraxial" muscular actin at least in the last common ancestor of Olfactores (i.e. vertebrates+urochordates). Our results reveal highly dynamic tissue-specific expression patterns for some cytoplasmic actins, including the notochord, ciliated cells and neurons with axonal projections, which challenge the classic housekeeping notion ascribed to these genes. Considering that previous work had demonstrated the existence of notochord-specific actins in cephalochordates, the tissue-specific expression of two cytoplasmic actins in the notochord of O. dioica suggests that this pattern plausibly reflects the ancestral condition of chordates, and provides new insights to better understand the evolutionary origin of the notochord.


Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 5 from the dacA mutant strain of Escherichia coli (TMRL 1222).
The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Escherichia coli strain TMRL 1222 has been determined. The protein was purified to homogeneity and labeled with [14C] penicillin G. The labeled protein was digested with trypsin, and the active site tryptic peptide was purified by a combination of gel filtration and high-pressure liquid chromatography. Sequencing of the purified [14C]penicilloyl peptide yielded the sequence Arg-Asp-Pro-Ala-Ser-Leu-Thr-Lys, which corresponds to residues 40-47 of the gene sequence (Broome-Smith, J., Edelman, A., and Spratt, B. G. (1983) in The Target of Penicillin (Hakenbeck, R., Holtje, J.-V., and Labischinski, H., eds) pp. 403-408, Walter de Gruyter, Berlin). The catalytic amino acid residue that forms a covalent bond with penicillin was identified by treating the purified [14C]penicilloyl peptide with a mixture of proteases and then separating the radioactive products using high-pressure liquid chromatography. Analysis of the radioactive peaks by amino acid analysis confirmed that it is the serine residue that reacts with the beta-lactam ring of penicillin.


Internet-delivered psychological treatment as an add-on to treatment as usual for common mental disorders: A systematic review with meta-analysis of randomized trials.
Psychological treatments for common mental disorders are increasingly being delivered remotely via the internet. Evidence suggests that internet-delivered cognitive behavioural therapy (iCBT) is superior to waitlist. However, the benefits are unclear of using this treatment modality as an add-on to treatment as usual (TAU) in regular healthcare. The literature was systematically searched up to August 2021 for randomized trials of internet-delivered psychological treatments using TAU as the comparator. Eligible participants were diagnosed with depressive, anxiety, obsessive-compulsive, or trauma- and stress-related disorders. Outcomes of interest were symptoms, functioning, quality of life, healthcare utilization, and negative effects. Results were synthesized using random-effects meta-analyses. Quality of evidence was assessed using GRADE. The included studies evaluated iCBT for adults with depression (k = 9), depressive or anxiety disorders (k = 4), and post-traumatic stress disorder (k = 2) and were conducted in primary care or similar settings. For depression, low-certainty evidence suggested beneficial short-term effects on symptoms (g = -0.23; 95 % CI: = -0.37, -0.09), response rate (OR = 2.46; 1.31, 4.64), and remission (OR = 1.70; 1.19, 2.42;). The certainty of evidence was very low for long-term effects, other outcomes, and other disorders. TAU varied across studies and was often insufficiently described. iCBT as a complement to usual care for adult with depression may result in a small incremental effect, which potentially could be clinically important. Studies are lacking for several common disorders and for children, adolescents, and the elderly. More robust studies of long-term effects are also needed, to better inform clinical decision-making.


Relaxation by urocortin of human saphenous veins.
Urocortin, an endogenous peptide structurally related to corticotropin-releasing factor (CRF), has potent cardiovascular effects, suggesting that it may be of significance in cardiovascular regulation. The objective of this study was to analyse the effects of urocortin and its action mechanisms on human blood vessels. To this, 3 mm long segments from human saphenous veins were prepared for isometric tension recording in an organ bath. In the segments at basal resting tone, urocortin did not produce any effect, but in the segments precontracted with endothelin-1 (1 - 10 nM), urocortin (1 pM - 10 nM) produced concentration-dependent relaxation. This relaxation was not modified by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), but it was potentiated by the cyclo-oxygenase inhibitor meclofenamate (10 microM) and it was reduced by the inhibitors of high-conductance Ca2+-dependent potassium channels tetraethylammonium (TEA, 10 mM) and charybdotoxin (100 nM). These results indicate that human saphenous veins are very sensitive to urocortin, which produces vascular relaxation by a mechanism independent of nitric oxide and dependent of high-conductance Ca2+-dependent potassium channels, and that it may be opposed by the release of vasoconstrictor prostanoids. Therefore, urocortin may be of significance for regulation of the venous circulation in humans.


Effect of rimonabant, micronised fenofibrate and their combination on cardiometabolic risk factors in overweight/obese patients: a pilot study.
To assess the effect of rimonabant, micronised fenofibrate and their combination on anthropometric and metabolic parameters in overweight/obese patients with dyslipidaemia. All patients (n = 30) received a hypocaloric diet ( approximately 600 kcal/day deficit) and were randomly allocated to receive open-label rimonabant (R) 20 mg/day (n = 10), micronised fenofibrate (F) 200 mg/day (n = 10) or rimonabant 20 mg/day plus fenofibrate 200 mg/day (RF) (n = 10). Anthropometric and metabolic parameters were assessed at baseline and 3 months after treatment initiation. Compared with baseline similar significant reductions in body weight, body mass index and waist circumference were observed in the R (-6, -5 and -5%, respectively; p < 0.01) and RF group (-5% for all, p < 0.05), while improvements in these parameters were smaller in the F group (-2, -2.5 and -2%, respectively; p < 0.05). Triglycerides were reduced by 18% in the R group (p = NS), by 39% in the F group (p < 0.001) and by 46% in the RF group (p < 0.05). Importantly, combination treatment resulted in a 42% increase in high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05), while HDL-C was not significantly altered in the two monotherapy groups. Subsequently, a more pronounced increase in apolipoprotein A-I (ApoA-I) levels (+25%) was observed in the RF group compared with changes in both monotherapy groups (p < 0.0001 vs R and p < 0.005 vs F group). Low-density lipoprotein cholesterol (LDL-C) levels were not significantly altered in any group. Apolipoprotein B (apoB) levels were reduced in all groups and this reduction was significantly more pronounced in the RF group (p < 0.05 vs baseline as well as p < 0.005 and p < 0.01 for RF vs R and F groups, respectively). ApoB/apoA-I ratio decreased by 3% with R (p = NS), by 18% with F (p < 0.05) and by 40% with RF treatment (p < 0.01). Total cholesterol to HDL-C ratio decreased by 20% with F (p < 0.0001) and by 33% with RF therapy (p < 0.005), while it was not significantly altered in R group. The combination of rimonabant and fenofibrate may further improve metabolic parameters in overweight/obese patients with dyslipidaemia compared with each monotherapy. This improvement is particularly pronounced for HDL-C levels.


Radionuclide measurement of bladder emptying rate. Simultaneous comparison with urinary flow rate obtained by uroflowmetry.
Mean and peak bladder emptying rates were measured by a radionuclide method using a gamma camera and Tc-99m DTPA and were compared with average and maximum urinary flow rates obtained by a uroflowmeter in 24 simultaneous measurements. A good correlation was found between the two methods. Average urinary flow rate correlates better with mean bladder emptying rate (r = 0.96, y = 1.04X + 0.14, s.e.e. = 1.2) than maximum urinary flow rate with peak bladder emptying rate (r = 0.83, y = 0.78X + 4.5, s.e.e. = 4.2). The results suggest that the radionuclide method can be used to measure the urinary flow rate, and has the advantage of establishing the postvoid residual urine.


Does 'Strong Analgesic' Equal 'Strong Opioid'? Tapentadol and the Concept of 'µ-Load'.
The distinct properties of the centrally-acting analgesic tapentadol derive from the combined contributions of an opioid component and a nonopioid component. However, the opioid component's relative contribution to analgesic and adverse effects has not previously been elucidated. Tapentadol's analgesic effect derives from the combined contribution of an opioid mechanism and a nonopioid mechanism, the extent of which can vary for different pains. Likewise, the interaction can vary for various adverse effects. Hence, the contribution of each mechanism to adverse effects can be different from the contribution to analgesia. We here estimate the percent contribution of each component of the mechanism of action to analgesia and to adverse effects. Several approaches to in vitro and in vivo data to estimate the contribution of tapentadol's opioid component to analgesia and to the two important opioid adverse effects, respiratory depression and constipation. The results are then compared with clinical data. Traditional opioids, such as morphine, oxycodone, and others, produce their analgesic effects primarily through a single mechanism-the activation of µ-opioid receptors (MOR). Therefore, the contribution of the opioid component to adverse effects is 100%. In contrast, the newer strong analgesic tapentadol produces its analgesic effect via two separate and complementary analgesic mechanisms, only one of which is µ-opioid. We applied standard drug-receptor theory and novel techniques to in vitro and in vivo data to estimate by several different ways the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and we compared the results to clinical evidence. The estimate is remarkably consistent over the various approaches and indicates that the μ-load of tapentadol is ≤ 40% (relative to pure MOR agonists, which have, by definition, a µ-load of 100%). Grünenthal GmbH.


Determinants of vaccine refusal, delay and reluctance in parents of 2-year-old children in Canada: Findings from the 2017 Childhood National Immunization Coverage Survey (cNICS).
Vaccine hesitancy is a barrier to improving childhood vaccination rates in Canada, but the scope of this problem is unclear due to inconsistent measurement of vaccine uptake indicators. Using 2017 data from a Canadian national vaccine coverage survey, this study analyzed the impact of demographics and parental knowledge, attitudes and beliefs (KAB) on vaccine decisions (refusal, delay and reluctance) in parents of 2-year-old children who had received at least one vaccine. The findings show that 16.8% had refused a vaccine, specifically influenza (73%), rotavirus (13%) and varicella (9%); female parents or those from Quebec or the Territories more likely to refuse. 12.8% were reluctant to accept a vaccine, usually influenza (34%), MMR (21%) and varicella (19%), but eventually accepted them upon advice from a health care provider. 13.1% had delayed a vaccine, usually because their child had health issues (54%) or was too young (18.6%) and was predicted by five or six person households. Recent immigration to Canada decreased likelihood of refusal, delay, or reluctance; however, after 10 years in Canada, these parents were as likely to refuse or be reluctant as parents born in Canada. Poor KAB increased likelihood of refusal and delay by 5 times, and reluctance by 15 times, while moderate KAB increased likelihood of refusal (OR 1.6), delay (OR 2.3) and reluctance (OR 3.6). Future research into vaccine decisions by female and/or single parents, and predictors of vaccine KAB would provide valuable information and help protect our children from vaccine preventable diseases.


A differential impact of mycophenolic acid, prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.
Soluble CD30 (sCD30) has been associated with rejection and graft loss in kidney transplantation, leading to the suggestion that sCD30 might be a useful biomarker to adjust immunosuppressant medication dosing. However, there has been minimal study of the influence of individual immunosuppressive drugs on sCD30 levels. To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients. The sCD30 levels were measured pretransplant and 30 days posttransplant. Area under the concentration-time curve (AUC) for each drug was estimated on day 30 using validated, multiple regression-derived limited sampling strategies. One hundred twenty-five subjects were included. Median (interquartile range) sCD30 levels were lower on day 30 posttransplant compared with pretransplant [10.7 (3.7-20.1) pg/mL versus 66.5 (46.0-95.1) pg/mL; P < 0.0001]. On univariate analyses, day 30 sCD30 levels were negatively correlated with MPA exposure and positively correlated with tacrolimus exposure. Using multivariate logistic regression, higher tacrolimus exposure was independently associated with higher day 30 sCD30 levels (2.2 change in odds for an SD increase in tacrolimus AUC 0-12, P = 0.01; 5.5 change in odds for an SD increase in tacrolimus predose concentration, P < 0.0001). In contrast, MPA and total and free prednisolone exposures were not independently associated with sCD30 levels. The sCD30 levels are significantly reduced in the presence of combination immunosuppression but are differentially affected by different immunosuppressant agents. More research is required before introduction of sCD30 measurement into clinical practice can be considered.


Reductive debromination of 1,2-dibromides with anisidines.
vic -Dibromides containing the α-bromocarbonyl or α-bromoaromatic moieties were reductively debrominated to furnish alkenes in high yield. o- and m-Anisidines but not p-anisidine were found to be effective debrominating agents. The reductive debrominations were found to be trans-stereospecific.


Organophosphate insecticides disturb neuronal network development and function via non-AChE mediated mechanisms.
Exposure to organophosphate (OP) insecticides has been related to several adverse health effects, including neurotoxicity. The primary insecticidal mode of action of OP insecticides relies on (irreversible) binding to acetylcholine esterase (AChE), with -oxon metabolites having a much higher potency for AChE inhibition than the parent compounds. However, OP insecticides can also have non-AChE-mediated effects, including changes in gene expression, neuroendocrine effects, disruption of neurite outgrowth and disturbance of the intracellular calcium (Ca2+) homeostasis. Since Ca2+ is involved in neurotransmission and neuronal development, our research aimed to assess the effects of two widely used OP insecticides, chlorpyrifos (CPF) and diazinon (DZ) and their respective -oxon metabolites, on intracellular Ca2+ homeostasis in human SH-SY5Y cells and rat primary cortical cultures. Furthermore, we assessed the acute and chronic effects of exposure to these compounds on neuronal network maturation and function in rat primary cortical cultures using microelectrode array (MEA) recordings. While inhibition of AChE appears to be the primary mode of action of oxon-metabolites, our data indicate that both parent OP insecticides (CPF and DZ) inhibit depolarization-evoked Ca2+ influx and neuronal activity at concentrations far below their sensitivity for AChE inhibition, indicating that inhibition of voltage-gated calcium channels is a common mode of action of OP insecticides. Notably, parent compounds were more potent than their oxon metabolites, with exposure to diazinon-oxon (DZO) having no effect on both neuronal activity and Ca2+ influx. Human SH-SY5Y cells were more sensitive to OP-induced inhibition of depolarization-evoked Ca2+ influx than rat cortical cells. Acute exposure to OP insecticides had more potent effects on neuronal activity than on Ca2+ influx, suggesting that neuronal activity parameters are especially sensitive to OP exposure. Interestingly, the effects of DZ and chlorpyrifos-oxon (CPO) on neuronal activity lessened after 48 h of exposure, while the potency of CPF did not differ over time. This suggests that neurotoxicity after exposure to different OPs has different effects over time and occurs at levels that are close to human exposure levels. In line with these results, chronic exposure to CPF during 10 days impaired neuronal network development, illustrating the need to investigate possible links between early-life OP exposure and neurodevelopmental disorders in children and highlighting the importance of non-AChE mediated mechanisms of neurotoxicity after OP exposure.


Novel endovascular treatment of enlarging facial artery pseudoaneurysm resulting from molar extraction: a case report.
A novel endovascular therapy to treat a pseudoaneurysm as a complication of molar tooth extraction is described. A 20-year-old man presented 2 weeks after third molar tooth extraction with an enlarging pulsatile jaw mass, identified as a facial artery pseudoaneurysm. Endovascular embolization with microcoils and a liquid embolic agent, Onyx, was performed. The use of Onyx in this manner is an off-label use. Immediately after treatment, the pulsatile mass resolved and remained obliterated at 2 months of follow-up. Onyx embolization of facial artery vascular lesions can be safely accomplished while avoiding microvascular complications and provides a satisfactory and durable result.


Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia.
The combination of cytotoxic treatment with strategies for immune activation represents an attractive strategy for tumour therapy. Following reduction of high tumour burden by effective cytotoxic agents, two major immune-stimulating approaches are being pursued. First, innate immunity can be activated by monoclonal antibodies triggering antibody-dependent cellular cytotoxicity. Second, tumour-specific T cell responses can be generated by immunization of patients with peptides derived from tumour antigens and infused in soluble form or loaded onto dendritic cells. The choice of cytotoxic agents for such combinatory regimens is crucial since most substances such as fludarabine are considered immunosuppressive while others such as cyclophosphamide can have immunostimulatory activity. We tested in this study whether fludarabine and/or cyclophosphamide, which represent a very effective treatment regimen for chronic lymphocytic leukaemia, would interfere with a therapeutic strategy of T cell activation. Analysis of peripheral blood samples from patients prior and during fludarabine/cyclophosphamide therapy revealed rapid and sustained reduction of tumour cells but also of CD4(+) and CD8(+) T cells. This correlated with a significant cytotoxic activity of fludarabine/cyclophosphamide on T cells in vitro. Unexpectedly, T cells surviving fludarabine/cyclophosphamide treatment in vitro had a more mature phenotype, while fludarabine-treated T cells were significantly more responsive to mitogenic stimulation than their untreated counterparts and showed a shift towards T(H)1 cytokine secretion. In conclusion, fludarabine/cyclophosphamide therapy though inducing significant and relevant T cell depletion seems to generate a micromilieu suitable for subsequent T cell activation.


[Health simulation in initial training, a reality to be increased].
Simulated practice is a pedagogical tool that invites students to immerse themselves in scenarios close to reality. It confronts them with experiential learning while giving them the opportunity to explore and deconstruct what they have experienced in a distanced and group-based manner during debriefings. Simulation is a recognized tool for continuing professional development, but it is difficult for it to become established in the context of initial training. Its implementation requires certain human and financial resources.


Methotrexate-conjugated chitosan-grafted pH- and thermo-responsive magnetic nanoparticles for targeted therapy of ovarian cancer.
Here, methotrexate (MTX)-conjugated multifunctional nanoparticles (NPs) were engineered based on chitosan (CS) for targeted delivery of erlotinib (ETB). First, CS was modified with sodium dodecyl sulfate and maleic anhydride to prepare a polymerizable organo-soluble precursor. N-Isopropylacrylamide (NIPAAm) and itaconic acid (IA) as thermo- and pH-responsive monomers were grafted onto CS by free radical polymerization. Subsequently, magnetic nanoparticles (MNPs) ferrofluid with prepared CS copolymer (CSC) was produced via an inclusion complex between carboxylic acid groups of CSC and MNPs. Finally, MTX was conjugated to amino groups of CS based on the structural similarity of MTX with folic acid as targeting ligand. The prepared MTX-CSC@MNPs were physiochemically characterized by different techniques, including FT-IR, 1H NMR, DLS, SEM-EDX, and UV-Vis spectroscopy. The mean size of the prepared NPs was around 112 nm with a zeta potential of -28.4 mV. The ETB encapsulation efficiency and NPs loading were about 86% and 17%, respectively. The ETB-loaded NPs showed thermo- and pH-dependent drug release behavior. The ETB-loaded MTX-CSC@MNPs were markedly taken up via folate receptors (FRs) and induced significant toxicity in OVCAR-3 cells. Based on these findings, MTX-CSC@MNPs are proposed as a promising smart nanocarrier for the targeted therapy of FR-positive solid tumors such as ovarian cancer.


Changing Urban-Rural Disparities in the Utilization of Direct-Acting Antiviral Agents for Hepatitis C in U.S. Medicare Patients, 2014-2017.
The advent of direct-acting antiviral agents for treating hepatitis C virus infection has made hepatitis C virus elimination possible. Rural patients with hepatitis C virus infection may be less likely to access direct-acting antiviral agents, but the real-world evidence is scarce on urban-rural disparities in direct-acting antiviral agent utilization. This retrospective cohort study was conducted in 2019-2020 using Medicare data to examine urban-rural disparities in direct-acting antiviral agent utilization among newly diagnosed patients with hepatitis C virus infection in 2014-2016. Direct-acting antiviral agent use was defined as filling ≥1 prescription for direct-acting antiviral agents during 2014-2017, and patient's urban-rural status was classified on the basis of their ZIP code of residence. This study evaluated the associations between multilevel factors and direct-acting antiviral agent use with a focus on urban-rural disparities. It also assessed changes over time in urban-rural disparities in direct-acting antiviral agent utilization using multivariable cause-specific Cox regression analyses with time-varying hazard ratios. Among 204,018 new patients with hepatitis C virus infection, about 30% received direct-acting antiviral agents during 2014-2017. Cumulative direct-acting antiviral agent use gradually increased over time in both urban and rural patients. However, the increase was greater in urban patients than in rural patients. In the first year of follow-up, rural patients had a similar rate of receiving direct-acting antiviral agents (adjusted hazard ratio=1.03, 95% CI=1.00, 1.07), but they were less likely to use direct-acting antiviral agents in later years than urban patients (adjusted hazard ratio=0.85, 95% CI=0.81, 0.90 in the second year, adjusted hazard ratio=0.82, 95% CI=0.76, 0.89 in the third year, and adjusted hazard ratio=0.76, 95% CI=0.64, 0.90 in the fourth year of follow-up). This study reveals important gaps in hepatitis C virus treatment and suggests increasing urban-rural disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection.


A Risk Model and Cost Analysis of Incisional Hernia After Elective, Abdominal Surgery Based Upon 12,373 Cases: The Case for Targeted Prophylactic Intervention.
Incisional hernia (IH) remains a common, highly morbid, and costly complication. Modest progress has been realized in surgical technique and mesh technology; however, few advances have been achieved toward understanding risk and prevention. In light of the increasing emphasis on prevention in today's health care environment and the billions in costs for surgically treated IH, greater focus on predictive risk models is needed. All patients undergoing gastrointestinal or gynecologic procedures from January 1, 2005 to June 1, 2013, within the University of Pennsylvania Health System were identified. Comorbidities and operative characteristics were assessed. The primary outcome was surgically treated IH after index procedures. Patients with prior hernia, less than 1-year follow-up, or emergency surgical procedures were excluded. Cox hazard regression modeling with bootstrapped validation, risk factor stratification, and assessment of model performance were conducted. A total of 12,373 patients with a 3.5% incidence of surgically treated IH (follow-up 32.2 ± 26.6 months) were identified. The cost of surgical treatment of IH and management of associated complications exceeded $17.5 million. Notable independent risk factors for IH were ostomy reversal (HR = 2.76), recent chemotherapy (HR = 2.04), bariatric surgery (HR = 1.78), smoking history (HR = 1.74), liver disease (HR = 1.60), and obesity (HR = 1.96). High-risk patients (20.6%) developed IH compared with 0.5% of low-risk patients (C-statistic = 0.78). This study demonstrates an internally validated preoperative risk model of surgically treated IH after 12,000 elective, intra-abdominal procedures to provide more individualized risk counseling and to better inform evidence-based algorithms for the role of prophylactic mesh.


Comparison of serum concentrations of ceftazidime and tobramycin in newborn infants.
Peak and trough serum concentrations of ceftazidime and tobramycin were determined in neonates with suspected septicaemia in an open randomized study. Mean peak serum levels were 85 (+/- 4.4 SE) mg/l for ceftazidime and 5.8 (+/- 0.3 SE) mg/l for tobramycin. The peak serum levels of ceftazidime were well above the reported minimal inhibitory concentration (MIC)90 values of pathogenic bacteria encountered in neonates, while peak serum levels of tobramycin were lower than reported MIC90 values for Klebsiella, Pseudomonas, Enterobacter and Serratia species. Nine of 33 tobramycin-treated patients had potentially toxic trough serum levels (greater than 2 mg/l) and nine had subtherapeutic peak serum levels (less than 4 mg/l). The dosage of this antibiotic had to be changed frequently. In comparison only 2 of 29 ceftazidime-treated patients had subtherapeutic peak levels (less than 40 mg/l) and none had potentially toxic trough levels (greater than 40 mg/l). Ceftazidime, in comparison with tobramycin, has a more favourable antibacterial spectrum and routine determinations of peak and trough serum levels should not be necessary.


Use of 3D imaging in CT of the acute trauma patient: impact of a PACS-based software package.
To evaluate the impact of a picture archiving and communication systems (PACS)-based software package on the requests for 3D reconstructions of multidetector CT (MDCT) data sets in the emergency radiology of a level 1 trauma center, we reviewed the number and type of physician requests for 3D reconstructions of MDCT data sets for patients admitted after sustaining multiple trauma, during a 12-month period (January 2003-December 2003). During the first 5 months of the study, 3D reconstructions were performed in dedicated workstations located separately from the emergency radiology CT interpretation area. During the last 7 months of the study, reconstructions were performed online by the attending radiologist or resident on duty, using a software package directly incorporated into the PACS workstations. The mean monthly number of 3D reconstructions requested during the two time periods was compared using Student's t test. The monthly mean +/- SD of 3D reconstructions performed before and after 3D software incorporation into the PACS was 34+/-7 (95% CI, 10-58) and 132+/-31 (95% CI, 111-153), respectively. This difference was statistically significant (p<0.0001). In the multiple trauma patient, implementation of PACS-integrated software increases utilization of 3D reconstructions of MDCT data sets.


Ulcerative colitis with relative sparing of the rectum. Clinical features, histology, and prognosis.
A series of 12 patients with relative sparing of the rectum in ulcerative colitis is analyzed. Half were recorded as having normal sigmoidoscopic appearance and, in every case, double-contrast barium enema showed an apparently normal rectum but an abnormal colon. Rectal biopsy showed changes compatible with ulcerative colitis in all cases, though in four, changes were slight. Thus, complete histologic sparing of the rectum was not observed. In four of six patients treated by colectomy and ileorectal anastomosis, inflammation of the retained rectum required medical or surgical treatment.


Cyber victimization by peers: Prospective associations with adolescent social anxiety and depressive symptoms.
Peer victimization that occurs via electronic media, also termed cybervictimization, is a growing area of concern for adolescents. The current study evaluated the short-term prospective relationship between cybervictimization and adolescents' symptoms of social anxiety and depression over a six-week period. Participants were 839 high-school aged adolescents (14-18 years; 58% female; 73% Hispanic White), who completed measures of traditional peer victimization, cybervictimization, depression, and social anxiety at two time points. Findings supported the distinctiveness of cybervictimization as a unique form of peer victimization. Furthermore, only cybervictimization was associated with increased levels of depressive symptoms over time, and only relational victimization was associated with increased social anxiety over time, after controlling for the comorbidity of social anxiety and depression among youth. Cybervictimization appears to be a unique form of victimization that contributes to adolescents' depressive symptoms and may be important to target in clinical and preventive interventions for adolescent depression.


Complexes of N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid with group 12 metals and vanadium-Synthesis, structure and bioactivity of the vanadium complex.
Four new complexes of group 12 metals [Zn(II), Cd(II) and Hg(II)], along with vanadyl bound to the ligand N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid, have been synthesized and characterized. The structure of the complexes with Zn(II), Hg(II) and V(IV) was determined by X-ray structural analysis. In all observed cases, the symmetry of these complexes was found to be distorted octahedral. The inhibition of protein tyrosine phosphatase 1B by the vanadium(IV) complex was demonstrated. The cytotoxicity of the vanadium(IV) complex was tested in vitro against three cancer cell lines, with a comparison of the activity of the free ligand and of vanadyl acetylacetonate and sodium orthovanadate. The IC50 values of the complex were in the range of 9 to 21μM. Remarkably, cytotoxic potency in the multidrug-resistant non-small cell lung cancer cell line A549 was at least as high as in the broadly chemosensitive ovarian teratocarcinoma cell line CH1(PA-1).


Latina Mothers' Cultural Experiences, Beliefs, and Attitudes May Influence Children's Math Learning.
Drawing from a qualitative approach and through individual pláticas (processes of co-constructing knowledge through dialogue) as a linguistic and cultural framework, this work explored informal contextual factors valued by Spanish-speaking Latina mothers of children, three to five years of age and enrolled in a nonprofit California preschool. Results revealed that Latina mothers have cultural forms of knowledge which impact their children's educational experiences and engage in direct and indirect numeracy environments. While personal math experiences and home practices differed, Latina mothers experience and navigate their children's learning based on sociocultural aspects, influencing how they support their children's math learning. This study drew from sociocultural learning theories that value learning embedded within meaningful learning experiences. Patterns of family learning have several implications for educational practice, especially for Latine families whose parent participation is typically not as visible as White American English-speaking parents.


Dental injuries in pediatric patients with facial fractures are frequent and severe.
This study was carried out to identify the occurrence, type, location, and severity of dental injuries (DIs), as well as predictors for DIs, in pediatric patients with facial fractures. This study examined the files of patients aged 16 years or less who had sustained facial fractures during a 12-year period. The outcome variable was DI. The explanatory variables included gender, age, trauma mechanism, and type of facial fracture. Data analysis was carried out with the χ(2) test and logistic regression analysis. A total of 200 patients, 119 (59.5%) of whom were boys, met the inclusion criteria. The mean age was 12.6 years. A total of 45 patients (22.5%) had DIs. Crown fracture, the most common type of DI, occurred in 59.9% of all DIs. The most common location of crown fractures was in the premolars (37.4% of all crown fractures). Multiple DIs occurred in 71.1% of those with DIs and severe DI in 66.7%. DIs were significantly associated with motor vehicle collision (MVC) (P = .02) and mandibular fracture (P = .03). DIs are common in pediatric patients with facial fracture, often being both multiple and severe. In association with pediatric facial fracture, facial surgeons should be especially alert for crown fractures in the lateral parts of the jaws.


Dual approach for large mediastinal tumors in the thoracic outlet: transmanubrial osteomuscular sparing approach and video-assisted thoracoscopic surgery.
Selecting the proper surgical approach for mediastinal tumors in the thoracic outlet is difficult. Video-assisted thoracoscopic surgery is ideal because of the less invasiveness; however, it is often difficult to resect tumors only by video-assisted thoracoscopic surgery due to the poor visualization of the cranial side of tumors. We report two successfully treated cases by using a dual approach consisting of the transmanubrial osteomuscular sparing technique and video-assisted thoracoscopic surgery for aiming both the less invasiveness and the good visualization of the cranial side of tumors. We present two resected cases of the mediastinal tumor in the thoracic outlet. The first case was a 28-year-old woman and the second case was a 37-year-old man. They had a mediastinal tumor in the thoracic outlet which was detected on the roentgenogram. A definitive preoperative diagnosis was unavailable. The surgical resection was started with video-assisted thoracoscopic surgery in the both cases. After the dissection of the caudal side of the tumor, the dissection of the cranial side was judged to be difficult and risky because the tumor was located adjacent to major vessels and the good visualization of this side couldn't be acquired. Therefore, the transmanubrial approach was sequentially performed and complete resection was safely achieved. Postoperatively, although transient Horner syndrome appeared in both cases, they recovered from this syndrome and were discharged. The final diagnosis was schwannoma for both cases. Neither of the cases had any functional restriction of the upper extremity. This dual approach for mediastinal tumors in the thoracic outlet is useful in terms of safety and lower invasiveness.


Effects of phosphorylation, MgATP, and ionic strength on the rates of papain degradation of heavy and light chains of smooth muscle heavy meromyosin at the S1-S2 junction.
The effects of ionic strength, MgATP, and phosphorylation on the degradation rates of heavy meromyosin (HMM) by papain have been compared to their effects on the sedimentation coefficient (s20,w) to determine the relationship of the degradation rate to the equilibrium between the flexed and the extended forms (Suzuki, H., Stafford, W. F., Slayter, H. S., and Seidel, J. C. (1985) J. Biol. Chem. 260, 14810-14817). At 0.025 M NaCl, where HMM is predominantly in the flexed form, MgATP, Mg-adenylyl imidodiphosphate or MgADP reduce kH by 80-90%. MgATP exerts its optimal effect at this ionic strength, where at least 70% of HMM is flexed in the presence or absence of MgATP, suggesting that nucleotides reduce kH by decreasing the proteolytic susceptibility of the flexed form. At 0.5 M NaCl, where HMM is in the extended form, MgATP has no effect on kH. At low ionic strengths phosphorylation decreases kH but increases it in the presence of MgATP. Plots of kH against s20,w determined at various ionic strengths are linear, the data for phosphorylated and dephosphorylated HMM falling on the same line. Thus, raising the ionic strength or phosphorylating the 20-kDa light chain appears to alter kH by increasing the fraction of HMM in the extended form. The degradation rate of the 20-kDa light chain (kL) of dephosphorylated HMM responds to changes in ionic strength in essentially the same way as does kH, suggesting that the response of kL to changes in ionic strength can also be attributed to conversion of HMM to the extended form. However, kL for phosphorylated HMM measured in the presence of MgATP exhibits very little dependence on ionic strength.


Hospitalizations at the End of Life Among Chronic Obstructive Pulmonary Disease and Lung Cancer Patients: A Nationwide Study.
Patients with chronic obstructive pulmonary disease (COPD) and lung cancer report several symptoms at the end of life and may share palliative care needs. However, these disease groups have distinct health care use. To compare the frequency and length of hospitalizations during the last month of life between patients with COPD and lung cancer, assessing the main characteristics associated with these outcomes. Data were retrieved from the Portuguese Hospital Morbidity Database. Deceased patients in a public hospital from mainland Portugal (2010-2015), with COPD as the main diagnosis of the last hospitalization (n = 2942) were sex and age matched (1:1) with patients with lung cancer. The association of patients' main diagnosis, and individual, hospital and area of residence characteristics, on frequency (>1) and length (>14 days) of end-of-life hospitalizations were quantified through adjusted odds ratio (OR) and respective 95% confidence intervals (CIs). Hospitalizations for >14 days during the last month of life were more likely for lung cancer patients than COPD patients (OR = 1.12; 95% CI = 1.00-1.25). Among patients with COPD, male sex (OR = 1.50; 95% CI = 1.25-1.80) and death in a large hospital (OR = 1.82; 95% CI = 1.41-2.35) were positively associated with longer hospitalizations; the occurrence of >1 hospitalization and hospitalizations for >14 days were less likely among those from rural areas (OR = 0.72, 95% CI = 0.55-0.94; OR = 0.67, 95% CI = 0.54-0.83, respectively). In patients with lung cancer, male sex was negatively associated with longer hospitalizations (OR = 0.82; 95% CI = 0.69-0.98). At the end of life, patients with lung cancer had longer hospitalizations than patients with COPD, and the main characteristics associated with the frequency and length of hospitalizations differed according to the patients' main diagnosis.


Alternative promoter usage generates multiple evolutionarily conserved isoforms of Drosophila DOA kinase.
The unique LAMMER (or Clk) protein kinase of Drosophila is encoded at the Doa locus. To better understand the pleiotropic effects of Doa mutations, we describe the structure and expression of the multiple RNA and protein products of the locus, as well as their evolutionary conservation among Drosophila. The gene produces at least six different protein isoforms, primarily through alternative promoter usage, generating kinases with virtually identical catalytic domains but variable N-terminal noncatalytic domains. The single known alternative splicing event generates a kinase with the insertion of six additional amino-acids in the catalytic domain. Two independent predicted genes nested within Doa introns actually encode additional alternative N-termini of the locus. An alternative polyadenylation site utilized exclusively during early embryogenesis generates a transcript with a short half-life, apparently to ensure a "burst" of kinase expression at the onset of development. Ecdysone induction of Doa transcripts affects all isoforms during pupariation. Finally, extensive conservation of amino-acid sequences of both the catalytic and N-terminal noncatalytic exons observed in alignments between D. melanogaster exons and the genome sequences of 11 other Drosophila species suggest that the multiple isoforms serve important and nonredundant functions.