Customer focus level following implementation of quality improvement model in Tehran social security hospitals.
The key factor for the success of total quality management programs in an organization is focusing on the customer. The purpose of this paper is to assess customer focus level following implementation of a quality improvement model in social security hospitals in Tehran Province. This research was descriptive-comparative in nature. The study population consisted of the implementers of quality improvement model in four Tehran social security hospitals. The data were gathered through a checklist addressing customer knowledge and customer satisfaction. The research findings indicated that the average scores on customer knowledge in Shahriar, Alborz, Milad, and Varamin hospitals were 64.1, 61.2, 54.1, and 46.6, respectively. The average scores on customer satisfaction in Shahriar, Alborz, Milad, and Varamin hospitals were 67.7, 65, 59.4, and 50, respectively. The customer focus average scores in Shahriar, Alborz, Milad, and Varamin hospitals were 66.3, 63.3, 57.3, and 48.6, respectively. The total average scores on customer knowledge, satisfaction and customer focus in the investigated hospitals proved to be 56.4, 60.5, and 58.9, respectively. The paper is of value in showing that implementation of the quality improvement model could considerably improve customer focus level.


Hydrothermal preparation of BaSnO3 and Au-BaSnO3 nanorods.
Barium stannate nanorods have been synthesized using chloride precursors, which were activated to form composite complexes and subjected to hydrothermal treatment in a teflon lined reactor. The reaction time was varied between 0.5 to 6.0 h. The reaction conditions included alkaline pH, pressure of 75 kg/cm2 and temperature below 200 degrees C. The sample powders were further calcined at 200, 400 and 600 degrees C for 4 h each. The phase formation was confirmed by IR and XRD. The cubic phase of BaSnO3 powder obtained at 600 degrees C was observed under electron microscope and revealed the formation of long rods of length 2-5 microm with a diameter of 50-60 nm. The use of TMAOH as a mineralizer resulted in the formation of shorter and finer nanofibres. The nanorods were sonicated in presence of auric chloride solution in alkaline medium and the formation of Au-BaSnO3 composite powder was confirmed by UV-visible spectroscopy and X-ray diffraction technique.


A computational method for selecting short peptide sequences for inorganic material binding.
Discovering or designing biofunctionalized materials with improved quality highly depends on the ability to manipulate and control the peptide-inorganic interaction. Various peptides can be used as assemblers, synthesizers, and linkers in the material syntheses. In another context, specific and selective material-binding peptides can be used as recognition blocks in mining applications. In this study, we propose a new in silico method to select short 4-mer peptides with high affinity and selectivity for a given target material. This method is illustrated with the calcite (104) surface as an example, which has been experimentally validated. A calcite binding peptide can play an important role in our understanding of biomineralization. A practical aspect of calcite is a need for it to be selectively depressed in mining sites.


High-risk sexual behaviours and genital chlamydial infections in high school students in Southern Taiwan.
The objective of this study was to determine the prevalence of high-risk sexual behaviours and sexually transmitted infections (STIs) and associated risk factors in Taiwanese high school students. Students in grades 10 and 11 (mean age: 15.9 +/- 0.9; range: 13-20 years) at two schools were recruited. An anonymous online real-time computer-assisted self-interviewing questionnaire was designed to assess demographic factors and sexual behaviours. Urine specimens were tested for genital chlamydial and gonococcal infections. The same survey and screening was conducted one year later on the same group of students. Overall, 670 individual students (993 visits) were enrolled with 323 students in both surveys. Twenty-seven percent had had sexual intercourse, and more than three quarters (79%) of them had engaged in high-risk sexual behaviours. Having friends using drugs increased the odds of practicing high-risk sexual behaviours (odds ratio [OR] 1.99, 95% CI: 1.13 to 3.50). Among 182 sexually active students, 8.8% had chlamydial (female: 12.5%; male: 5.3%) and 1.1% had gonococcal infections. Having sex with someone met on the Internet was the most significant risk factor for acquiring chlamydia (OR 8.14, 95% CI: 2.82 to 23.51). In conclusion, this adolescent population reported high prevalence of high-risk sexual behaviours and had a high prevalence of chlamydia supportive of a potential epidemic of STIs and HIV.


Decreased light intensity alters the perception of day length by male European starlings (Sturnus vulgaris).
The breeding season of wild starlings is controlled by photoperiod. Full breeding condition is attained during exposure to lengthening days in the spring, and photorefractoriness ensues. The reproductive system of starlings will not subsequently be stimulated by long day lengths until photorefractoriness is dissipated by the short day lengths experienced in the autumn and winter. Unlike most studies on avian photoperiodism, this investigation involved manipulation of light intensity of a fixed photoperiod rather than of photoperiod itself. Photosensitive starlings transferred from short days to long days of different light intensities underwent graded reproductive responses according to the light intensity they experienced. Testes size in the group in the lowest intensity (3 lux) increased faster than that in controls on short days of normal intensity, but they did not become photorefractory. Testes size increased in the groups on 13, 45, and 108 lux and subsequently became photorefractory. However, the 13- and 45-lux groups required more time to become photorefractory than did the 108-lux group. The responses observed were similar to those seen in starlings exposed to different photoperiods (e.g., 11 h light:13 h dark [11L:13D], 13L:11D, 16L:8D, 18L:6D), even though all were on the same 18L:6D photoperiod. Initially, the results appear to challenge the external coincidence model for photoperiodic time measurement, but consideration of the phase response curve of the circadian rhythm of photoinducibility in starlings and the way in which it might be affected by low light intensities refute this challenge.


EFFECTS OF MORTALITY RISK AND GROWTH ON A MODEL OF REPRODUCTIVE EFFORT: WHY THE SHINE AND SCHWARZKOPF MODEL IS NOT GENERAL.
Using data and reanalysis of a model published by Shine and Schwarzkopf (1992) we reject the two unsubstantiated assertions made by Shine et al. (1996) about modeling the evolution of reproductive effort in squamate reptiles: (1) mortality schedules do not affect predictions of the Shine and Schwarzkopf (1992) model; and (2) growth rates that would affect the predictions of the original model are biologically unreasonable. On the basis of these two points alone, we strongly reject Shine et al.'s (1996) claim that a critique by Niewiarowski and Dunham (1994) actually reinforces the original conclusions of Shine and Schwarzkopf (1992). Furthermore, results and data presented here are strong enough to severely circumscribe the generality of the Shine and Schwarzkopf (1992) model. Though we do not provide data or new analyses of the potential effects of offspring size variation, we reaffirm the position of Niewiarowski and Dunham (1994) that the sensitivity of the Shine and Schwarzkopf (1992) model to such effects should be explored before using it as a basis for structuring future research on the evolution of reproductive effort in squamate reptiles.


The effect of labor on olfactory exposure learning within the first postnatal hour.
Thirty-one neonates delivered by cesarean section were exposed to an odor for 30 min shortly after birth. Fifteen births had uterine labor contractions before delivery; 16 were without contractions. All babies were later tested (median age = 80 hr) for their responses to the familiar exposure odor and a novel odor presented on either side of the face. Overall, the babies spent more time turned toward the exposure odor than toward the novel scent. Babies in the labor condition, but not those bom without labor, displayed a significant preference for the exposure odor. Norepinephrine (NE) levels were higher in babies who oriented preferentially toward the exposure odor. Brief exposure immediately after birth is sufficient for the development of olfactory learning. Heightened learning by neonates from births with contractions may reflect locus coeruleus and NE activation. Olfactory learning may therefore be particularly efficient shortly after birth.


Manifestation of K+ transport alterations in cultured tumour cells of mice.
Sarcoma was induced by injection of human adenovirus type 12 into newborn, isogeneic CBA mice and maintained in adult female CBA mice by serial passages. Cells obtained from the tumours were cultivated by 3-4 passages in vitro. Normal fibroblastic cell cultures were gained by the same manner from isogeneic CBA mouse embryos. Characteristics of potassium transport in cultures of malignant cells and of normal fibroblastic cells were analysed. As a chemical tracer of K+ movements, 86Rb+ was applied. No significant difference could be detected either in the potassium concentration, or in the 86Rb+ uptake of the two types of cultured cells. However, when the cells were exposed to ouabain, the malignant cells showed a significantly reduced response, thus, the malignant cells accomplished a much less decrease in either cellular potassium concentration or in that of 86Rb+ uptake rate than the normal cells. These findings well fit the hypothesis advanced by several authors that malignant cells have a reduced density of ouabain receptor on the membrane.


Serosurveillance for Anaplasma phagocytophilum antibodies in white-tailed deer (Odocoileus virginianus) in Iowa, USA.
Cases of human granulocytic anaplasmosis have increased in number and are being identified in new geographic areas since its discovery in 1994. White-tailed deer (WTD) become infected with the causative agent, Anaplasma phagocytophilum, and serve as natural sentinels for this organism. In order to determine if A. phagocytophilum is present in the state of Iowa, sera collected from 628 WTD in 2004 from 13 sites and from 282 WTD in 1999 from a single, common site were tested by enzyme-linked immunosorbent assay and Western immunoblotting. A seroprevalence of 9.1% was found among the 2004 samples, and there was no change in seropositivity rates from 1999 to 2004 at the single, common site. As A. phagocytophilum is another tick-borne human pathogen to be identified in the state of Iowa, this study has important implications for health care providers.


Regulation of fructose uptake by glucose in Escherichia coli.
A mutant, DAI, has been isolated from the Escherichia coli K12, strain K2. 1t, as a colony resistant to 2-deoxyglucose (DG) when growing on fructose but still sensitive to DG when growing on other sugars. The mutation in DAI specifically affects the catabolite inhibition of fructose utilization by glucose and glucose-6-phosphate; the affected gene (designated cif) is located at min 41 on the E. coli linkage map and is highly co-transducible with the genes that specify the uptake of fructose (ptsF) and enzymic conversion of fructose-1-phosphate to fructose-1,6-bisphosphate (fpk).


Excess after stress-A three-study validation of the salzburg stress drinking scale as a new tool to measure the stress-drinking relationship.
Stress frequently influences a person's propensity to drink alcohol. Inter-individual differences in such stress-related drinking can be assessed through psychometric scales; however, available questionnaires conflate stress- with emotion-related reasons to drink and ignore evidence of decreased alcohol consumption in response to stress. Therefore, we developed a genuine stress-drinking scale (Salzburg Stress Drinking Scale; SSDS), adapted from the Salzburg Stress Eating Scale, and assessed its psychometric properties. In study 1 (n = 639), the SSDS was found to have a one-factor structure, excellent internal consistency, and acceptable test-retest reliability. SSDS scores were significantly correlated with other measures assessing emotional drinking, but uncorrelated with general alcohol pathology and other health-relevant consummatory behaviors such as stress-related eating or nicotine consumption. In addition, no significant sex differences arose. In study 2 (n = 42) patients with an alcohol use disorder or addiction scored significantly higher on the SSDS compared to healthy controls. In an Ecological Momentary Assessment study 3 (n = 67), the SSDS showed partial ecological validity through significant relationships with daily alcohol consumption, but not daily stress-drinking relationships. In sum, the SSDS represents a psychometrically sound tool for the measurement of stress-related drinking and complements a battery of stress-related changes in health-relevant behaviors.


[Effect of cerous nitrate on the activity of ATPase in tissues].
The effect of cerous nitrate on the activity of some ion-dependent ATPase such as Ca(2+)-ATPase, K+, Na(+)-ATPase and Mg(2+)-ATPase was studied in vivo. The results showed that Ca(2+)-ATPase, K+, Na(+)-ATPase and Mg(2+)-ATPase activity was increased in rat liver, kidney and heart after recurrent intraperitoneal administration of low dose of cerous nitrate(1 mg/kg), but no changes happened for these enzymes activity after high cerous nitrate administration(50 mg/kg). The mechanism of the phenomena was discussed.


Is pertussis immune globulin efficacious for the treatment of hospitalized infants with pertussis? No answer yet.
In a multicenter, randomized, placebo-controlled clinical trial of pertussis immune globulin, intravenous (P-IGIV), 25 infants hospitalized with pertussis were enrolled in 24 months (15% of the target sample size) before the study was prematurely terminated because of expiration of the P-IGIV lots and unavailability of additional study product. Although well tolerated, there was no difference in the number or rate of improvement of symptoms (paroxysmal cough, whoop, apnea, bradycardia, oxygen desaturations) in P-IGIV recipients compared with placebo.


940 nm Diode Laser assisted excision of Peripheral Ossifying Fibroma in a neonate.
Peripheral ossifying fibroma associated with neonatal tooth extraction is a rare, benign reactive lesion, but its nature and location often scares the patient & parents for possibility of neoplasm. A high recurrence rate makes its histopathological examination and long term follow up important. A 2 months old boy presented with enlarging soft tissue growth on the anterior mandibular ridge. The history revealed extraction of two neonatal teeth at 2 weeks of age. Lesion was excised using 940 nm diode laser and histopathological examination revealed hypercellularity and prominent dystrophic calcification, confirming it to be Peripheral Ossifying Fibroma. There was no recurrence after 18 months follow up. Paediatric dentists should be aware of possible outcomes of natal and neonatal teeth extraction and histopathological features of soft tissue lesions in neonates and infants. This report also highlights that 940 nm diode laser can be safely used for minor oral soft tissue surgeries in neonates and infants.


Interrogating transcriptional regulatory sequences in Tol2-mediated Xenopus transgenics.
Identifying gene regulatory elements and their target genes in vertebrates remains a significant challenge. It is now recognized that transcriptional regulatory sequences are critical in orchestrating dynamic controls of tissue-specific gene expression during vertebrate development and in adult tissues, and that these elements can be positioned at great distances in relation to the promoters of the genes they control. While significant progress has been made in mapping DNA binding regions by combining chromatin immunoprecipitation and next generation sequencing, functional validation remains a limiting step in improving our ability to correlate in silico predictions with biological function. We recently developed a computational method that synergistically combines genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to predict tissue-specific enhancers in the human genome. We applied this method to 270 genes highly expressed in skeletal muscle and predicted 190 putative cis-regulatory modules. Furthermore, we optimized Tol2 transgenic constructs in Xenopus laevis to interrogate 20 of these elements for their ability to function as skeletal muscle-specific transcriptional enhancers during embryonic development. We found 45% of these elements expressed only in the fast muscle fibers that are oriented in highly organized chevrons in the Xenopus laevis tadpole. Transcription factor binding site analysis identified >2 Mef2/MyoD sites within ~200 bp regions in 6 of the validated enhancers, and systematic mutagenesis of these sites revealed that they are critical for the enhancer function. The data described herein introduces a new reporter system suitable for interrogating tissue-specific cis-regulatory elements which allows monitoring of enhancer activity in real time, throughout early stages of embryonic development, in Xenopus.


Vascular and extravascular complications of liver transplantation: comprehensive evaluation with three-dimensional contrast-enhanced volumetric MR imaging and MR cholangiopancreatography.
Our purpose was to evaluate a comprehensive MR imaging strategy for recipients of liver transplants that relies on dynamic interpolated three-dimensional (3D) MR imaging for simultaneous vascular, parenchymal, and extrahepatic imaging. Twenty-three consecutive adult patients underwent 30 MR imaging examinations between 2 days and 99 months (mean, 15 months) after transplantation using a breath-hold 3D gradient-echo sequence (TR range/TE range, 3.7-4.7/1.8-1.9; flip angle, 12-30 degrees ) with an intermittent fat-saturation pulse and interpolation in the section-select direction to enable pixel size 3 mm or less in all dimensions. Unenhanced and triphasic contrast-enhanced 3D imaging (average dose, 0.13 mmol/kg of gadopentetate dimeglumine) was performed. A subset of patients (n = 13) also underwent MR cholangiopancreatography using half-Fourier single-shot turbo spin-echo imaging. MR imaging examinations were correlated with digital subtraction angiography (n = 8), contrast-enhanced cholangiography (n = 9), sonography (n = 13), and histopathology (n = 14). MR imaging revealed abnormal findings in 27 (90%) of 30 examinations, including vascular disease in nine, biliary complications in four, and evidence of intra- or extra-hepatic hepatocellular carcinoma recurrence in six. Digital subtraction angiography confirmed seven MR angiography examinations but suggested disease overestimation in one. Contrast-enhanced cholangiography confirmed findings of MR cholangiopancreatography in seven cases but suggested disease underestimation in two. Dynamic interpolated 3D MR imaging combined with dedicated MR cholangiopancreatography can provide a comprehensive assessment of vascular, biliary, parenchymal, and extrahepatic complications in most recipients of liver transplants.


Benzene exposures associated with tasks performed on marine vessels (circa 1975 to 2000).
In this article, we assemble and synthesize the available industrial hygiene data that describe exposure during the marine transport of benzene-containing products in the United States and abroad. A total of 25 studies were identified and summarized. The measured airborne concentrations of benzene on marine vessels were found to vary depending on several key factors, including the job task, vessel characteristics, cargo type, and sample type and duration. Despite the differences in sampling strategies and benzene content of the liquids being transported, personal time-weighted-average benzene air concentrations typically ranged from 0.2-2.0 ppm during closed loading and 2-10 ppm during open loading operations. Benzene exposures during these activities are likely due to specific short-term tasks, such as connecting and disconnecting hoses and tank gauging and sampling. Similar concentrations of benzene have been reported in the pump room during marine loading operations and during tank cleaning activities in various settings. When compared with contemporaneous occupational health standards, our review indicates that most activities performed on marine vessels from the 1970s to 1990s usually did not result in benzene exposures that exceeded these standards. The information and data presented here may be useful for quantitatively estimating or reconstructing historical exposures during the marine transport of benzene-containing cargo if details about individual's work histories in the maritime industry are available.


A simple and quick method to evaluate the influence of food price policy on population-based nutrition status and related nutrition intervention.
Food price policies have a major influence on population food choice and nutritional status, especially for low-income families. Therefore, simple and quick methods to evaluate their influence is desirable. Consistent with nutritional rationality and economical feasibility, a mathematical model was developed by Linear Programming to appraise the influence and rationality of the subsidization of egg and pork in Tianjin, using the data about food varieties and their prices in Tianjin in 1990. It was found that food subsidism to influence choice was not rational for improvement in nutritional status of low-income families. The concept, of "food choice space" was developed and its implications for nutrition intervention explored. The model developed can be used to judge the nutritional effect of food price policies and provide baseline data for nutrition intervention.


[Comparative study of microleakage by using different finished lines in selective laser melting metal crowns].
To evaluate microleakage of SLM Co -Cr alloy metal crown with two types finished line (chamfer and shoulder), compared with conventional fabrication of Co -Cr alloy metal crowns. Thirty healthy non-carious human molars were selected and randomly assigned to 3 groups, 10 in each. Teeth in group A and C received a chamfer finish line preparation, whereas teeth in group C received a shoulder finish line. Conventional Co -Cr alloy metal crowns were fabricated for group A when SLM metal crowns were made for group B and group C. Glass ionomer was applied for bonding. After 5000 thermocycles ranging from 5degrees centigrade to 55degrees centigrade,all the specimens were evaluated by dye penetration and then microleakage was examined under light microscope. The data were analyzed statistically with SPSS 20.0 software package. Microleakage in group A was significantly higher than the other two groups, group B and group C showed no significant difference in microleakage while microleakage in group B was higher than that in group C. Microleakage of SLM metal crowns was significantly less than that of conventional Co-Cr alloy metal crowns; chamfer finish line designs was recommended for SLM metal crowns in consideration of reducing microleakage and protecting tooth.


The Relationships Among Periodontitis, Pneumonia and COVID-19.
Periodontitis is a chronic inflammatory disease of the supporting structures of the teeth that affects approximately half of adults 30 years and older. There is increasing interest in the direct and indirect relationships between periodontitis and systemic diseases, including respiratory diseases. The aim of this study was to assess the evidence on links among periodontitis, pneumonia, and COVID-19. Oral and periodontal bacteria may be linked to respiratory disease directly by aspiration of pathogens into the lungs causing pneumonia. As SARS-CoV-2 began to spread worldwide in 2020, questions have arisen of how periodontal disease may also be connected to SARS-CoV-2 infection and severity, including potential replication and dissemination of the virus from periodontal pockets. Some proposed mechanisms include the oral cavity acting as a reservoir or point of entry for SARS-CoV-2, overgrowth of periodontal pathogens, and increased production of proinflammatory cytokines. Due to potential links between periodontal disease and respiratory infections like pneumonia and SARS-CoV-2, oral hygiene and management of periodontitis remain essential to help reduce infection and transmission of SARS-CoV-2.


Trifluoromethanesulfonic Acid Promoted Controllable Electrophilic Aromatic Nitration.
In this work, we developed a facile and controllable electrophilic aromatic nitration method with commercially available 68% HNO3 as the nitrating reagent and trifluoromethanesulfonic acid (HOTf) as the catalyst in hexafluoroisopropanol or under solvent-free conditions. The electrophilic nitration products of different arenes can be obtained in almost quantitative yields by tuning the loading of HOTf. The strong acidity and water absorbing property of HOTf allowed this transformation to reach completion in a short time at room temperature.


Case Report: Microcephaly in Twins due to the Zika Virus.
Recent studies have demonstrated an association between congenital Zika virus (ZIKV) infection and microcephaly; however, to date, there have been no reports on the consequences of ZIKV infection on fetuses in twin pregnancies. Herein, we reported on the first case of a monochorionic diamniotic (MCDA) twin pregnancy having ZIKV-related microcephaly. Our findings suggested that, in an MCDA twin pregnancy, the ZIKV may cause infection in both fetuses, resulting in severe abnormalities in the central nervous system due to neural cell destruction and the disruption of the normal development processes of the brain. This case report and other similar twin cases may help to understand the pathogenesis and to confirm the etiology of ZIKV as a teratogenic microorganism.


A case-control study: evaluation of vitamin D metabolism in patients with vitiligo.
Reduced vitamin D is considered as one of the environmental factors that can increase the prevalence of certain autoimmune diseases. This study aimed to assess vitamin D metabolism in patients with vitiligo. A prospective case-control study was conducted on 44 consecutive patients with vitiligo vulgaris and 43 healthy controls. Their plasma 25-hydroxyvitamin D (25(OH)D), parathormone (PTH), calcium, magnesium, and phosphate levels were measured. There was no significant difference in the mean age, sex and Fitzpatrick skin phototype between the patient and control groups (P > 0.05). The plasma levels of 25(OH)D and calcium were significantly decreased (P = 0.002, P < 0.0001, respectively) and PTH and magnesium levels were significantly increased in patients with vitiligo (P < 0.0001, P < 0.0001, respectively). The advancement of age (P = 0.03, R = -0.18) and comorbid autoimmune illnesses (P = 0.04) were found to be significantly associated with lower 25(OH)D levels. There is a universal lack of 25(OH)D in the Turkish population. Screening for vitamin D may be a tool for the presence of comorbid autoimmune diseases. Further studies are needed to understand the role of vitamin D metabolism in the pathogenesis of vitiligo.


Effects of lyophilized colostrum and different colostrum feeding regimens on passive transfer of immunoglobulin g in Majorera goat kids.
Three experiments were conducted including 180 Majorera kids. In the first experiment, the effect of use of lyophilized colostrum vs. frozen colostrum on immunoglobulin G (IgG) blood serum concentration was evaluated. Kids (n = 40) received the same management and IgG mass [3368 mg/kg of body weight (BW)] during the colostrum feeding period. The IgG in blood serum of kids from the lyophilized colostrum group was greater than that for kids that received frozen colostrum. The second experiment evaluated the effect of total IgG ingested by kids (n = 60) on IgG in blood serum during the colostrum feeding period. Three groups of animals received 3368, 1684, and 842 mg of IgG/kg of BW in 4 feedings for 2 d [high IgG concentration (H-IgG), medium IgG concentration (M-IgG), and low-IgG concentration (L-IgG), respectively]. The IgG blood serum in the kids that received H-IgG was greater than in the other 2 treatment groups, and no statistical differences were found for IgG in blood serum of kids that received either M-IgG or L-IgG. The third experiment evaluated the effect of timing of lyophilized colostrum meals on IgG blood serum concentration. Four groups of kids (n = 80) were used. Two groups received 1684 mg of IgG/kg of BW (higher level-1 d and higher level-2 d) and the other 2 groups received 842 mg of IgG/kg of BW (lower level-1 d and lower level-2 d). Two groups received 2 feedings in 1 d, and the other 2 groups received 4 feedings over a 2-d period, as denoted. Higher level-1 d kids had greater IgG blood serum concentration than the higher level-2 d kids, and no statistical differences were found between lower level-1 d and lower level-2 d kids.


Extrapulmonary oat-cell carcinoma presenting as a primary left ventricular tumor: a case report.
An asymptomatic 57-year-old man had an abnormal resting electrocardiogram and a positive treadmill stress test. Cardiac catheterization with left ventriculography revealed a large left ventricular mass in the apex, but otherwise normal coronary arteries. Excisional biopsy of the mass was consistent with oat-cell carcinoma. Additional evaluation was negative for metastasis. The patient was treated with combined chemoradiotherapy and was doing well at 16 months follow-up.


Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; application for strain differentiation by a novel typing method.
Mycobacterium tuberculosis complex strains contain a unique chromosomal region, which consists of multiple 36bp direct repeats (DRs), which are interspersed by unique spacers 35 to 41 bp in length. In this study we investigated the nature of the DNA polymorphism of this DR cluster by sequencing part of this region in a large number of M. tuberculosis complex strains. Two types of genetic rearrangements were observed. One type consists of the variation in one or a few discrete, contiguous DRs plus spacer sequences. This variation is probably driven by homologous recombination between adjacent or distant DRs. The other type of polymorphism is probably driven by transpositional events of the insertion sequence, IS6110, which is almost invariably present in the DR cluster of M. tuberculosis complex strains. Based on the nature of the DNA polymorphism in the DR cluster, we developed a novel method of strain differentiation, direct variable repeat polymer chain reaction (DVR-PCR), which enables typing of individual M. tuberculosis strains in a single PCR. The method allows an excellent differentiation of epidemiologically unrelated isolates and, in principle, the DVR-PCR allows the detection of M. tuberculosis and strain differentiation at the same time.


The influence of 1,3-dimethyl-5-adamantanamine (D-145) on catecholaminergic neurons of the rat brain, Histofluorescence studies.
The effect of a compound stimulating central dopaminergic structures, 1,3-dimethyl-5-adamantanamine (D-145), on the intensity of fluorescence in catecholaminergic nerve endings in some regions of the rat brain, mainly in the striatum and hypothalamus, was investigated with the modificated histofluorescence technique of Falck and Hillarp. D-145 (20 mg/kg), 2-3 hr after the administration depressed the intensity of catecholamine (CA) fluorescence in caudate-putamen (CP) and hypothalamic paraventricular nucleus (PVH). A blockade of dopamine (DA) receptors with spiperone (SPIRO, 2 mg/kg, 5 min before D-145) abolished the D-145 effect in PVH, thus indicating an indirect effect of D-145 on PVH, via a dopaminergic system. D-145 potentiated the depression of CA fluorescence produced by alpha-methyl-tyrosine methyl ester (H 44/68), 250 mg/kg ip. High doses of the CA synthesis inhibitor (2 X 400 mg/kg ip) prevented the developing of stimulation produced by D-145. These data indicate that the action of D-145 on DA receptors is indirect, via endogenous DA.


A Preliminary Investigation on the Antiviral Activities of the Philippine Marshmint (Mentha arvensis) Leaf Extracts against Dengue Virus Serotype 2 In Vitro.
In this study, we investigated the antiviral activity of lyophilized crude leaf extracts of the Philippine marshmint (Mentha arvensis L., commonly called yerba buena) against DENV-2 in vitro. The plant specimen was authenticated by DNA barcoding analysis using standard primers for amplification of rbcL, matK, ITS1, ITS2 and trnH-psbA. Aqueous, methanol and ethanol leaf extracts were prepared, and lyophilized prior to testing for its cytotoxicity and antiviral activities. All extracts presented cytotoxic activities against Vero cells in a dose-dependent manner. Half maximal cytotoxicity concentration (CC50) was calculated at 2,889.60 µg/mL for the aqueous extract, 1,928.62 µg/mL for the methanol extract, and 3,380.30 µg/mL for the ethanol extract. Antiviral activities assessed by plaque reduction assay revealed reduced DENV-2 viral infectivity, with the ethanol extract observed to have the strongest activity decreasing plaque numbers by 62% relative to the control. The methanol extract was observed to be most effective when added before infection causing 72% reduction in plaque numbers, whereas none of the extracts inhibited plaque formation by more than 40% when added after infection. DENV-2 NS1 antigen production was significantly reduced by the methanol extract, while viral RNA levels were also decreased as determined by real time RT-PCR. Phytochemical analysis revealed the presence of flavonoids, phenolics, tannins, proteins, reducing sugars and saponins. Our preliminary results are promising, however, it should be interpreted with caution as further studies are needed to establish its potential therapeutic application against dengue infection.


Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline.
Chronic pulmonary hypertension is associated with significant vascular remodeling. We demonstrated recently in the monocrotaline (MCT) and chronic hypoxia rat models of pulmonary hypertension that treatment with platelet-activating factor (PAF) antagonists inhibited the development of chronic pulmonary hypertension. PAF and other lipid mediators interact with interleukin-1. We postulated that chronic treatment with a recombinant human interleukin-1 receptor antagonist (IL-1ra) would inhibit development of chronic pulmonary hypertension in animal models. Rats were either injected with (60 mg/kg) MCT or exposed to a stimulated high altitude of 16,000 feet; half of the animals were treated with twice-daily injections (2 mg/kg) of IL-1ra. At 3 wk after MCT injection or 3 wk of hypoxic exposure, pulmonary artery pressure and right heart ventricle weight/(left ventricle and septum weight), RV/(LV + S), were measured. IL-1ra treatment reduced pulmonary hypertension and right heart hypertrophy in the MCT model, but not in the chronic hypoxia model. Measurement of lung homogenate IL-1 alpha by radioimmunoassay showed elevated levels in the MCT-treated rats throughout the 3-wk observation period. IL-1ra treatment reduced the levels of IL-1 alpha in lung tissue in most of the MCT-treated rats. MCT treatment was also associated with an increase in lung mRNA for IL-1 alpha, IL-1 beta, and IL-1ra. Immunohistology, using an antibody against rat IL-1 alpha, revealed staining of alveolar structures and of vascular and bronchial smooth muscle. In situ hybridization using a human IL-1 alpha cDNA probe demonstrated increased expression of the IL-1 alpha gene in the lung cells after endotoxin or MCT treatment. Northern blot analysis demonstrated low-level expression of IL-1 alpha mRNA in extracts of normal rat lung and increased expression after endotoxin or MCT treatment. We conclude that chronic treatment with human IL-1ra inhibited the development of pulmonary hypertension in the inflammatory (MCT) model, but not in the chronically hypoxic rats. This result indicates that IL-1 participates in the pathogenesis of some forms of pulmonary hypertension.


[The value of electronic film for improving the quality of hospital services].
In this paper, by describing and comparing different implementations of electronic film combined with the actual application of the electronic film in the imaging department and the clinical departments. We elaborate electronic film for optimizing the imaging department workflow to improve service quality and patient satisfaction and other aspects of value.


Influence of CR3 (CD11b/CD18) expression on phagocytosis of Bordetella pertussis by human neutrophils.
CR3 (CD11b/CD18) is expressed on neutrophils, and the engagement of CR3 can promote phagocytosis. CR3 serves as the receptor for the Bordetella pertussis adhesin filamentous hemagglutinin (FHA) and for the adenylate cyclase toxin (ACT), which blocks neutrophil function. The influence of CR3, FHA, and ACT on the phagocytosis of B. pertussis by human neutrophils was examined. The surface expression and function of CR3 are regulated. Tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) increased CR3 surface expression, but only TNF-alpha increased the ability of neutrophils to phagocytose B. pertussis, suggesting that elevated CR3 expression alone is not sufficient to promote phagocytosis. Purified FHA and pertussis toxin also increased the surface expression of CR3 on neutrophils, while ACT and the B subunit of pertussis toxin did not affect CR3 expression. FHA-mediated attachment to CR3 can lead to phagocytosis, especially in the absence of ACT. FHA mutants failed to attach and were not phagocytosed by neutrophils. Similarly, an antibody to CR3 blocked both attachment and phagocytosis. The addition of exogenous FHA enhanced the attachment and phagocytosis of wild-type B. pertussis and FHA mutants. Mutants lacking the SphB1 protease, which cleaves FHA and allows the release of FHA from the bacterial surface, were phagocytosed more efficiently than wild-type bacteria. ACT mutants were efficiently phagocytosed, but wild-type B. pertussis or ACT mutants plus exogenous ACT resisted phagocytosis. These studies suggest that the activation and surface expression of CR3, FHA expression, and the efficiency of ACT internalization all influence whether B. pertussis will be phagocytosed and ultimately killed by neutrophils.


A signature of cosmic-ray increase in AD 774-775 from tree rings in Japan.
Increases in (14)C concentrations in tree rings could be attributed to cosmic-ray events, as have increases in (10)Be and nitrate in ice cores. The record of the past 3,000 years in the IntCal09 data set, which is a time series at 5-year intervals describing the (14)C content of trees over a period of approximately 10,000 years, shows three periods during which (14)C increased at a rate greater than 3‰ over 10 years. Two of these periods have been measured at high time resolution, but neither showed increases on a timescale of about 1 year (refs 11 and 12). Here we report (14)C measurements in annual rings of Japanese cedar trees from ad 750 to ad 820 (the remaining period), with 1- and 2-year resolution. We find a rapid increase of about 12‰ in the (14)C content from ad 774 to 775, which is about 20 times larger than the change attributed to ordinary solar modulation. When averaged over 10 years, the data are consistent with the decadal IntCal (14)C data from North American and European trees. We argue that neither a solar flare nor a local supernova is likely to have been responsible.


Causes of death in hospitalized adults with a premortem diagnosis of tuberculosis: an autopsy study.
To ascertain the immediate and underlying causes of death in adults who died in hospital with a premortem diagnosis of tuberculosis. Causes of death were assessed independently by internists and pathologists in 50 adults admitted to two Soweto hospitals who died 24 h or more after admission. Detailed record reviews and complete autopsies, including HIV tests when not performed premortem, were performed. In addition, a variety of postmortem microbiological tests were performed. Forty-seven patients had HIV infection; all were antiretroviral naive. Their median age was 34.5 years, median CD4 cell count was 48 cells/microl and median length of hospitalization before death was 6 days. Autopsy confirmed the premortem diagnosis of tuberculosis in 37 HIV-infected patients (79%), whereas 10 (21%) did not demonstrate tuberculosis. Bronchopneumonia and cytomegalovirus pneumonitis were the leading pathologies in these 10 patients. In 47 HIV-infected cadavers immediate or contributory causes of death were: extensive pulmonary tuberculosis, 32 (68%); disseminated tuberculosis, 28 (60%); bacterial pneumonia, 13 (26%); cytomegalovirus pneumonitis in seven (15%); cytomegalovirus DNA was found in 31 (66%) and Pneumocystis pneumonia was found in five cadavers (11%). The lung, followed by lymph nodes, liver and kidney, were the commonest sites of tuberculosis. Mycobacterium tuberculosis was cultured from 19 spleens, one of which was multidrug resistant, and Salmonella spp. was cultured from 11 splenic specimens. We demonstrated disseminated, extensive tuberculosis associated with advanced HIV disease. Severe bacterial infections, including salmonellosis, were the leading co-morbidity, suggesting that hospitalized HIV-infected adults in whom tuberculosis is suspected may benefit from broad-spectrum antibiotic therapy.


Screening, recognition and quantitation of salbutamol residues in ham sausages by molecularly imprinted solid phase extraction coupled with high-performance liquid chromatography-ultraviolet detection.
A highly selective molecularly imprinted solid phase extraction (MISPE) coupled with liquid chromatography-ultraviolet detection was developed for the determination of salbutamol (SAL) in ham sausages. New molecularly imprinted polymers (MIPs) were synthesized with phenylephrine as dummy template and it revealed good affinity to SAL in methanol-acetonitrile system. Adsorption capacity of the MIPs was evaluated by dynamic adsorption experiments. The MIPs were used as SPE sorbent for the selective clean-up and pre-concentration of SAL in ham sausage samples. The results showed that the matrix compounds presented in ham sausage samples could be removed effectively and the recoveries of SAL at three spiked levels were ranged from 82.6 to 100.5% with the relative standard deviation (RSD) of less than 3.6%. This method is simple and sensitive, and is therefore an alternative tool to the existing methods for analyzing residual SAL in biological samples.


Supramolecular Polyurethane "Ligaments" Enabling Room-Temperature Self-Healing Flexible Perovskite Solar Cells and Mini-Modules.
Flexible perovskite solar cells (F-PSCs) have emerged as promising alternatives to conventional silicon solar cells for applications in portable and wearable electronics. However, the mechanical stability of inherently brittle perovskite, due to residual lattice stress and ductile fracture formation, poses significant challenges to the long-term photovoltaic performance and device lifetime. In this paper, to address this issue, a dynamic "ligament" composed of supramolecular poly(dimethylsiloxane) polyurethane (DSSP-PPU) is introduced into the grain boundaries of the PSCs, facilitating the release of residual stress and softening of the grain boundaries. Remarkably, this dynamic "ligament" exhibits excellent self-healing properties and enables the healing of cracks in perovskite films at room temperature. The obtained PSCs have achieved power conversion efficiencies of 23.73% and 22.24% for rigid substrates and flexible substrates, respectively, also 17.32% for flexible mini-modules. Notably, the F-PSCs retain nearly 80% of their initial efficiency even after subjecting the F-PSCs to 8000 bending cycles (r = 2 mm), which can further recover to almost 90% of the initial efficiency through the self-healing process. This remarkable improvement in device stability and longevity holds great promise for extending the overall lifetime of F-PSCs.


[Plasma Renin Activity and Potential of Indapamide Retard to Improve Control of Hypertension].
to study plasma renin activity (PRA) as a predictor of antihypertensive response to addition of diuretic to combination of angiotensin-converting enzyme inhibitor (ACEI) and calcium antagonist (CA). The study included 72 patients (39% men, mean age 62.0+/-8.3 years) with uncontrolled despite use of ACEI and CA arterial hypertension (AH) without overt associated clinical conditions (AH criteria of national guidelines, 2010). After 4 weeks of therapy with ACE inhibitor (quadropril 6 mg/day) and CA (felodipine 5 mg/day) in all patients who did not reach target level of blood pressure (BP) (clinical BP more or equal 140/90 mm Hg, daytime BP according to ambulatory BP monitoring [ABPM] >135/85 mm Hg) indapamide retard (1.5 mg/day) was added to combination therapy for 6 months. Examination included measurement of baseline and on treatment PRA and repetitive ABPM. More pronounced antihypertensive response was observed in the group of patients with volume dependent AH. Baseline BP was 156.6+/-14.1/86.7+/-1.5 and 151.9+/-17.1/78.0+/-7.8 mm Hg, on treatment level of clinical BP - 126.2+/-10.6/72.5+/-11.6 and 132.2+/-9.1/71.9+/-7.2 mm Hg (p<0.05) in patients with volume dependent and renin dependent AH, respectively. Target clinical BP was achieved in 95 and 80% of patients, respectively (2=10.3; p<0.05). According to ABPM both daytime and nighttime on treatment BP was lower in the group of patients with volume dependent AH (130.0+/-11.0/74.1+/-9.9 vs. 136.5+/-7.3/78.8+/-8.2 mm Hg, p<0.05; and 127.9+/-15.8/71+/-13.5 vs. 132.6+/-13.0/74.5+/-10.2 mm Hg, p<0.05). PRA is an independent predictor of antihypertensive response to addition of a diuretic to combination therapy with ACEI and CA.


Disposition decisions in a walk-in clinic: social and psychiatric variables.
The success of a walk-in clinic in providing care without regard to social and diagnostic factors is measured in a study of 391 patients. Results indicate that acceptance or nonacceptance into the clinic system were unrelated to social class or diagnosis, although these factors did influence referrals to specific clinic resources.


Therapeutic drug monitoring for antidepressant drug treatment.
The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.


Review of usnic acid and Usnea barbata toxicity.
Usnic acid is a prominent secondary lichen metabolite that has been used for various purposes worldwide. Crude extracts of usnic acid or pure usnic acid have been marketed in the United States as dietary supplements to aid in weight loss. The US Food and Drug Administration (FDA) received 21 reports of liver toxicity related to the ingestion of dietary supplements that contain usnic acid. This prompted the FDA to issue a warning about one such supplement, LipoKinetix, in 2001 (http://www.cfsan.fda.gov/~dms/ds-lipo.html). Subsequently, usnic acid and Usnea barbata lichen were nominated by the National Toxicology Program (NTP) for toxicity evaluations. At present, a toxicological evaluation of usnic acid is being conducted by the NTP. This review focuses on the recent findings of usnic acid-induced toxicities and their underlying mechanisms of action.


Catalytic synthesis of renewable phenol derivatives from biobased furanic derivatives.
Here, we study a sequence Diels-Alder/aromatization reaction between biobased furanic derivatives and alkynes, paving the way to renewable phenols. Guided by DFT calculations, we revealed that, in the case of dimethylfuran, the methyl group can migrate during the aromatization step, making this substrate also eligible to access renewable phenols. This reaction has been then successfully transposed to furfural and furfuryl alcohol, allowing molecular diversity and complexity to be created on phenol ring starting from two cheap biobased furanic derivatives available on large scale.


Arthroscopic autologous chondrocyte transplantation: technical note.
We describe an arthroscopic surgical technique for tissue engineered cartilage grafting. A three-dimensional hyaluronic acid support is used for autologous chondrocyte culturing. The technique reduces morbidity of classic autologous implant and avoids open surgery and the use of a periosteal flap. The procedure includes the advantages of arthroscopic osteochondral grafting without donor site morbidity. With this technique is possible to reduce the patient morbidity, time and cost of surgery.


The disc damage likelihood scale: Diagnostic accuracy and correlations with cup-to-disc ratio, structural tests and standard automated perimetry.
Our objective was to compare the diagnostic accuracies of and to determine the correlations between the disc damage likelihood scale (DDLS) and anatomical and functional tests used for glaucoma detection. A total of 54 healthy subjects (54 eyes) and 47 primary open-angle glaucoma patients (47 eyes) were included in this cross-sectional observational study. DDLS scores and cup-to-disc (C/D) ratios were evaluated. Subjects underwent standard automated perimetry (SAP), optic disc and retinal nerve fiber layer (RNFL) imaging with time and spectral-domain optical coherence tomography (TD and SD-OCT), Heidelberg Retina Tomograph (HRT II), and scanning laser polarimetry (GDx-VCC). Areas under the receiver operating characteristic curves (AROCs) for DDLS and diagnostic tests parameters were calculated. DDLS correlations (Spearman's rank) among these parameters were analyzed. Fifty-four eyes were healthy and 47 had glaucoma, including 16 preperimetric glaucoma. DDLS, vertical and horizontal C/D ratios had the largest AROCs (0.92, 0.94 and 0.91, respectively). DDLS diagnostic accuracy was better than the accuracies of HRT II parameters, TD and SD-OCT RNFL thicknesses, and SAP mean deviation (MD) index. There were no significant differences between the accuracies of the DDLS and the C/D ratios, TD-OCT vertical (0.89) and horizontal (0.86) C/D ratios, TD-OCT C/D area ratio (0.89), and GDx-VCC NFI (0.81). DDLS showed significant strong correlations with vertical (r = 0.79) and horizontal (0.74) C/D ratios, and with the parameters vertical C/D ratio and C/D area ratio from HRT II (both 0.77) and TD-OCT (0.75 and 0.72, respectively). DDLS had significant moderate correlations with most of the other structural measurements and SAP MD. The optic disc clinical evaluation with DDLS system and C/D ratio demonstrated excellent accuracy in distinguishing glaucomatous from healthy eyes. DDLS had moderate to strong correlations with most structural and functional parameters. These findings stress the importance of optic disc clinical examination to detect glaucoma in a clinical scenario.


UV-Light-Induced Improvement of Fluorescence Quantum Yield of DNA-Templated Gold Nanoclusters: Application to Ratiometric Fluorescent Sensing of Nucleic Acids.
The use of DNA as a template has been demonstrated as an effective method for synthesizing different-sized silver nanoclusters. Although DNA-templated silver nanoclusters show outstanding performance as fluorescent probes for chemical sensing and cellular imaging, the synthesis of DNA-stabilized gold nanoclusters (AuNCs) with high fluorescence intensity remains a challenge. Here a facile, reproducible, scalable, NaBH4-free, UV-light-assisted method was developed to prepare AuNCs using repeats of 30 adenosine nucleotides (A30). The maximal fluorescence of A30-stabilized AuNCs appeared at 475 nm with moderate quantum yield, two fluorescence lifetimes, and a small amount of Au(+) on the surface of the Au core. Results of size-exclusion chromatography revealed that A30-stabilized AuNCs were more compact than A30. A series of control experiments showed that UV light played a dual role in the reduction of gold-ion precursors and the decomposition of citrate ions. A30 also acted as a stabilizer to prevent the aggregation of AuNCs. In addition, single-stranded DNA (ssDNA) consisting of an AuNC-nucleation sequence and a hybridization sequence was utilized to develop a AuNC-based ratiometric fluorescent probe in the presence of the double-strand-chelating dye SYBR Green I (SG). Under conditions of single-wavelength excitation, the combination of AuNC/SG-bearing ssDNA and perfectly matched DNA emitted fluorescence at 475 and 525 nm, respectively. The formed AuNC/SG-bearing ssDNA enabled the sensitive, selective, and ratiometric detection of specific nucleic acid targets. Finally, the AuNC-based ratiometric probes were successfully applied to determine specific nucleic acid targets in human serum.


A heminested polymerase chain reaction for the detection of Brazilian rabies isolates from vampire bats and herbivores.
A heminested-PCR (hn-PCR) using primers to the nucleoprotein-coding gene in a nested set was evaluated in the detection of Brazilian strains of rabies virus (RV). A representative number of RV nucleoprotein sequences belonging to genotype 1 were aligned. Based on such alignment, primers were directed to highly conserved regions. All 42 clinical samples positive by both fluorescent antibody and mouse inoculation tests were also positive by the hn-PCR. Brain tissue that had been left to decompose, obtained from an experimentally inoculated mouse was tested by hn-PCR and yielded positive results. In conclusion, primers designed here were capable of amplifying Brazilian RV isolates obtained from a rural epidemiological cycle.


T lymphocyte activation in euthyroid Graves' ophthalmopathy: soluble interleukin 2 receptor release, cellular interleukin 2 receptor expression and interleukin 2 production.
The present study was undertaken to examine the cellular control arm of the immune response with regard to T lymphocyte proliferation in euthyroid Graves' ophthalmopathy. Twenty patients with euthyroid Graves' ophthalmopathy (7 on antithyroid drugs and 13 on no treatment) and 18 healthy controls were studied in an infection-free period. Mitogen-stimulated cellular interleukin 2 (IL2) receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production, were studied in peripheral blood mononuclear cells cultured for 24 h. The cellular IL2 receptor expression and soluble IL2 receptor release did not differ between the patients and healthy controls. In contrast, IL2 production in response to pokeweed mitogen stimulation was increased in lymphocytes from patients with Graves' ophthalmopathy. The IL2 release did not correlate with the quantities of cellular and soluble IL2 receptor. The mitogen-stimulated cellular IL2 receptor expression, IL2 receptor release, and IL2 production did not differ between patients with or without carbimazole therapy. Despite a suggested role of autoreactive T cells in mediating the development and propagation of autoimmune thyroid disease, this study fails to demonstrate a defective T lymphocyte activation state in patients with Graves' ophthalmopathy during an euthyroid state.


The distribution of aggregating proteoglycans in articular cartilage: comparison of quantitative immunoelectron microscopy with radioimmunoassay and biochemical analysis.
Electron microscopic immunolocalization and radioimmunoassay have been used to determine the variation with depth of the hyaluronate-binding region of proteoglycan in articular cartilage. The cartilage was cut into serial sections from the articular surface to the bony margin, the proteoglycans were extracted from each section and determined by radioimmunoassay using antibodies raised against proteoglycan binding region. Proteoglycans were found to be most abundant in the middle zone and least abundant near the articular surface. Biochemical analysis for hexuronate in the same extracts showed a distribution of proteoglycan in agreement with these and other published results. The binding region antiserum was used for electron microscopic immunolocalization of proteoglycan with ultrathin sections of cartilage embedded in Lowicryl K4M resin. After digestion of the sections with chondroitinase ABC, the proteoglycans were localized using the antiserum and protein A-coated gold particles as immunolabel. The density of labeling was quantified using a Magiscan image analysis system. Throughout the depth of the cartilage matrix labeling was higher in the pericellular regions compared to the intercellular regions, and variation of the amount of immunolabel with depth was found to show a good correlation with the results from radioimmunoassay. Intracellular labeling of proteoglycans was mainly found over the Golgi region and in membrane-bound (secretory) vesicles.


Long-term renal function in pediatric liver and heart recipients.
Long-term survivors of pediatric liver and heart transplantation are at risk for progressive renal dysfunction as a result of chronic exposure to calcineuron inhibitors. This class of drugs causes alterations in renal perfusion that can result in irreversible renal injury including afferent arteriopathy, glomerulosclerosis, tubular atrophy and interstitial fibrosis. Approximately 3-6% of pediatric liver and heart recipients will develop end stage renal failure. A much larger percentage has chronic renal insufficiency and hypertension. Children with significant renal compromise in the pretransplant period and those with significantly elevated serum creatinine levels during the first post-transplant year may be at the highest risk to develop irreversible renal injury in long-term follow-up. Serum creatinine is a poor screening tool as it rises late in the course when the injury may no longer be reversible. Strategies to minimize long-term exposure to calcineuron inhibitors may reduce the prevalence of renal insufficiency in this vulnerable population.


Public Policy and the Next Generation of Farmers, Ranchers, Producers, and Agribusiness Leaders.
The emerging, next generation of people engaged as managers in agriculture differs from the "baby boomer" farm generation that relishes certain traditions and an agrarian lifestyle. These futuristic producers and managers have been raised in a society that promulgates safety environment rules. They have witnessed lives saved by automobile seatbelts and lives improved from clean air and water. They know the basic cost of effective safety compliance is relatively fixed, regardless of the number of employees, and they are willing to invest resources that ensure a culture of safety, because it is economically beneficial, socially responsible, and probably required by the companies to whom they need to market their products. These same millennials understand that society and their customers will not continue to tolerate the high rate of agricultural injuries and deaths indefinitely. Public policy as a means to improve agricultural workers' safety and health is likely to be less resisted by the next generation of farmers, ranchers, producers, and agribusiness leaders who, regardless of legal or regulatory pressure, will implement internal business policies emphasizing safety, health, sustainability, and social justness as they understand it.


Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation.
The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0-1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2-3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in addition to tumor response after neoadjuvant therapy. Baseline NLR could be a useful candidate factor for stratifying patients and making treatment decisions in locally advanced rectal cancer.


Systematic Review of WHO Grade 4 Astrocytoma in the Cerebellopontine Angle: The Impact of Anatomic Corridor on Treatment Options and Outcomes.
Background Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. Methods A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Results Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. Conclusion The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.


Chemokine Heteromers and Their Impact on Cellular Function-A Conceptual Framework.
Chemoattractant cytokines or chemokines are proteins involved in numerous biological activities. Their essential role consists of the formation of gradient and (immune) cell recruitment. Chemokine biology and its related signaling system is more complex than simple ligand-receptor interactions. Beside interactions with their cognate and/or atypical chemokine receptors, and glycosaminoglycans (GAGs), chemokines form complexes with themselves as homo-oligomers, heteromers and also with other soluble effector proteins, including the atypical chemokine MIF, carbohydrate-binding proteins (galectins), damage-associated molecular patterns (DAMPs) or with chemokine-binding proteins such as evasins. Likewise, nucleic acids have been described as binding targets for the tetrameric form of CXCL4. The dynamic balance between monomeric and dimeric structures, as well as interactions with GAGs, modulate the concentrations of free chemokines available along with the nature of the gradient. Dimerization of chemokines changes the canonical monomeric fold into two main dimeric structures, namely CC- and CXC-type dimers. Recent studies highlighted that chemokine dimer formation is a frequent event that could occur under pathophysiological conditions. The structural changes dictated by chemokine dimerization confer additional biological activities, e.g., biased signaling. The present review will provide a short overview of the known functionality of chemokines together with the consequences of the interactions engaged by the chemokines with other proteins. Finally, we will present potential therapeutic tools targeting the chemokine multimeric structures that could modulate their biological functions.


Idiopathic dilatation of the submandibular gland duct.
Lithiasis and stenosis may cause salivary duct dilatation due to the increased pressure in the duct upstream of the obstruction. Idiopathic dilatations, also called megaducts, with no associated increase in pressure, have only been described in the parotid gland. The aim of this study was to describe the characteristics of submandibular duct dilatation unrelated to lithiasis, stenosis, or an imperforate duct, to report the existence of submandibular megaducts. This retrospective single-centre study included patients treated at La Conception University Hospital, Marseille, France, between 2007 and 2019. Patients with submandibular duct dilatation of ≥4 mm confirmed by magnetic resonance imaging sialography (sialo-MRI), who also underwent sialendoscopy to identify any associated stenosis, were included. Patients with lithiasis, stenosis, an imperforate ostium, or a history of trauma or surgery to the floor of the mouth were excluded. Five patients (three female, two male) aged 30-76 years with idiopathic duct dilatations in nine submandibular glands were included. The most commonly reported symptoms were submandibular swelling, pruritus, and discomfort, mostly outside mealtimes. Recurrence of symptoms after treatment was frequent. This study is novel in describing submandibular megaducts as opposed to dilatation caused by high pressure associated with stenosis, with confirmation by sialo-MRI and sialendoscopy.


Seizures induced by desloratadine, a second-generation antihistamine: clinical observations.
Some clinical experiences indicate that H1-antihistamines, especially first-generation H1-antagonists, occasionally provoke convulsions in healthy children as well as epileptic patients. Desloratadine is a frequently used second-generation antihistamine considered to be effective and safe for the treatment of allergic diseases. We describe four children who experienced epilepsy associated with the nonsedating H(1)-antagonist desloratadine and discuss the neurophysiologic role of the central histaminergic system in seizure susceptibility. In conclusion, we recommend caution in treating epileptic patients with the histamine H(1)-antagonists, including second- and third-generation drugs that are frequently referred because they are considered to be nonsedating antihistamines.


Silica Cross-Linked Micellar Core--Shell Nanoparticles Encapsulating IR-780 with Strong Bright and Good Biocompatibility for Optical Imaging In Vivo.
IR-780 iodide, a near-infrared (NIR) fluorescent heptamethine dye, has attracted wide attention in the biomedical community. However, hydrophobicity and toxicity severely limit its further biomedical application. Although many successful efforts have been made to increase its solubility and biocompatibility, a strong fluorescent signal and longer retention time are in high demand in biomedical application in vivo as well as basic science research. In this work, we report the development of novel silica cross-linked micellar core–shell nanoparticles encapsulating IR-780 (NIR-Silica NPs) and their utility for biomedical imaging in vivo. Compared to free IR-780, the solubility of NIR-Silica NPs was not only greatly increased, but there was also a dramatic 5–7-fold enhancement of fluorescence intensity. More importantly, the exceptionally small size (25 nm) and colloidal stability of the NPs are also sufficient to realize the enhanced permeability and retention effect. In vitro cell viability assays further indicated that the NIR-Silica NPs are safer even at the highest concentration tested of 1.0 mg/mL. Finally, sentinel lymph node mapping and long-term tumor imaging in vivo demonstrated that the NIR-Silica NPs have a long circulation time and higher signal-to-noise ratio at a very low dye concentration and short exposure time (0.2 s). Therefore, the NIR-Silica NPs may be a promising fluorescence imaging agent for clinical application.


Identification of residues in TIP47 essential for Rab9 binding.
TIP47 (tail-interacting protein of 47 kDa) binds to the cytoplasmic domains of the cation-dependent and cation-independent mannose 6-phosphate receptors (MPRs) and is required for their transport from endosomes to the trans-Golgi network in vitro and in living cells. TIP47 recognizes distinct determinants in the cytoplasmic domains of these two receptors, and its ability to bind to the cation-independent MPR is enhanced by the concomitant binding of the Rab9 GTPase. We show here that TIP47 residues 161-169 are essential, but likely not sufficient, for Rab9 binding. Mutation of these residues led to a significant decrease in Rab9 binding, but did not alter the global folding of the protein. The most impaired mutant was indistinguishable from wild-type TIP47 in its circular dichroism spectrum, and mutant proteins that showed decreased Rab9 binding retained full capacity to bind to MPR cytoplasmic domains. Closely related sequences in a related protein, adipophilin, did not confer Rab9 binding capacity to that protein. Partial proteolysis of TIP47 and TIP47 mutant proteins revealed subtle conformational differences, suggesting that residues 161-169 reside in a portion of TIP47 that is important for its conformation. These experiments reveal distinct binding domains for the Rab9 GTPase and MPR cytoplasmic domains in the cargo selection protein TIP47.


Gene expression-based biological test for major depressive disorder: an advanced study.
Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD. This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively. Further research to identify MDD-specific markers is needed to improve the performance of this biological test.


Profile of women in a county jail.
The literature about women in prison says little about characteristics of women in local jails. The goal of this study was to better understand the demographics and characteristics of these women to develop responsive programming. A cross-sectional survey of 346 women in an urban jail was conducted. Descriptive statistics were generated, and a logistic regression analysis was performed to examine contributors to multiple arrests. Of the 346 women surveyed, 65.3% were incarcerated for minor charges and 58.9% had been incarcerated four or more times. Of those with children, the majority had children younger than 18, and nearly 30% had children younger than 5. Partner abuse and involvement in the juvenile justice system were significantly related to multiple arrests. These findings indicated that many women in jail are caught in a cycle of multiple arrests and violence, with many of their children likewise involved.


Single umbilical artery and umbilical cord torsion leading to fetal death. A case report.
Intrauterine fetal death is a complication that cannot often be predicted by standard obstetric management. Cord accident may be responsible for about 5% of cases. Umbilical cord torsion is an extremely rare cause of intrauterine fetal death. An 18-year-old, nulliparous woman presented with a complaint of decreased fetal movement at 38 weeks' gestation. Intrauterine fetal death was diagnosed on ultrasound. The pathologic examination revealed umbilical cord torsion and confirmed a single umbilical artery that was diagnosed on ultrasound. Umbilical cord torsion that leads to intrauterine fetal death is extremely rare. A pregnancy with a single umbilical artery may need fetal monitoring during the third trimester.


NADPH oxidase and hydrogen peroxide mediate insulin-induced calcium increase in skeletal muscle cells.
Skeletal muscle is one of the main physiological targets of insulin, a hormone that triggers a complex signaling cascade and that enhances the production of reactive oxygen species (ROS) in different cell types. ROS, currently considered second messengers, produce redox modifications in proteins such as ion channels that induce changes in their functional properties. In myotubes, insulin also enhances calcium release from intracellular stores. In this work, we studied in myotubes whether insulin stimulated ROS production and investigated the mechanisms underlying the insulin-dependent calcium increase: in particular, whether the late phase of the Ca2+ increase induced by insulin required ROS. We found that insulin stimulated ROS production, as detected with the probe 2',7'-dichlorofluorescein diacetate (CM-H2DCFDA). We used the translocation of p47phox from the cytoplasm to the plasma membrane as a marker of the activation of NADPH oxidase. Insulin-stimulated ROS generation was suppressed by the NADPH oxidase inhibitor apocynin and by small interfering RNA against p47phox, a regulatory NADPH oxidase subunit. Additionally, both protein kinase C and phosphatidylinositol 3-kinase are presumably involved in insulin-induced ROS generation because bisindolylmaleimide, a nonspecific protein kinase C inhibitor, and LY290042, an inhibitor of phosphatidylinositol 3-kinase, inhibited this increase. Bisindolylmaleimide, LY290042, apocynin, small interfering RNA against p47phox, and two drugs that interfere with inositol 1,4,5-trisphosphate-mediated Ca2+ release, xestospongin C and U73122, inhibited the intracellular Ca2+ increase produced by insulin. These combined results strongly suggest that insulin induces ROS generation trough NADPH activation and that this ROS increase is required for the intracellular Ca2+ rise mediated by inositol 1,4,5-trisphosphate receptors.


Compensating for geographic variation in detection probability with water depth improves abundance estimates of coastal marine megafauna.
The probability of an aquatic animal being available for detection is typically <1. Accounting for covariates that reduce the probability of detection is important for obtaining robust estimates of the population abundance and determining its status and trends. The dugong (Dugong dugon) is a bottom-feeding marine mammal and a seagrass community specialist. We hypothesized that the probability of a dugong being available for detection is dependent on water depth and that dugongs spend more time underwater in deep-water seagrass habitats than in shallow-water seagrass habitats. We tested this hypothesis by quantifying the depth use of 28 wild dugongs fitted with GPS satellite transmitters and time-depth recorders (TDRs) at three sites with distinct seagrass depth distributions: 1) open waters supporting extensive seagrass meadows to 40 m deep (Torres Strait, 6 dugongs, 2015); 2) a protected bay (average water depth 6.8 m) with extensive shallow seagrass beds (Moreton Bay, 13 dugongs, 2011 and 2012); and 3) a mixture of lagoon, coral and seagrass habitats to 60 m deep (New Caledonia, 9 dugongs, 2013). The fitted instruments were used to measure the times the dugongs spent in the experimentally determined detection zones under various environmental conditions. The estimated probability of detection was applied to aerial survey data previously collected at each location. In general, dugongs were least available for detection in Torres Strait, and the population estimates increased 6-7 fold using depth-specific availability correction factors compared with earlier estimates that assumed homogeneous detection probability across water depth and location. Detection probabilities were higher in Moreton Bay and New Caledonia than Torres Strait because the water transparency in these two locations was much greater than in Torres Strait and the effect of correcting for depth-specific detection probability much less. The methodology has application to visual survey of coastal megafauna including surveys using Unmanned Aerial Vehicles.


Exact solution of a jamming transition: closed equations for a bootstrap percolation problem.
Jamming, or dynamical arrest, is a transition at which many particles stop moving in a collective manner. In nature it is brought about by, for example, increasing the packing density, changing the interactions between particles, or otherwise restricting the local motion of the elements of the system. The onset of collectivity occurs because, when one particle is blocked, it may lead to the blocking of a neighbor. That particle may then block one of its neighbors, these effects propagating across some typical domain of size named the dynamical correlation length. When this length diverges, the system becomes immobile. Even where it is finite but large the dynamics is dramatically slowed. Such phenomena lead to glasses, gels, and other very long-lived nonequilibrium solids. The bootstrap percolation models are the simplest examples describing these spatio-temporal correlations. We have been able to solve one such model in two dimensions exactly, exhibiting the precise evolution of the jamming correlations on approach to arrest. We believe that the nature of these correlations and the method we devise to solve the problem are quite general. Both should be of considerable help in further developing this field.


Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.
The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021. The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos. 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure. This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.


A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions.
Some studies suggest that narrow-band imaging (NBI) can be more accurate at diagnosing gastric intestinal metaplasia and dysplasia than white-light endoscopy (WLE) alone. We aimed to assess the real-time diagnostic validity of high resolution endoscopy with and without NBI in the diagnosis of gastric premalignant conditions and to derive a classification for endoscopic grading of gastric intestinal metaplasia (EGGIM). A multicenter prospective study (five centers: Portugal, Italy, Romania, UK, USA) was performed involving the systematic use of high resolution gastroscopes with image registry with and without NBI in a centralized informatics platform (available online). All users used the same NBI classification. Histologic result was considered the diagnostic gold standard. A total of 238 patients and 1123 endoscopic biopsies were included. NBI globally increased diagnostic accuracy by 11 percentage points (NBI 94 % vs. WLE 83 %; P < 0.001) with no difference in the identification of Helicobacter pylori gastritis (73 % vs. 74 %). NBI increased sensitivity for the diagnosis of intestinal metaplasia significantly (87 % vs. 53 %; P < 0.001) and for the diagnosis of dysplasia (92 % vs. 74 %). The added benefit of NBI in terms of diagnostic accuracy was greater in OLGIM III/IV than in OLGIM I/II (25 percentage points vs. 15 percentage points, respectively; P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for EGGIM in the identification of extensive metaplasia was 0.98. In a real-time scenario, NBI demonstrates a high concordance with gastric histology, superior to WLE. Diagnostic accuracy higher than 90 % suggests that routine use of NBI allows targeted instead of random biopsy samples. EGGIM also permits immediate grading of intestinal metaplasia without biopsies and merits further investigation.


Effective Therapy of Drug-Resistant Bacterial Infection by Killing Planktonic Bacteria and Destructing Biofilms with Cationic Photosensitizer Based on Phosphindole Oxide.
Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (β-PM-PIO) is designed and prepared. The unique molecular structure endows β-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. β-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, β-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, β-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.


N719 dye-sensitized organophotocatalysis: enantioselective tandem Michael addition/oxyamination of aldehydes.
A remarkably efficient photosensitizer, N719 dye, was used in asymmetric tandem Michael addition/oxyamination of aldehydes, rendering α,β-substituted aldehydes in good yields with excellent levels of enantioselectivity and diastereoselectivity. This is the first report of a multiorganocatalytic reaction involving iminium catalysis and photoinduced singly occupied molecular orbital (SOMO) catalysis. This reaction is expected to expand the scope of tandem organocatalytic reactions.


The School Environment and Physical and Social-Emotional Well-Being: Implications for Students and School Employees.
The school environment, consisting of the physical environment and social-emotional climate (SEC), plays a crucial role in both student and employee health; however, there is a lack of recent literature synthesizing school environment interventions in K-12 settings. We describe updated evidence about school environment interventions to support K-12 student and employee health in the United States. A 2-phase search included a review of reviews (2010-2018), followed by a search for individual articles (2010-2020) that targeted school physical environment and/or SEC to address physical activity (PA) and/or nutrition. We also investigated how nutrition and PA interventions with an SEC component improves social-emotional and/or mental health outcomes. Because research on dietary and PA behaviors for school employees is limited; we included studies on other worksites (eg, hospitals and offices) to provide insight for school employees. We identified 40 articles describing 40 unique studies and 45 interventions and grouped them by intervention type. Physical environment interventions demonstrated significant and positive nutrition and PA behavioral outcomes for students; outcomes among employees were mixed. Interventions with SEC components reported improvements in some mental health outcomes. The school environment can affect dietary and PA behaviors as well as mental health for students and employees. Establishing healthy school environments can support student and employee PA, dietary behaviors, and mental health.


A herbicide structure-activity analysis of the antimalarial lead compound MMV007978 against Arabidopsis thaliana.
To fight herbicide-resistant weeds, new herbicides are needed; particularly ones with new modes of action. Building on the revelation that many antimalarial drugs are herbicidal, here we focus on the Medicines for Malaria Venture antimalarial lead compound MMV007978 that has herbicidal activity against the model plant Arabidopsis thaliana. Twenty-two variations of the lead compound thiophenyl motif revealed that change was tolerated provided ring size and charge were retained. MMV007978 was active against select monocot and dicot weeds, and physiological profiling indicated that its mode of action is related to germination and cell division. Of interest is the fact that the compound has a profile that is currently not found among known herbicides. We demonstrate that the antimalarial compound MMV007978 is also herbicidal and that exploiting lead compounds that are often understudied could lead to the identification of interesting herbicidal scaffolds. Further structural investigation of MMV007978 could provide improved herbicidal chemistries with a potential new mode of action. © 2018 Society of Chemical Industry.


In Vivo Delivery and Activation of Masked Fluorogenic Hydrolase Substrates by Endogenous Hydrolases in C. elegans.
Protein expression and localization are often studied in vivo by tagging molecules with green fluorescent protein (GFP), yet subtle changes in protein levels are not easily detected. To develop a sensitive in vivo method to amplify fluorescence signals and allow cell-specific quantification of protein abundance changes, we sought to apply an enzyme-activated cellular fluorescence system in vivo by delivering ester-masked fluorophores to Caenorhabditis elegans neurons expressing porcine liver esterase (PLE). To aid uptake into sensory neuron membranes, we synthesized two novel fluorogenic hydrolase substrates with long hydrocarbon tails. Recombinant PLE activated these fluorophores in vitro. In vivo activation occurred in sensory neurons, along with potent activation in intestinal lysosomes quantifiable by imaging and microplate and partially attributable to gut esterase 1 (GES-1) activity. These data demonstrate the promise of biorthogonal hydrolases and their fluorogenic substrates as in vivo neuronal imaging tools and for characterizing endogenous C. elegans hydrolase substrate specificities.


[The characteristics of the blood lipid composition in northern Selkups and in the immigrant population of northern Siberia and the problems of miscegenation].
Blood lipid composition was studied in 507 Selkups, native population of Tyumen Province (199 males and 308 females), 245 Slavs living in the north for more than 5 years (97 males and 148 females), 189 first generation métis born in mixed marriages (68 males and 121 females). Three age groups were analyzed: 10-19 (group 1), 20-39 (group 2), 40-59 (group 3). Male métis from groups 1, 2 and 3 had the highest levels of HDLP cholesterol, the lowest of apoB and atherogenic index. Group 2 métis were in the intermediate position between Slavs and Selkups by concentrations of total and LDLP cholesterol and triglycerides. Group 3 métis males had the lowest levels of triglycerides and intermediate levels of total and LDLP cholesterol. Group 1 and 2 métis females had the highest levels of LDLP, the lowest of apoB and low atherogenic index. In group 3, levels of total cholesterol, LDLP cholesterol, apoB and atherogenic index were as high as in non-aboriginal Slavonic population.


RNA polymerase sliding on DNA can couple the transcription of nearby bacterial operons.
DNA transcription initiates after an RNA polymerase (RNAP) molecule binds to the promoter of a gene. In bacteria, the canonical picture is that RNAP comes from the cytoplasmic pool of freely diffusing RNAP molecules. Recent experiments suggest the possible existence of a separate pool of polymerases, competent for initiation, which freely slide on the DNA after having terminated one round of transcription. Promoter-dependent transcription reinitiation from this pool of posttermination RNAP may lead to coupled initiation at nearby operons, but it is unclear whether this can occur over the distance and timescales needed for it to function widely on a bacterial genome in vivo. Here, we mathematically model the hypothesized reinitiation mechanism as a diffusion-to-capture process and compute the distances over which significant interoperon coupling can occur and the time required. These quantities depend on molecular association and dissociation rate constants between DNA, RNAP, and the transcription initiation factor σ70; we measure these rate constants using single-molecule experiments in vitro. Our combined theory/experimental results demonstrate that efficient coupling can occur at physiologically relevant σ70 concentrations and on timescales appropriate for transcript synthesis. Coupling is efficient over terminator-promoter distances up to ∼1,000 bp, which includes the majority of terminator-promoter nearest neighbor pairs in the Escherichia coli genome. The results suggest a generalized mechanism that couples the transcription of nearby operons and breaks the paradigm that each binding of RNAP to DNA can produce at most one messenger RNA.


Emerging roles of circRNA in formation and progression of cancer.
Circular RNAs (circRNAs) are recently discovered as a special novel type of endogenous noncoding RNAs (ncRNAs), which form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent research revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, as well as interact with RNA-binding proteins (RBPs). In this review, not only the function and mechanism, but also the experimental methods of circRNA are summarized. The summary of the current state of circRNA will help us in the discovery of novel biomarkers, the therapeutic targets and their potential significance in diagnosis and treatment of diseases. CircRNAs might play important roles in cancers especially in hepatocellular carcinoma, gastric carcinoma and colorectal cancer as well as serving as diagnostic or predictive biomarkers of some diseases and providing new treatments of diseases.


(Positive) power to the child: The role of children's willing stance toward parents in developmental cascades from toddler age to early preadolescence.
In a change from the once-dominant view of children as passive in the parent-led process of socialization, children are now seen as active agents who can considerably influence that process. However, these newer perspectives typically focus on the child's antagonistic influence, due either to a difficult temperament or aversive, resistant, negative behaviors that elicit adversarial responses from the parent and lead to future coercive cascades in the relationship. Children's capacity to act as receptive, willing, even enthusiastic, active socialization agents is largely overlooked. Informed by attachment theory and other relational perspectives, we depict children as able to adopt an active willing stance and to exert robust positive influence in the mutually cooperative socialization enterprise. A longitudinal study of 100 community families (mothers, fathers, and children) demonstrates that willing stance (a) is a latent construct, observable in diverse parent-child contexts, parallel at 38, 52, and 67 months and longitudinally stable; (b) originates within an early secure parent-child relationship at 25 months; and (c) promotes a positive future cascade toward adaptive outcomes at age 10. The outcomes include the parent's observed and child-reported positive, responsive behavior, as well as child-reported internal obligation to obey the parent and parent-reported low level of child behavior problems. The construct of willing stance has implications for basic research in typical socialization and in developmental psychopathology as well as for prevention and intervention.


Formation and assessment of a novel surgical video atlas for thyroidectomy.
Within surgery, interactive media have previously been used to educate medical students and residents. Here, we develop and assess the efficacy of a novel surgical video atlas in teaching surgically relevant head and neck anatomy to medical students. A total thyroidectomy was recorded intraoperatively and subsequently narrated to develop a video atlas. Medical students were recruited and randomly assigned to one of the two interventions. One group was assigned to the video atlas, while the other was supplied with a traditional textbook atlas. Both groups underwent pre- and post- tests to evaluate anatomical knowledge and satisfaction. Thirty-seven students completed the study, with 18 students in the experimental group and 19 students as control. In the video atlas arm, mean pre and post-test scores were 57.2% and 84.5%, respectively. In the traditional textbook arm, the mean pre- and post-test scores were 55.3% and 76.51%, respectively. Students with the video atlas had a mean post-test score 8.07% points higher than those without (p = .035). Overall, students were significantly more satisfied with the surgical video atlas than with the standard traditional textbook. A surgical video atlas was shown to more effectively teach head and neck anatomy to medical students compared to standard textbook atlases.


Tumor necrosis factor superfamily in innate immunity and inflammation.
The tumor necrosis factor superfamily (TNFSF) and its corresponding receptor superfamily (TNFRSF) form communication pathways required for developmental, homeostatic, and stimulus-responsive processes in vivo. Although this receptor-ligand system operates between many different cell types and organ systems, many of these proteins play specific roles in immune system function. The TNFSF and TNFRSF proteins lymphotoxins, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes), lymphotoxin-β receptor (LT-βR), and HVEM are used by embryonic and adult innate lymphocytes to promote the development and homeostasis of lymphoid organs. Lymphotoxin-expressing innate-acting B cells construct microenvironments in lymphoid organs that restrict pathogen spread and initiate interferon defenses. Recent results illustrate how the communication networks formed among these cytokines and the coreceptors B and T lymphocyte attenuator (BTLA) and CD160 both inhibit and activate innate lymphoid cells (ILCs), innate γδ T cells, and natural killer (NK) cells. Understanding the role of TNFSF/TNFRSF and interacting proteins in innate cells will likely reveal avenues for future therapeutics for human disease.