Proper Care of Transgender and Gender Diverse Persons in the Setting of Proposed Discrimination: A Policy Perspective.
Transgender and gender diverse (TGD) individuals face significant barriers to accessing health care. Recent introductions of regulatory policies at state and federal levels raise concerns over the politicization of gender-affirming health care, the risks of further restricting access to quality care, and the potential criminalization of healthcare professionals who care for TGD patients. The Endocrine Society and the Pediatric Endocrine Society have published several news articles and comments in the last couple of years supporting safe and effective gender-affirming interventions as outlined in the 2017 Endocrine Society's Clinical Practice Guidelines. The Endocrine Society Position Statement on Transgender Health also acknowledges the rapid expansion in understanding the biological underpinning of gender identity and the need for increased funding to help close gaps in knowledge about the optimal care of TGD individuals. This Policy Perspective affirms these principles in the context of pending and future legislation attempting to discriminate against TGD patients while also stressing the need for science and health care experts to inform health policies.


Connection During COVID-19: Pilot Study of a Telehealth Group Parenting Intervention.
The COVID-19 pandemic has resulted in considerable stress for families, placing parents at risk for heightened psychological distress, while prompting widespread changes in mental health service delivery. This study evaluated treatment engagement, acceptability, and psychiatric distress among participants in the telehealth adaptation of the Connecting and Reflecting Experience (CARE) program after the onset of COVID-19. CARE is a transdiagnostic, bigenerational, mentalizing-focused group parenting intervention based out of an outpatient child mental health clinic in an underserved urban community. Individuals participating in CARE during the clinic's transition to telehealth services were recruited for participation in this pre-post design pilot study. Participants (N=12) completed self-report surveys before and after their first telehealth group session and at their 20-week follow-up. Quantitative and qualitative measures were used to evaluate psychiatric symptoms, treatment engagement, and preliminary acceptability of the adaptation. Self-reported mood and anxiety symptoms decreased significantly after 20 weeks of telehealth therapy. Participants reported high levels of therapeutic alliance and group cohesion in the telehealth format. Results also showed minimal participant-reported privacy concerns and a trend toward increased treatment engagement. These findings have implications regarding the acceptability of teletherapy interventions for caregivers of children during this period of heightened vulnerability and limited access to social support and health services. They also are relevant to establishing the preliminary acceptability of mentalizing-focused parenting inventions delivered via telehealth.


Cardiovascular drift during low intensity exercise with leg blood flow restriction.
Previous studies reported that aerobic-type exercise such as walking or cycling with blood flow restriction (BFR) has been shown to elicit increases in leg muscle hypertrophy and strength, as well as improved aerobic capacity. Although previous studies investigated cardiovascular responses during a relatively short duration of exercise (∼5 min), the effects of prolonged leg muscular BFR have remained unknown. The purpose of this study was to examine the cardiovascular effects of longer duration low intensity exercise combined with BFR. Eight men performed 30 min of exercise at 40% of a predetermined maximal oxygen uptake under both BFR and normal flow (CON) conditions. Cardiovascular parameters were measured at rest and every 10 min during exercise. The main findings were that 1) the SV and HR did not change significantly between 10 to 30 min of exercise in BFR and CON conditions, although BFR-induced reduction of SV and increased HR were found at 10 min exercise compared with normal flow, 2) blood pressure was increased at 10 min of exercise in BFR compared to the CON, however the blood pressure decreased gradually with BFR from 10 to 30 min of exercise, and 3) blood lactate and RPE increased gradually during exercise with BFR. In conclusion, our results suggest that the BFR-induced reduction of SV and increased HR within the first 10 min of exercise are representative of changes in these parameters.


Social connections, trajectories of hopelessness, and serious violence in impoverished urban youth.
Youth living in impoverished urban neighborhoods are at risk for becoming hopeless about their future and engaging in violent behaviors. The current study seeks to examine the longitudinal relationship between social connections, hopelessness trajectories, and subsequent violent behavior across adolescence. Our sample included 723 (49% female) African American youth living in impoverished urban neighborhoods who participated in the Mobile Youth Survey from 1998 through 2006. Using general growth mixture modeling, we found two hopelessness trajectory classes for both boys and girls during middle adolescence: a consistently low hopelessness class and an increasingly hopeless class with quadratic change. In all classes, youth who reported stronger early adolescent connections to their mothers were less hopeless at age 13. The probability of later adolescent violence with a weapon was higher for boys and was associated with the increasingly hopeless class for both boys and girls. Implications for new avenues of research and design of hope-based prevention interventions will be discussed.


Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache?
The time course of propagation of scotoma and blood flow changes during migraine aura parallels the phenomenon of cortical spreading depression (CSD). It was proposed that CSD generates a sterile neurogenic inflammation in the meninges, which may then lead to the activation or sensitization of nociceptors, thus generating headache. We performed rat experiments in which the effect of CSD on plasma extravasation in the dura mater and on neuronal activity in deep laminae of the trigeminal nucleus was assessed in vivo. CSD did not alter dural plasma extravasation measured by means of bovine serum albumin-coupled flourescein (n = 17 rats) compared to the CSD-free contralateral side. In an in vitro model, the application of KCl to the dura at concentrations extracellularly found during CSD did not alter the release of calcitonin gene-related peptide and prostaglandin E2 from the dura. In 33 rats, neither single CSDs nor a series of CSDs altered ongoing neuronal activity or mechanical and/or thermal sensitivity of the deeply located neurons to stimulation of their receptive fields in the dura mater. These results are at variance with data that showed increased c-Fos labeling in superficial laminae of the trigeminal nucleus following CSD. They do not suggest that CSD initiates migraine headache via neurogenic inflammation.


Toward an interdisciplinary approach to understanding sensory function in autism spectrum disorder.
Heightened interest in sensory function in persons with autism spectrum disorder (ASD) presents an unprecedented opportunity for impactful, interdisciplinary work between neuroscientists and clinical practitioners for whom sensory processing is a focus. In spite of this promise, and a number of overlapping perspectives on sensory function in persons with ASD, neuroscientists and clinical practitioners are faced with significant practical barriers to transcending disciplinary silos. These barriers include divergent goals, values, and approaches that shape each discipline, as well as different lexical conventions. This commentary is itself an interdisciplinary effort to describe the shared perspectives, and to conceptualize a framework that may guide future investigation in this area. We summarize progress to date and issue a call for clinical practitioners and neuroscientists to expand cross-disciplinary dialogue and to capitalize on the complementary strengths of each field to unveil the links between neural and behavioral manifestations of sensory differences in persons with ASD. Joining forces to face these challenges in a truly interdisciplinary way will lead to more clinically informed neuroscientific investigation of sensory function, and better translation of those findings to clinical practice. Likewise, a more coordinated effort may shed light not only on how current approaches to treating sensory processing differences affect brain and behavioral responses to sensory stimuli in individuals with ASD, but also on whether such approaches translate to gains in broader characteristics associated with ASD. It is our hope that such interdisciplinary undertakings will ultimately converge to improve assessment and interventions for persons with ASD. Autism Res 2016, 9: 920-925. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.


Assessment of the Quality of Nursing Care From Perspectives of Nurses Who Experienced Hospitalization as Patients.
Nurses as patients or caregivers evaluated their care differently than nonnurses. A qualitative design with content analysis was used to provide an assessment of the quality of nursing care by examining nurses' perceptions as recipients of care. The 231 participants were registered nurses recruited from 8 hospitals in Amman, Jordan. Participants evaluated the quality of nursing care as either high (29.5%) or low (70.5%). Four improvement themes emerged: improving competency, serve with caring, professionalism, and administrative factors.


Kribbella sindirgiensis sp. nov. isolated from soil.
A Kribbella strain FSN23T was isolated from soil sample which was collected from Caygoren Dam lakeside located in Sındırgı, Turkey. The isolate was investigated using a polyphasic approach consisting of numeric, chemotaxonomic and molecular analysis. The isolate indicated chemotaxonomic, morphological and phylogenetic properties associated with members of the genus Kribbella. Phylogenetic analysis based on the 16S rRNA sequence of the strain demonstrated that the strain forms a subclade with K. aluminosa HKI 0478T and K. jejuensis HD9T. The organism formed an extensively branched substrate and aerial hyphae which generated spiral chains of spores with smooth surfaces. The cell wall contained LL-diaminopimelic acid, and the whole cell sugars were glucose and ribose along with trace amounts of mannose. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, four unidentified lipids and five unidentified polar lipids. The predominant menaquinone was MK-9(H4). The major cellular fatty acids were anteiso-C15:0 and iso-C16:0. Polyphasic taxonomy properties confirm that strain FSN23T represents a novel Kribbella taxon distinguished from closely related type strains. Hence, strain FSN23T (=KCTC 29220T = DSM 27082T) is proposed as the type strain of a novel species with the name Kribbella sindirgiensis sp. nov.


Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana.
The genetic basis of seed dormancy, a key life history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions.


[The efficacy of vitrectomy in severe complicated proliferating diabetic retinopathy].
Vitrectomy was made in 69 patients (71 eyes) with proliferative retinopathy complicated by hemorrhage into the vitreous body. In most cases (90.1%), visual acuity didn't exceed 0.05. To prevent possible complications at the time of operation and in the postoperative period preliminary cryocoagulation before vitrectomy was made in a part of the patients (47 patients, 49 eyes). Comparative analysis of results after vitrectomy with and without cryocoagulation has shown that the incidence of operative complications was remarkably lower, than in the first group of patients. Hemorrhage into the vitreous body was observed in combined intervention in 4.0%, and in vitrectomy without preliminary intervention--in 22.7% of cases. Restoration of transparency of the vitreous body was recorded to be more frequent in group I (48.9% against 35.2%). In remote terms, visual acuity improved in 85.7% in group I, and in 45.5%--in group II. Vitrectomy with preliminary cryocoagulation is indicated to all patients with complicated far-advanced proliferative diabetic retinopathy.


Healing of osteotomy sites applying either piezosurgery or two conventional saw blades: a pilot study in rabbits.
The purpose of this study was to compare bone healing of experimental osteotomies applying either piezosurgery or two different oscillating saw blades in a rabbit model. The 16 rabbits were randomly assigned into four groups to comply with observation periods of one, two, three and five weeks. In all animals, four osteotomy lines were performed on the left and right nasal bone using a conventional saw blade, a novel saw blade and piezosurgery. All three osteotomy techniques revealed an advanced gap healing starting after one week. The most pronounced new bone formation took place between two and three weeks, whereby piezoelectric surgery revealed a tendency to faster bone formation and remodelling. Yet, there were no significant differences between the three modalities. The use of a novel as well as the piezoelectric bone-cutting instrument revealed advanced bone healing with a favourable surgical performance compared to a traditional saw.


Status, evaluation, and influencing factors of biosecurity levels in pig farms in China.
Animal diseases have always been a serious threat to livestock breeding, and the establishment of a biosecurity barrier is important for disease prevention and control. Based on the investigations conducted in seven provinces located farms, this study aimed to explore the current biosecurity levels of farms in China, construct a biosecurity evaluation system, calculate the biosecurity levels of farms using the rank sum ratio comprehensive evaluation method, and develop an empirical analysis of the factors influencing biosecurity levels. The results show that the greater the cost of biosecurity invested, the greater the level of biosecurity. Male farmers, educational attainment and participation in technical training had a significant positive effect on biosecurity levels. In addition, biosecurity levels first decreased and then increased as the scale of farming increased. The study also found that the more people in the household engaged in farming, the higher the biosecurity level of the farm. And farms that joined cooperatives had higher levels of biosecurity. The rank sum ratio method can evaluate the index system, so as to obtain a comprehensive index RSR value that can be compared, and the operation steps are simple and effective. By taking measures such as improving the comprehensive quality of farmers and increasing the investment in human, material and financial resources for biosecurity, the biosecurity level of farms can be effectively improved and animal diseases can be effectively prevented and controlled.


Antitumor activity of the 3'-chloroethylnitrosourea analog of thymidine and the prevention by co-administered thymidine of lethality but not of anticancer activity.
The effect of the 3'-nitrosourea analog of thymidine (3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine; 3'-CTNU) on the growth of the murine L1210 and P388 leukemias in mice was investigated. A single injection of 3'-CTNU (40 mg/kg) was minimally toxic to mice bearing the L1210 leukemia and produced 60-day survivors. The coadministration of thymidine did not prevent the initial loss of weight caused by 3'-CTNU but did prevent the lethality otherwise produced in non-tumor-bearing mice. A single dose of thymidine (2 g/kg) administered to L1210-bearing mice had no anticancer activity and when coadministered with 3'-CTNU had no detrimental effect on the potent antitumor effects of 3'-CTNU. Similar results were obtained against P388 leukemia. The hematopoietic toxicity produced by the administration of 3'-CTNU to non-tumor-bearing mice, as evidenced by changes in the white blood cells, neutrophil, and agar diffusion chamber precursor cell concentrations in the hematocrit and in bone marrow cellularity, could not be prevented by thymidine. Therefore, the lethality produced by 3'-CTNU is probably not related to hematopoietic toxicity since the coadministration of thymidine completely prevented any lethality.


Long acting beta-agonists versus theophylline for maintenance treatment of asthma.
Theophylline and long acting beta2-agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. To assess the comparative efficacy, safety and side-effects of long-acting beta-agonists and theophylline in the maintenance treatment of asthma. Randomised, controlled trials (RCTs) were identified using the Cochrane Airways Group register. The register was searched using the following terms: asthma and theophylline and long acting beta-agonist or formoterol or foradile or eformoterol or salmeterol or bambuterol or bitolterol. Titles and abstracts were then screened to identify potentially relevant studies. The bibliography of each RCT was searched for additional RCTs. Authors of identified RCTs were contacted for other relevant published and unpublished studies. All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-agonist. Potentially relevant trials, identified by screening titles and/or abstracts, were obtained. Two reviewers independently assessed full text versions of these trials to decided whether the trial should be included in the review, and assessed its methodological quality. Where there was disagreement between reviewers, this was resolved by consensus, or reference to a third party. Data were extracted by two independent reviewers. Inter-rater reliability was assessed by simple agreement. Study authors were contacted to clarify randomisation methods, provide missing data, verify the data extracted and identify unpublished studies. Relevant pharmaceutical manufacturers were also contacted. Six trials met the inclusion criteria. Five used salmeterol and one, biltoterol. They were of varying quality. There was a trend for salmeterol to improve FEV1 more than theophylline in three studies and salmeterol use was associated with more symptom free nights. Bitolterol, used in only one study, was reported to be less effective than theophylline. Subjects taking salmeterol experienced fewer adverse events than those using theophylline (Relative Risk 0.38; 95%Confidence Intervals 0.25, 0.57). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.51; 95%Confidence Intervals 0.30, 0.88) and gastrointestinal adverse events (Relative Risk 0.32; 95%Confidence Intervals 0.17, 0.59). Salmeterol may be more effective than theophylline in reducing asthma symptoms including night waking and improving lung function. More adverse events occurred in subjects using theophylline when compared to salmeterol.


Candidate Modifier Genes for the Penetrance of Leber's Hereditary Optic Neuropathy.
Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation. It is characterized by acute and subacute visual loss predominantly affecting young men. The mtDNA mutation is transmitted to all maternal lineages. However, only approximately 50% of men and 10% of women harboring a pathogenic mtDNA mutation develop optic neuropathy, reflecting both the incomplete penetrance and its unexplained male prevalence, where over 80% of patients are male. Nuclear modifier genes have been presumed to affect the penetrance of LHON. With conventional genetic methods, prior studies have failed to solve the underlying pathogenesis. Whole exome sequencing (WES) is a new molecular technique for sequencing the protein-coding region of all genes in a whole genome. We performed WES from five families with 17 members. These samples were divided into the proband group (probands with acute onset of LHON, n = 7) and control group (carriers including mother and relative carriers with mtDNSA 11778 mutation, without clinical manifestation of LHON, n = 10). Through whole exome analysis, we found that many mitochondria related (MT-related) nuclear genes have high percentage of variants in either the proband group or control group. The MT genes with a difference over 0.3 of mutation percentage between the proband and control groups include AK4, NSUN4, RDH13, COQ3, and FAHD1. In addition, the pathway analysis revealed that these genes were associated with cofactor metabolism pathways. Family-based analysis showed that several candidate MT genes including METAP1D (c.41G > T), ACACB (c.1029del), ME3 (c.972G > C), NIPSNAP3B (c.280G > C, c.476C > G), and NSUN4 (c.4A > G) were involved in the penetrance of LHON. A GWAS (genome wide association study) was performed, which found that ADGRG5 (Chr16:575620A:G), POLE4 (Chr2:7495872T:G), ERMAP (Chr1:4283044A:G), PIGR (Chr1:2069357C:T;2069358G:A), CDC42BPB (Chr14:102949A:G), PROK1 (Chr1:1104562A:G), BCAN (Chr 1:1566582C:T), and NES (Chr1:1566698A:G,1566705T:C, 1566707T:C) may be involved. The incomplete penetrance and male prevalence are still the major unexplained issues in LHON. Through whole exome analysis, we found several MT genes with a high percentage of variants were involved in a family-based analysis. Pathway analysis suggested a difference in the mutation burden of MT genes underlining the biosynthesis and metabolism pathways. In addition, the GWAS analysis also revealed several candidate nuclear modifier genes. The new technology of WES contributes to provide a highly efficient candidate gene screening function in molecular genetics.


Continuous Renal Replacement Therapy in Venovenous Extracorporeal Membrane Oxygenation: A Retrospective Study on Regional Citrate Anticoagulation.
Systemic infusion of unfractionated heparin (UFH) is the standard anticoagulation technique for continuous renal replacement therapy (CRRT) during extracorporeal membrane oxygenation (ECMO), but often fails to avoid CRRT circuit clotting. The aim of this study was to assess, in patients undergoing CRRT during venovenous ECMO (vv-ECMO), the efficacy and safety of adding regional citrate anticoagulation (RCA) for CRRT circuit anticoagulation (RCA + UFH group) compared with the sole systemic heparin anticoagulation (UFH group). We performed a retrospective chart review (2009-2018) of patients treated with CRRT during ECMO. We evaluated filter life span, rate of CRRT circuit clotting, and coagulation parameters. The incidence of citrate anticoagulation-related complications was recorded. Forty-eight consecutive adult patients underwent CRRT during vv-ECMO in the study period. The incidence of CRRT circuit clotting was lower in the RCA + UFH group (11% vs. 38% in the UFH group, p < 0.001). Log-rank survival analysis demonstrated longer circuit lifetime for RCA + UFH group. No complication ascribable to citrate anticoagulation was recorded. Regional citrate anticoagulation resulted a feasible, safe, and effective technique as additional anticoagulation for CRRT circuits during ECMO. Compared with systemic heparinization only, this technique allowed to reduce the rate of CRRT circuit clotting.


Land-use change promotes avian diversity at the expense of species with unique traits.
Land-use change may alter both species diversity and species functional diversity patterns. To test the idea that species diversity and functional diversity changes respond in differing ways to land-use changes, we characterize the form of the change in bird assemblages and species functional traits along an intensifying gradient of land use in the savanna biome in a historically homogeneous vegetation type in Phalaborwa, South Africa. A section of this vegetation type has been untransformed, and the remainder is now mainly characterized by urban and subsistence agricultural areas. Using morphometric, foraging and breeding functional traits of birds, we estimate functional diversity changes. Bird species richness and abundance are generally higher in urban and subsistence agricultural land uses, as well as in the habitat matrix connecting these regions, than in the untransformed area, a pattern mainly driven through species replacement. Functionally unique species, particularly ground nesters of large body size, were, however, less abundant in more utilized land uses. For a previously homogenous vegetation type, declines in the seasonality of energy availability under land-use change have led to an increase in local avian diversity, promoting the turnover of species, but reduced the abundance of functionally unique species. Although there is no simple relationship between land-use and diversity change, land-use change may suit some species, but such change may also involve functional homogenization.


Co-occurrence of diabetes and hypertension: pattern and factors associated with order of diagnosis among nigerians.
There is a high frequency of co-occurrence of diabetes and hypertension all over the world. Such association results in higher rate of cardiovascular complications. It is however not clear whether the order of occurrence distinguishes two different groups of patients and the implications of this on morbidity and mortality. The main objective of this study is to determine if there are any clinical and metabolic differences between those first diagnosed with diabetes (hypertensive diabetics) compared to those first diagnosed with hypertension (diabetic hypertensives). A total of 124 patients with co-existent diabetes and hypertension were consecutively recruited into the study. Demographic and clinical history was captured on a semi-structured questionnaire, followed by measurement of anthropometry and blood pressure. Records of fasting plasma glucose, urinalysis and electrolytes, urea and creatinine were obtained from the case records. There were 83 (66.9%) females and 41 (33.1%) males with mean age of 61.1 (SD 11.1) years. Sixty or 49.6% was hypertensive diabetics while 52 or 43% was diabetic hypertensive. The rest had simultaneous diagnosis of diabetes and hypertension. The diabetic hypertensive subjects significantly had higher BMI (p= 0.04) while the hypertensive diabetics group had higher hip/waist ratio (p = 0.01). The diabetic hypertensive group had higher waist circumference statistically significant only in women (p = 0.04). Also significantly more people (21 or 42%; p = 0.04) in the diabetic hypertensive group used table salt often. A logistic regression performed showed that only use of table salt was independently associated with order of diagnosis of diabetes or hypertension. There could be significant differences in some clinical characteristics of hypertensive diabetics and diabetic hypertensives, and use of table salt may be an important risk factor contributing to coexistence of both conditions.


Serum diagnosis of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass spectrometry.
Each year in the United States, approximately 30,000 people die from pancreatic cancer. Fewer than 5% of patients survive >5 years after diagnosis, because most patients present with advanced disease. Early diagnosis may improve the prognosis of patients with pancreatic cancer. In an attempt to improve on current approaches to the serological diagnosis of pancreatic cancer, we analyzed serum samples from patients with and without pancreatic cancer using surface-enhanced laser desorption and ionization (SELDI) protein chip mass spectrometry. Using a case-control study design, serum samples from 60 patients with resectable pancreatic adenocarcinoma were compared with samples from 60 age- and sex-matched patients with nonmalignant pancreatic diseases, as well as 60 age- and sex-matched healthy controls. To increase the number of proteins potentially identifiable, serum was fractionated using anion exchange and profiled on two ProteinChip surfaces (metal affinity capture and weak cation exchange). We determined a minimum set of protein peaks able to discriminate between patient groups and used the unified maximum separability algorithm to compare the performance of the individual marker panels alone or in conjunction with CA19-9. Among the peaks identified by SELDI profiling that had the ability to distinguish between patient groups, the 2 most discriminating protein peaks could differentiate patients with pancreatic cancer from healthy controls with a sensitivity of 78% and specificity of 97%. These 2 markers performed significantly better than the current standard serum marker, CA19-9 (P < 0.05). The diagnostic accuracy of the 2 markers was improved by using them in combination with CA 19-9. Similarly, a combination of 3 SELDI markers and CA19-9 was superior to CA19-9 alone in distinguishing individuals with pancreatic cancer from the combined pancreatic disease controls and healthy subject groups (P = 0.078). SELDI markers were also better than CA19-9 in distinguishing patients with pancreatic cancer from those with pancreatitis. SELDI profiling of serum can be used to accurately differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy controls.


Workload and sources of remuneration for radiologists at a tertiary-care teaching hospital in Ontario.
Detailed information about workload and sources of remuneration for radiologists at a large tertiary-care teaching hospital was reviewed for the calendar year 1991 as part of an assessment of medical professional resources. Radiologists at this facility worked an average of about 50 hours per week. When the intensity of the cases was taken into consideration, there was only a small variation among individual radiologists in terms of workload and income earned for the group. Ninety-three percent of the radiologists' remuneration came as payment for clinical patient care. The radiologists were poorly remunerated for the time they spent teaching, conducting research and performing administrative duties, but this low level of remuneration was partially compensated by the activity of senior residents, who did some work without supervision.


Microtubule-dependent microtubule nucleation based on recruitment of gamma-tubulin in higher plants.
Despite the absence of a conspicuous microtubule-organizing centre, microtubules in plant cells at interphase are present in the cell cortex as a well oriented array. A recent report suggests that microtubule nucleation sites for the array are capable of associating with and dissociating from the cortex. Here, we show that nucleation requires extant cortical microtubules, onto which cytosolic gamma-tubulin is recruited. In both living cells and the cell-free system, microtubules are nucleated as branches on the extant cortical microtubules. The branch points contain gamma-tubulin, which is abundant in the cytoplasm, and microtubule nucleation in the cell-free system is prevented by inhibiting gamma-tubulin function with a specific antibody. When isolated plasma membrane with microtubules is exposed to purified neuro-tubulin, no microtubules are nucleated. However, when the membrane is exposed to a cytosolic extract, gamma-tubulin binds microtubules on the membrane, and after a subsequent incubation in neuro-tubulin, microtubules are nucleated on the pre-existing microtubules. We propose that a cytoplasmic gamma-tubulin complex shuttles between the cytoplasm and the side of a cortical microtubule, and has nucleation activity only when bound to the microtubule.


Deciphering Deoxynybomycin Biosynthesis Reveals Fe(II)/α-Ketoglutarate-Dependent Dioxygenase-Catalyzed Oxazoline Ring Formation and Decomposition.
The antibacterial agents deoxynybomycin (DNM) and nybomycin (NM) have a unique tetracyclic structure featuring an angularly fused 4-oxazoline ring. Here, we report the identification of key enzymes responsible for forming the 4-oxazoline ring in Embleya hyalina NBRC 13850 by comparative bioinformatics analysis of the biosynthetic gene clusters encoding structurally similar natural products DNM, deoxynyboquinone (DNQ), and diazaquinomycins (DAQs). The N-methyltransferase DnmS plays a crucial role in catalyzing the N-dimethylation of a tricyclic precursor prenybomycin to generate NM D; subsequently, the Fe(II)/α-ketoglutarate-dependent dioxygenase (Fe/αKGD) DnmT catalyzes the formation of a 4-oxazoline ring from NM D to produce DNM; finally, a second Fe/αKGD DnmU catalyzes the C-12 hydroxylation of DNM to yield NM. Strikingly, DnmT is shown to display unexpected functions to also catalyze the decomposition of the 4-oxazoline ring and the N-demethylation, thereby converting DNM back to prenybomycin, to putatively serve as a manner to control the intracellular yield of DNM. Structure modeling, site-directed mutagenesis, and quantum mechanics calculations provide mechanistic insights into the DnmT-catalyzed reactions. This work expands our understanding of the functional diversity of Fe/αKGDs in natural product biosynthesis.


Effect of knee joint cooling on the electromyographic activity of lower extremity muscles during a plyometric exercise.
During sporting events, injured athletes often return to competition after icing because of the reduction in pain. Although some controversy exists, several studies suggest that cryotherapy causes a decrease in muscle activity, which may lead to a higher risk of injury upon return to play. The purpose of this study was to investigate the effect of a 20-min knee joint cryotherapy application on the electromyographic activity of leg muscles during a single-leg drop jump in twenty healthy subjects, randomly assigned to an experimental and a control group. After the pre-tests, a crushed-ice bag was applied to the knee joint of the experimental group subjects for 20 min, while the control group subjects rested for 20 min. All subjects were retested immediately after this period and retested again after another 20 min of rest. Average electromyographic activity and ground contact time were calculated for the pre- and post-test sessions. Decreases in electromyographic activity of the lower extremity musculature were found in pre-activation, eccentric (braking), and concentric (push-off) phases immediately after the icing, and after 20 min of rest. The results lend support to the suggestion that cryotherapy during sporting events may place the individuals in a vulnerable position.


[Cefuroxime-tobramycin treatment of bacterial infections in cancer patients].
Twenty-five patients with different metastatic tumors, and often with other diseases which may have further compromised their defenses (such as diabetes, anemia and neutropenia), had a simultaneous bacterial complication. This was regarded as documented (i.e., proved by positive culture) in 12 of 25 patients, and probable if subjective and objective symptoms, X-ray, laboratory tests and the clinical picture agreed with bacterial infection in progress, even though the culture was negative, in 13 of 25 patients. Antibiotic therapy with cefuroxime-tobramycin gave good results in 19 of 25 patients, i.e., in 10 of 12 with a documented infection and in 9 of 13 with a probable infection. Fever of unknown origin and urinary infections were the most responsive to the therapy. Three of 25 patients had nephrotoxicity, with a very small rise in BUN and creatinine, which was easily reversible. According to our experience, antibiotic therapy with cefuroxime-tobramycin would be useful in cancer patients with bacterial complications because of its effectiveness and tolerability.


Pacing mode and long-term survival in elderly patients with congestive heart failure: 1980-1985.
Dual-chamber pacing may improve short-term hemodynamics and functional class in some patients with congestive heart failure, even in the absence of conventional indications for pacemaker implantation. However, the impact of different pacing modes on survival of patients with congestive heart failure is controversial. In this retrospective study we analyzed survival data from 546 elderly patients, aged 70 years and older, who underwent implantation of a permanent dual-chamber (DDD, n = 62, DVI, n = 102) or single-chamber (VVI) pacemaker (n = 382) between 1980 and 1985. Survival was further analyzed according to the presence of absence of congestive heart failure, and pacemaker mode (DDD vs. DVI vs. VVI). Overall, dual-chamber pacing (DDD and DVI) was associated with a more favorable long-term outcome when compared with single-chamber ventricular pacing, although differences were only significant for DDD pacing (P = 0.002). When patients with and without preexisting congestive heart failure were analyzed separately, survival following dual-chamber pacing (DDD and DVI) was significantly better than survival following single-chamber pacing in patients without congestive heart failure (P = 0.03), but not in patients with preexisting heart failure (P = 0.139). When patients were analyzed according to the electrophysiological indication for pacemaker implantation, overall survival of patients with AV block (P = 0.0025) but not sinus node dysfunction (P = 0.346) was improved with dual-chamber pacing. This survival advantage in patients with AV block following dual-chamber pacing was lost in the presence of heart failure (P = 0.11). These findings suggest that dual-chamber pacing, in particular DDD pacing, improves the survival in elderly patients without preexisting congestive heart failure. In contrast to the short-term hemodynamic improvement observed in selected patients with congestive heart failure, dual-chamber pacing in elderly patients with congestive heart failure, paced for conventional indications, is not associated with improved survival when compared with single-chamber ventricular pacing.


Dorsal horn (convergent) neurones in the intact anaesthetized arthritic rat. II. Heterotopic inhibitory influences.
Recordings were made from dorsal horn neurones in the spinal cord and trigeminal nucleus caudalis of intact anaesthetized rats. These rats had been rendered polyarthritic by s.c. injection of Mycobacterium butyricum suspended in oil into the base of the tail. The experiments were carried out during the acute phase of the illness (3-4 weeks post inoculation) during which hyperalgesia occurred. The disease mainly affected the hind paws and the tail and, to a lesser extent, the forepaws. The facial area of the animals was not at all affected. As described in a previous paper, recordings from lumbar dorsal horn neurones revealed that two subpopulations could be described on the basis of their electrophysiological characteristics. Namely, 'typical' units which include convergent, non-noxious and proprioceptive neurones and which have properties essentially similar to those found in healthy rats, and 'atypical' cells which have no counterpart in healthy rats and which include convergent and non-noxious neurones. All the typical convergent neurones were inhibited by noxious stimuli applied to heterotopic body areas, whereas typical non-noxious and proprioceptive neurones were not; these observations are similar to those described in healthy rats as diffuse noxious inhibitory controls (DNIC). However, it was also found that 88% of the atypical convergent and 85% of the atypical non-noxious cells were inhibited by various heterotopic stimuli. The most important observation was that gentle stimulation such as mild pressure applied to the inflamed contralateral ankle joint--a stimulus intensity which has never been found to be effective in healthy animals--was capable of triggering inhibition of both typical and atypical convergent neurones. Recordings from trigeminal nucleus caudalis neurones revealed that the entire population presented essentially the same properties as those observed in healthy animals in terms of activity evoked by natural or electrical stimulation of their excitatory receptive fields. The activity of non-noxious neurones was never modified by any heterotopically applied stimuli. By contrast, all convergent neurones were inhibited by heterotopic stimuli, noxious (52 degrees C, pinch) or non-noxious (light and mild pressure), applied to inflamed areas. While the inhibition triggered by noxious stimuli was reminiscent of that observed in healthy rats, the inhibition triggered by non-noxious mechanical stimuli was related to the inflammatory state of the part of the body stimulated, the most sensitive areas being the hind paws.(ABSTRACT TRUNCATED AT 400 WORDS)


Determination of mechanical and electronic shifts for pinhole SPECT using a single point source.
The effects of uncompensated electronic and mechanical shifts may compromise the resolution of pinhole single photon emission computed tomography. The resolution degradation due to uncompensated shifts is estimated through simulated data. A method for determining the transverse mechanical and axial electronic shifts is described and evaluated. This method assumes that the tilt of the detector and the radius of rotation (ROR) are previously determined using another method. When this assumption is made, it is possible to determine the rest of the calibration parameters using a single point source. A method that determines the electronic and mechanical shifts as well as the tilt has been previously described; this method requires three point sources. It may be reasonable in most circumstances to calibrate tilt much less frequently than the mechanical shifts since the tilt is a property of the scanner whereas the mechanical shift may change every time the collimator is replaced. An alternative method for determining the ROR may also be used. Lastly, we take the view that the transverse electronic shift and the focal length change slowly and find these parameters independently.


The diagnostic value of D-dimer, procalcitonin and CRP in acute appendicitis.
The early diagnosis of acute abdomen is of great importance. To date, several inflammatory markers have been used for the diagnosis of acute abdominal conditions, including acute appendicitis. The aim of this study was to evaluate the diagnostic utility of D-dimer, Procalcitonin (PCT) and C-reactive protein (CRP) measurements in the acute appendicitis. This prospective study was conducted between March 1(st), 2010 and July 1(st), 2011. In this period, seventy-eight patients were operated with the diagnosis of acute appendicitis, and D-dimer, PCT and CRP levels of the patients were measured. The patients were grouped as phlegmonous appendicitis (Group 1), gangrenous appendicitis (Group 2), perforated appendicitis (Group 3) and negative appendectomy (Group 4) according to the surgical findings and histopathological results. Of 78 patients, 54 (69.2 %) were male and 24 (30.8 %) were female, and the mean age was 25.4 ± 11.1 years (range, 18 to 69 years). 66 (84.6 %) patients had increased leukocyte count (white blood cell count). The PCT values were higher than the upper normal limit in 20 (25.6%) patients, followed by D-dimer in 22 (28.2 %) patients and CRP in 54 (69.2 %) patients. The diagnostic value of leukocyte count and CRP in acute appendicitis was higher than that of the other markers, whereas leukocyte count showed very low specificity. CRP values were higher in perforated appendicitis when compared with the phlegmonous appendicitis (p < 0.05). However, PCT and D-dimer showed lower diagnostic values (26% and 31%, respectively). An increase in CRP levels alone is not sufficient to make the diagnosis of acute appendicitis. However, CRP levels may differentiate between phlegmonous appendicitis and perforated appendicitis. Due to their low sensitivity and diagnostic value, PCT and D-dimer are not better markers than CRP for the diagnosis of acute appendicitis.


Knowledge and Attitude among General Dental Practitioners towards Minimally Invasive Dentistry in Riyadh and AlKharj.
Minimally Invasive Dentistry (MID) emphasizes conservative caries management strategies resulting in less destruction of tooth structure, a deviation of the traditional GV Black's restorative principles. However, there seems to be either deficiency in knowledge or little intention by general dental practitioners to adopt these principles. The aim of this study was to assess the knowledge and attitude among general dental practitioners towards minimally invasive dentistry in Riyadh and AlKharj cities of Saudi Arabia. Self-administered structured questionnaires were handed to general dental practitioners (GDPs) in the cities of Riyadh and AlKharj in Saudi Arabia. Several questions, including Likert-type scale response categories (1-5), were used. The questions assessed the respondents' levels of agreement regarding diagnostic, preventive and restorative techniques such as use of caries risk assessment, use of high fluoride tooth paste, Atraumatic Restorative Treatment and tunnel preparations. Out of 200 respondents, 161 GDPs with overall response rate of 80.5% completed the questionnaires. The GDPs showed significantly different approach with regards to the use of sharp explorer for caries detection (p = 0.014). Almost 60% of the participants had received no special education regarding minimally invasive procedures. Moreover, GDPs who had received MID training showed significantly better knowledge and attitude in adopting minimally invasive techniques for both diagnosis and treatment of dental caries. Although GDPs possess knowledge about the benefits of MID; however, study showed deficiencies in their attitudes towards caries detection methods and application of minimally invasive dentistry procedures.


Comparison of fluorescent BACTEC 9000 MB system, Septi-Chek AFB system, and Lowenstein-Jensen medium for detection of mycobacteria.
The newly developed fluorescent BACTEC 9000 MB system for automated culture of mycobacteria was compared with the Septi-Chek AFB system and Lowenstein-Jensen medium (LJ). A total of 2,005 clinical specimens were included in the study. Mycobacteria were isolated from 202 (10.1%) specimens, including 155 Mycobacterium tuberculosis complex isolates and 47 Mycobacteria other than M. tuberculosis isolates. Of 131 isolates detected by the BACTEC system, the Septi-Chek AFB system, or both, 120 (91.6%) were detected by the BACTEC system and 105 (80.2%) were detected by the Septi-Chek AFB system (P < 0.02). The recovery rate in the BACTEC system compared with that in the Septi-Chek AFB system was significantly higher for M. tuberculosis complex isolates (P < 0.005) and for isolates from acid-fast smear-negative specimens (P < 0.01). Of 148 isolates detected by the BACTEC system, LJ, or both, 142 (95.9%) were detected by the BACTEC system and 118 (79.9%) were detected by LJ (P < 0.001). The recovery rate in the BACTEC system compared with that on LJ was significantly higher for M. tuberculosis complex isolates (P < 0.001). The BACTEC system detected more mycobacteria from both smear-positive and smear-negative specimens than LJ. The mean times to detection of mycobacteria were 17.6 days for the BACTEC system, 26.0 days for the Septi-Chek AFB system, and 29.4 days for LJ. The BACTEC fluorescent 9000 MB system is a rapid, sensitive, and efficient method for the isolation of mycobacteria.


Exploring Biomarkers for Alzheimer's Disease.
Alzheimer's Disease (AD) is one of the most common form of dementia occurring in elderly population worldwide. Currently Aβ42, tau and p-tau in the cerebrospinal fluid is estimated for confirmation of AD. CSF which is being used as the potent source for biomarker screening is obtained by invasive lumbar punctures. Thus, there is an urgent need of minimal invasive methods for identification of diagnostic markers for early detection of AD. Blood serum and plasma serves as an appropriate source, due to minimal discomfort to the patients, promoting frequent testing, better follow-up and better consent to clinical trials. Hence, the need of the hour demands discovery of diagnostic and prognostic patient specific signature biomarkers by using emerging technologies of mass spectrometry, microarrays and peptidomics. In this review we summarize the present scenario of AD biomarkers such as circulatory biomarkers, blood based amyloid markers, inflammatory markers and oxidative stress markers being investigated and also some of the potent biomarkers which might be able to predict early onset of Alzheimer's and delay cognitive impairment.


Diesel Exhaust Exposure Assessment Among Tunnel Construction Workers-Correlations Between Nitrogen Dioxide, Respirable Elemental Carbon, and Particle Number.
Occupational exposure to diesel exhaust is common due the widespread use of diesel-powered combustion engines. Diesel exhaust is chemically complex and consists of thousands of compounds present as gases and particulate matter. Both nitrogen dioxide (NO2) and elemental carbon (EC) have been used as markers for diesel exhaust exposure. Currently EC is regarded as the best surrogate of diesel exhaust. The objective was to quantify the occupational exposure to diesel exhaust in underground tunnel construction work using a multi-metric approach, and to investigate the correlations between NO2, respirable EC, respirable organic carbon (OC), respirable total carbon (TC), respirable dust (RD), and particle number. Also, the use of NO2 as a proxy for diesel exhaust was evaluated, how much of the variability in the diesel exhaust exposure was attributed to within and between individual factors and if there was a difference between expert and self-administered measurements of NO2. The personal exposure to diesel exhaust was assessed by expert supervised measurements of NO2, EC, OC, TC, RD and particle number in the breathing zones of underground tunnel workers. Stationary sampling of NO2, EC, OC, TC, RD, size-fractioned mass concentration, and particle number were conducted. The personal and stationary measurements were conducted on three occasions simultaneously. The workers measured their exposure by repeated self-administered measurements of NO2. The self-administered measurements were performed twice for each worker with at least one month lag between the samplings. In the simultaneous sampling of diesel exhaust, the geometric mean (GM) concentration of NO2 and respirable EC were 72 µg m-3 (10th-90th percentile 34-140 µg m-3) and 2.6 µg m-3 (10th-90th percentile 1.6-7.3 µg m-3), respectively. The GM for OC and TC was 28 µg m-3 (10th-90th percentile 20-42 µg m-3) and 31 µg m-3 (10th-90th percentile 20-50 µg m-3), respectively. The GM for RD and particle number was 180 µg m-3 (10th-90th percentile 20-530 µg m-3) and 47 900 cm-3 (10th-90th percentile 27500-94100 cm-3), respectively. A significant correlation was found between NO2 and respirable EC [Spearman's correlation r = 0.53 (P = 0.05)]. The within-worker variability of NO2 was 45.5% and the between-worker variability was 54.5%. The self-administered measured concentrations of NO2 (GM 70 µg m-3) did not statistically differ from the NO2 concentrations measured by an expert (P > 0.35). The diesel exhaust exposure in tunnel construction work was low. A significant correlation between NO2 and EC was observed. This indicates that NO2 could be used as a proxy for diesel exhaust in tunnel work if diesel exhaust is the only source of NO2 and if the ratio between EC and NO2 is known and constant. Passive sampling of NO2 is much easier and cheaper to perform compared with active sampling of EC. It is possible to utilize self-administered NO2 measurements in extreme and inaccessible work environments. This study adds support to continued use of NO2 as an exposure marker in combination with EC for diesel exhaust exposure. In tunnel construction work, the variability in the diesel exhaust exposure was high both between- and within-workers.


Maryland's Integration of Public Health and Primary Care During the COVID-19 Pandemic: Case Study and Lessons Learned.
The Maryland Primary Care Program is a statewide advanced primary care program that works directly with practices to transform healthcare delivery by managing chronic disease, preventing unnecessary hospital utilization, and integrating with the public health system. The Maryland Primary Care Program has demonstrated how linking the public health system to primary care practices, paired with strategic financial and resource investments in primary care, can enable the delivery of high-value care and reduce acute hospital utilization. Such a system is especially prudent when responding to crises. Throughout the COVID-19 pandemic, the Maryland Primary Care Program was able to capitalize on existing infrastructure to quickly engage primary care in a robust pandemic response. Successes of this relationship included early and consistent communication channels, as well as coordinated resource distribution. In particular, this partnership allowed primary care providers, the most trusted source of healthcare in patients' lives, to directly provide patients with health information and vaccines. Now comprising more than 500 practices, this vaccine program uses data-driven reports to facilitate intentional vaccine outreach. The program has enabled a more equitable vaccine distribution system, resulting in over 400,000 vaccines administered in Maryland counties. The effectiveness of Maryland's integrated response indicates that partnerships between public health and primary care will result in an effective response in future times of crisis.


Messenger RNA complexity in Drosophila melanogaster.
Complementary DNA was synthesized as a copy of polyadenylated RNA from the cytoplasm of Drosophila cultured cells. The kinetics of hybridization of cDNA with the RNA used as template revealed a complex distribution of frequencies in the population of polyadenylated RNA. Computer simulation suggested three frequency classes containing about 4, 190, and 6700 different RNA molecules of mean molecular weight 4 x 10-5. About 15% of this complementary DNA reacted with repetitive sequences of Drosophila DNA. The most frequent polyadenylated RNA is preferentially enriched in its content of repetitive sequences. Comparative experiments using cDNA synthesized as a complement of larval polyadenylated RNA demonstrated some stage specific changes in the population of polyadenylated RNA.


Toxic megacolon complicating a first course of Crohn's disease: about two cases.
Toxic megacolon is a rare and serious complication of Crohn's disease. Because of the associated high morbidity and mortality, early recognition and management of toxic megacolon is important. Through two cases of toxic megacolon complicating Crohn's disease, we assessed the clinical, radiologic and therapeutic characteristics of this complication. A 35-year-old man presented a first course of Crohn's disease treated with corticosteroid. He exhibited sudden severe abdominal pain and distension with shock. A plain abdominal radiography revealed toxic megacolon. He underwent medical therapy, but symptoms not relieved. The patient underwent subtotal colectomy with ileostomy. The resected specimen confirmed the diagnosis. Recovery of digestive continuity was performed. Endoscopic evaluation six months later did not shown recurrence. A 57-year-old man presented with severe acute colitis inaugurating Crohn's disease, was treated with corticosteroid and antibiotics. He exhibited signs of general peritonitis. Computed tomographic examination revealed toxic megacolon with free perforation, showing prominent dilation of the transverse colon and linear pneumatosis. The patient underwent emergent subtotal colectomy and ileostomy. The final histological patterns were consisting with diagnosis of Crohn's disease associated with cytomegalovirus infection. The patient underwent antiviral therapy during 15 days. Because of the high risk of postoperative recurrence, he underwent immunosuppressive therapy. Recovery of digestive continuity was performed successfully. Toxic megacolon in Crohn's disease is a serious turning of this disease. We underscore the importance of early diagnosis of toxic megacolon and rapid surgical intervention if improvement is not observed on medical therapy.


The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.
Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.


The kinase inhibitor SFV785 dislocates dengue virus envelope protein from the replication complex and blocks virus assembly.
Dengue virus (DENV) is the etiologic agent for dengue fever, for which there is no approved vaccine or specific anti-viral drug. As a remedy for this, we explored the use of compounds that interfere with the action of required host factors and describe here the characterization of a kinase inhibitor (SFV785), which has selective effects on NTRK1 and MAPKAPK5 kinase activity, and anti-viral activity on Hepatitis C, DENV and yellow fever viruses. SFV785 inhibited DENV propagation without inhibiting DENV RNA synthesis or translation. The compound did not cause any changes in the cellular distribution of non-structural 3, a protein critical for DENV RNA synthesis, but altered the distribution of the structural envelope protein from a reticulate network to enlarged discrete vesicles, which altered the co-localization with the DENV replication complex. Ultrastructural electron microscopy analyses of DENV-infected SFV785-treated cells showed the presence of viral particles that were distinctly different from viable enveloped virions within enlarged ER cisternae. These viral particles were devoid of the dense nucleocapsid. The secretion of the viral particles was not inhibited by SFV785, however a reduction in the amount of secreted infectious virions, DENV RNA and capsid were observed. Collectively, these observations suggest that SFV785 inhibited the recruitment and assembly of the nucleocapsid in specific ER compartments during the DENV assembly process and hence the production of infectious DENV. SFV785 and derivative compounds could be useful biochemical probes to explore the DENV lifecycle and could also represent a new class of anti-virals.


TED-Face: Texture-Enhanced Deep Face Reconstruction in the Wild.
We present TED-Face, a new method for recovering high-fidelity 3D facial geometry and appearance with enhanced textures from single-view images. While vision-based face reconstruction has received intensive research in the past decades due to its broad applications, it remains a challenging problem because human eyes are particularly sensitive to numerically minute yet perceptually significant details. Previous methods that seek to minimize reconstruction errors within a low-dimensional face space can suffer from this issue and generate close yet low-fidelity approximations. The loss of high-frequency texture details is a key factor in their process, which we propose to address by learning to recover both dense radiance residuals and sparse facial texture features from a single image, in addition to the variables solved by previous work-shape, appearance, illumination, and camera. We integrate the estimation of all these factors in a single unified deep neural network and train it on several popular face reconstruction datasets. We also introduce two new metrics, visual fidelity (VIF) and structural similarity (SSIM), to compensate for the fact that reconstruction error is not a consistent perceptual metric of quality. On the popular FaceWarehouse facial reconstruction benchmark, our proposed system achieves a VIF score of 0.4802 and an SSIM score of 0.9622, improving over the state-of-the-art Deep3D method by 6.69% and 0.86%, respectively. On the widely used LS3D-300W dataset, we obtain a VIF score of 0.3922 and an SSIM score of 0.9079 for indoor images, and the scores for outdoor images are 0.4100 and 0.9160, respectively, which also represent an improvement over those of Deep3D. These results show that our method is able to recover visually more realistic facial appearance details compared with previous methods.


The biologic width around titanium implants: histometric analysis of the implantogingival junction around immediately and early loaded implants.
This study compared the dimensions of the peri-implant soft tissues around immediately and early loaded one-piece implants as well as conventionally loaded one-piece implants. Comparisons of the peri-implant soft tissue dimensions were made among four different loading periods. Forty-eight titanium sandblasted/acid-etched implants were placed in four foxhounds. The implants were placed at four time periods in groups of three. The first group (A) had implants placed 3 months before the placement of restorations. Further groups of three implants each were placed at 21 days (group B), 10 days (group C), and 2 days (group D) before restoration. Three months after abutment connection, all dogs were sacrificed. Histometric analysis of the undecalcified histologic sections included dimensional measurements of the sulcus depth plus junctional epithelium, the connective tissue contact area, and recession measured from the interface to the gingival margin. No statistically significant differences were observed among the four groups. The data suggest that the dimensions of the peri-implant soft tissues around immediately and early loaded one-piece implants are similar to those around conventionally loaded one-piece implants and comparable to the dimensions of the biologic width around natural teeth.


Diminished auditory sensory gating during active auditory verbal hallucinations.
Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH.


Evaluation of the i-STAT (portable clinical analyser) for measuring haematological parameters in Atlantic cod (Gadus morhua) at different CO2 and temperature conditions.
Portable clinical analysers are gradually being involved in on-site assessment of haematic parameters in fish. The purpose of this study was to evaluate the i-STAT portable clinical analyser (i-STAT PCA) for accuracy and reliability of measuring blood pH, partial pressure of oxygen (pO2), haematocrit, haemoglobin, sodium, potassium and calcium in Atlantic cod (Gadus morhua). Haematological parameters detected with the i-STAT PCA were compared with conventional laboratory techniques (CLTs). Two types of disposable cartridges were used (CHEM8+ and CG4+) with the i-STAT PCA, and experiments were performed at two different temperature regimes (5 °C and 15 °C) and four different carbon dioxide (CO2) levels (0%, 0.1%, 0.5% and 1%). All blood parameters measured with the i-STAT PCA showed heterogeneous inaccuracy under the tested conditions, but the highest discrepancies were registered in blood pO2. The i-STAT PCA systematically overestimated the pO2 measurements. Our research suggests that i-STAT PCA is not an appropriate tool for pO2 measurements especially in coldwater fish species. The i-STAT PCA consistently underestimated the pH and haematocrit values especially at a lower temperature, although those parameters indicate significant high correlation at 15 °C. Furthermore, the analysed ions showed overestimation of sodium and underestimation of potassium and calcium.


[Dietary factors and oral cancer: a case-control study in Greater Metropolitan São Paulo, Brazil].
Dietary factors associated with oral cancer were investigated in a case-control hospital-based study in the city of São Paulo, Brazil, from 1998 to 2002. A total of 835 subjects, 366 with histologically confirmed incident cases of oral-cavity or pharyngeal cancer and 469 controls participated in the study. Dietary data were collected with a food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (95%CI) were obtained from unconditional logistic regression, adjusted for potential confounders. Inverse associations with risk of oral cancer were found for the highest intake of beans, OR = 0.37 (95%CI: 0.22-0.64), raw vegetables, OR = 0.51 (95%CI: 0.29-0.93) and the intermediate tertile of rice and pasta intake, OR = 0.56 (95%CI: 0.38-0.83). Positive associations were observed for the highest intake of eggs, OR = 1.84 (95%CI: 1.23-2.75), potatoes, OR = 2.22 (95%CI: 1.53-3.25), and milk, OR= 1.80 (95%CI: 1.09-2.98). Some traditional Brazilian foods like rice and beans emerged as protective factors against oral cancer, independently of other risk factors.


The Association of Insomnia and Stress on Cardiovascular Risk Factors during COVID-19 Confinement in the Mexican Population.
During the pandemic confinement, the WHO changed the term "social distancing" to "physical distancing", to help people deal with the lack of social contact. As a result, there was an increase in mental health problems, including insomnia and stress, with a negative impact on cardiovascular health. The objective of this research was to identify the association between insomnia and stress and cardiovascular risk (CVR) during the pandemic in a sample of the general population in Mexico; the participants were chosen using the non-probabilistic method. The data were obtained from an online questionnaire about medical histories focused on cardiovascular risk, according to the Official Mexican Standards and Regulations for patients' clinical records, NOM-004-SSA3-2012, along with an index for the severity of insomnia, measured with a seven-item guide, and an instrument to measure stress. The data were analyzed with descriptive statistics for several different variables: sociodemographics, stress, insomnia, and cardiovascular risk. Cardiovascular risk was compared to insomnia and stress variables, which led to statistically significant differences and correlations between the variables. Participants were divided into four groups with respect to CVR, from low to very high CVR. This research demonstrated that women were more susceptible to stress and cardiovascular risk. However, stress was a more major indicator of CVR than insomnia, but in the high and very high CVR groups, insomnia contributed along with stress; coping strategies reduced the risk in the high CVR group but did not function as expected with respect to reducing risk in the very high CVR group. These findings suggest that sleep patterns and mental health alterations present during the pandemic may persist even when the pandemic was declared as having ended and may contribute to increases in cardiovascular risk in the long-term.


The role of retinol dehydrogenase 10 in the cone visual cycle.
Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown.


Utilization of distillers grains from the fermentation of sorghum or corn in diets for finishing beef and lactating dairy cattle.
Beef finishing and dairy lactation experiments were conducted to evaluate the nutritional value of distillers grains (DG) from sorghum or corn fermentation, in both wet (35.4% DM) and dry (92.2% DM) form (dairy trial only). In the finishing experiment, 60 yearling steers were used in a completely randomized design with three diets that were fed for 127 d: 1) control diet with 86% (DM basis) dry-rolled corn and no DG; 2) 30% of ration DM as wet corn DG in place of dry-rolled corn; and 3) 30% of ration DM as wet sorghum DG in place of dry-rolled corn. All diets contained a minimum of 6.8% degradable intake protein and 13.0% CP. Steers fed DG had 10% greater ADG (< 0.01) and 8% greater efficiency of gain (P < 0.01) than steers fed the control diet. Wet corn and sorghum DG resulted in similar ADG and efficiency of gain. Hot carcass weights, fat thickness, and yield grades were greater for steers fed DG than for controls (P < 0.07). Improvements in ADG and feed efficiency observed when DG replaced dry-rolled corn indicated that the NEg content of wet DG is approximately 29% greater than that of dry-rolled corn. In the dairy lactation experiment, 16 lactating Holstein cows (eight multiparous, including four fistulated) were used in a replicated 4 x 4 Latin square design with 4-wk periods. Corn and sorghum DG were fed at 15% of the ration DM in either wet or dry form. Diets were fed as total mixed rations that contained 50% of a 1:1 mixture of alfalfa and corn silages, 24.3% ground corn, and 9.1% soybean meal (DM basis). There was no effect of source or form of DG on DMI, ruminal pH and VFA, or in situ digestion kinetics of NDF from DG. Efficiency of milk production was unaffected by diet. Corn and sorghum DG resulted in relatively similar performance when fed to beef or dairy cattle in this study.


An analysis of free Web-based PHRs functionalities and I18n.
The growth of the Internet, Web technologies, and other electronic tools are allowing the public to become more informed and actively engaged in their health care than was possible in the past. Personal Health Records (PHR) offer users possibility of managing their own health data. Many patients are using PHRs to communicate with doctors in order to improve healthcare quality and efficiency. A large number of companies have emerged to provide consumers with the opportunity to use online PHRs within a healthcare platform, proposing different functionalities and services. This paper analyzes and assesses the functionalities and internationalization (i18n) of free Web based PHRs.


An examination of the association between premature mortality and life expectancy among men in Europe.
A feature of the health of men across Europe is their higher rates of premature mortality and shorter life expectancy at birth than women. Following the publication of the first State of Men's Health in Europe report, we sought to explore possible reasons. We analyzed trends in life expectancy at birth in 19 European Union member states (EU19) between 1999 and 2008 using mortality data obtained from Eurostat. We then used Pollard's decomposition method to identify the contribution of deaths from different causes and at different age groups to differences in life expectancy. Between 1999 and 2008, life expectancy at birth in the EU19 increased by 2.74 years for men and by 2.09 years for women. Most of these improvements were due to reductions in mortality at ages >60, with cardiovascular disease accounting for approximately half these improvements for men. In 2008, life expectancy of men in the EU19 was 5.92 years lower than that of women. Deaths from all major groups of causes, and at all ages, contributed to this gap, with external causes contributing 0.96 years, cardiovascular disease 1.80 years and neoplasms 1.61 years. Improvements in the life expectancy at birth of men and women have mostly occurred at older ages. There has been little improvement in the high rate of premature death in younger men, suggesting a need for interventions to tackle their high death rate.


Peer effects in early childhood education: testing the assumptions of special-education inclusion.
There has been a push in recent years for students with disabilities to be educated alongside their typically developing peers, a practice called inclusion. In this study, we sought to determine whether peer effects operate within early-childhood special-education (ECSE) classrooms in which preschoolers with disabilities are educated alongside typical peers. Peer effects specific to language growth were assessed for 670 preschoolers (mean age = 52 months) in 83 ECSE classrooms; 55% of the children had disabilities. We found that the average language skills of classmates, as assessed in the fall of the year, significantly predicted children's language skills in the spring (after controlling for their relative skill level in the fall); in addition, there was a significant interactive effect of disability status (i.e., the presence or absence of a disability) and peers' language skills. Peer effects were the least consequential for children without disabilities whose classmates had relatively strong language skills, and the most consequential for children with disabilities whose classmates had relatively poor language skills.


Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center.
Hematopoietic stem cell transplantation (HCT) in patients with prior or active invasive aspergillosis (IA) is a frequent consideration. We reviewed outcomes of 2319 patients who underwent transplantation between 1992 and 2001 in our institution, among whom 45 patients (1.9%) had a known history of IA before HCT. Posttransplantation IA occurred in 13 of these 45 patients with a pretransplantation history (29%). Nine infections were considered recurrent by anatomic site and timing. Compared with all other patients who received allogeneic HCT during the same period, patients with histories of IA had lower overall survival (56% versus 77%; P =.0001) and higher transplant-related mortality (TRM; 38% versus 21%; P =.0001) 100 days after HCT, associated mainly with IA and other pulmonary complications. Among patients with prior IA, posttransplantation IA occurred more frequently in patients who received <1 month of antifungal therapy before HCT (4/6 versus 6/39; P =.001). The probability of posttransplantation IA and overall survival among patients who received >1 month of antifungal therapy and had resolution of radiographic abnormalities were not different from those of patients without prior IA. Patients with prior IA who received conditioning with total body irradiation (TBI) had higher TRM compared with those who received nonmyeloablative and non-total body irradiation-based regimens (16/31 versus 2/14; P =.024). Thus, the duration of antifungal therapy before transplantation, the resolution of radiographic abnormalities, and conditioning regimens are important variables to consider for minimizing the risk for IA recurrence and TRM after allogeneic HCT.


Disrupted biographies and balancing identities: A qualitative study of cancer patients' communication with healthcare professionals about dependent children.
About 14% of cancer patients live with dependent children. Healthcare professionals are well placed to help patients support their children as part of a patient-centred practice. Children tend to appreciate open communication during the course of illness, but patients often find this difficult. However, research is unclear about patients' preferences and their willingness to talk with healthcare professionals about their dependent children. We conducted 15 in-depth interviews with patients from haematological (N = 11) and gynaecological oncology (N = 4). The interviews and subsequent analysis focused on patients' communicative preferences, taking the theoretical framework of "biographical disruption" as a starting point and using Jenkins' concept of identity as a social, relational and dynamic process. We identified two overall identities at stake for seriously ill patients with parental responsibility: "patient identity" and "parent identity." As "patients," patients were ambivalent about relating to their children, but as "parents" they wanted healthcare professionals to talk about their children. In order to be patient-centred, clinicians should, we suggest, acknowledge that patients have these conflicting perspectives and identities, which surface at various times and situations throughout their illness trajectories. Research is needed to further explore these findings in different illness groups and cultures.


Endocrine and metabolic changes in transition dairy cows are affected by prepartum infusions of a serotonin precursor.
Serotonin (5-HT) has been shown to be involved in calcium homeostasis, modulating calcium concentration in blood. In addition, 5-HT participates in a variety of metabolic pathways, mainly through the modulation of glucose and lipid metabolism. The hypothesis of the present study was that the prepartum administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, would affect endocrine systems related to calcium homeostasis, and interact with other endocrine and metabolic pathways during the transition period. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (control group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before estimated parturition date and ended the day of parturition, resulting in a minimum of 4 d of infusion (8.4 ± 0.7 d of infusion). Until parturition, blood samples were collected before the daily infusions, and postpartum daily until d 7, and on d 30. Plasma concentrations of parathyroid hormone (PTH) were transiently increased at parturition and on d 1 in control cows. In the 5-HTP group PTH remained unchanged. The concentration of pyridinoline (PYD), an established marker for calcium release from the bone to the bloodstream, increased on d 1 postpartum only in the 5-HTP group. In control cows, PYD concentrations did not change on d 1 postpartum. Melatonin concentrations were slightly but significantly increased in the 5-HTP group compared with the control group. Insulin concentrations decreased in both groups postpartum. Before parturition, leptin concentrations decreased in both groups and remained at this level until d 30 postpartum. Plasma IgG concentrations decreased in both groups on d -1 postpartum. Haptoglobin increased in both groups on d -1 and remained at this level until d 7 postpartum. No differences between groups were observed for insulin, glucagon, IgG, leptin, adiponectin, and haptoglobin concentrations. The results obtained in the present study evidenced that 5-HT is regulating calcium homeostasis independent of PTH. The lack of treatment effects on IgG and on other hormones and metabolites indicates that 5-HTP did not affect these other metabolic pathways and the IgG concentration during the transition period.


Tacrolimus 0.1% ointment in nail psoriasis: a randomized controlled open-label study.
Despite recent advances in the treatment of psoriasis, the therapeutic options for nail psoriasis are very limited, particularly when this is the only manifestation of the disease. We performed a randomized controlled open-label study to assess the efficacy and safety of a topical treatment with tacrolimus 0.1% ointment in nail psoriasis. In each patient, tacrolimus 0.1% ointment was prescribed for application only on the affected nails of a randomly selected hand for 12 weeks, whereas nails of the other hand did not receive any treatment. Severity of nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI) score. We enrolled 21 consecutive psoriatic patients. At week 12, a statistically significant (P < 0.001) improvement was obtained in the treated hands with respect to the hands used as control (NAPSI score absolute change 13.0 and 3.0 respectively). Each of the enrolled patients concluded the period of treatment, but one patient was withdrawn from tacrolimus application after 9 weeks because of the appearance of acute paronychia. Our study showed that tacrolimus 0.1% ointment may be an efficacious and safe therapeutic opportunity in the treatment of nail psoriasis. Our data should be confirmed by a double-blind study with a larger sample of patients.


Optimization of DNA hybridization efficiency by pH-driven nanomechanical bending.
The accessibility and binding affinity of DNA are two key parameters affecting the hybridization efficiency in surface-based biosensor technologies. Better accessibility will result in a higher hybridization efficiency. Often, mixed ssDNA and mercaptohexanol monolayers are used to increase the hybridization efficiency and accessibility of surface-bound oligonucleotides to complementary target DNA. Here, no mercaptohexanol monolayer was used. We demonstrate by differential microcantilever deflection measurements at different pH that the hybridization efficiency peaks between pH 7.5 and 8.5. At low pH 4.5, hydration and electrostatic forces led to tensile surface stress, implying the reduced accessibility of the bound ssDNA probe for hybridization. In contrast, at high pH 8.5, the steric interaction between neighboring ssDNA strands was decreased by higher electrostatic repulsive forces, bending the microcantilever away from the gold surface to provide more space for the target DNA. Cantilever deflection scales with pH-dependent surface hybridization efficiency because of high target DNA accessibility. Hence, by changing the pH, the hybridization efficiency is adjusted.


New potent antioxidative o-dihydroxyisoflavones in fermented Japanese soybean products.
A potent antioxidative 6-hydroxydaidzein (6-OHD) was newly isolated from soybean koji fermented with Aspergillus oryzae. 6-OHD, in addition to 8-hydroxydaidzein and 8-hydroxygenistein, were found to be present in various fermented soybean products, including their koji. Considering that these o-dihydroxyisoflavones had strong antioxidative activities, they may contribute to protecting from oxidative deterioration during the processing of fermented soybean products.


Biogenesis of 2-phenylethanol in rose flowers: incorporation of [2H8]L-phenylalanine into 2-phenylethanol and its beta-D-glucopyranoside during the flower opening of Rosa 'Hoh-Jun' and Rosa damascena Mill.
To clarify the biosynthetic pathway to 2-phenylethanol (2), the deuterium-labeled putative precursor, [2H8]L-phenylalanine ([2H8-1]), was fed to the flowers of Rosa 'Hoh-Jun' and R. damascena Mill. throughout maturation, ceasing feeding at the commencement of petal unfurling and at full bloom. Based on GC-MS analyses, [2H8]-1 was incorporated into both 2 and 2-phenylethyl beta-D-glucopyranoside (3) when the flowers were fed until full bloom, whereas no such incorporation into 2 was apparent when feeding was ceased earlier. In both species of rose, the labeling pattern for 2 was almost identical to that for 3, and indicated the presence of [2H6]-, [2H7]- and [2H8]-2, and [2H6]-, [2H7]- and [2H8]-3. This may be ascribed to the equilibrium between 2 and 3. The labeling pattern for 2 and 3 also indicated that these compounds were produced from 1 via several routes, the route involving phenylpyruvic acid being the major one.


[Use of movalis in treatment of dorsopathy].
In regard to therapeutic effect of different medications used in dorsopathy treatment, non-steroid anti-inflammatory drugs rank first. Compounds selectively blocking COX-2 received special attention due to their minimal impact on COX-1 that provides good anti-inflammatory and analgesic effect with simultaneous dramatic reduction of ulcerogenic activity. One of the first drugs with such an action is Movalis (meloxicam). Thirty patients were divided into 2 groups, the first including 22 patients with vertebral diseases and musculotonic syndromes; patients of the second group (8) had a pain syndrome caused by disk herniation. During the first 3 days Movalis was administered in the form of injections (15 mg/day) and in the same doses in tablets for the following 20 days. After the treatment course, complete arrest of pain syndrome was observed in 33.3% patients, significant improvement--in 53.3% and insignificant effect--in 13.3%. Patients with reflex pain and musculotonic syndromes had a good analgesic effect after 3-day course of intramuscular injections, with the effect being mostly expressed in 8-10 days. Patients with diskogenic compressive radicular syndrome demonstrated a stable analgesic effect after a week of Movalis intake in tablet form. Movalis is well tolerated; side effects have occurred in 10 patients but they were minimal and did not lead to the change of medication dose or additional therapy.


A Multi-Method Approach for Quantification of Surface Coatings on Commercial Zinc Oxide Nanomaterials.
Surface functionalization is a key factor for determining the performance of nanomaterials in a range of applications and their fate when released to the environment. Nevertheless, it is still relatively rare that surface groups or coatings are quantified using methods that have been carefully optimized and validated with a multi-method approach. We have quantified the surface groups on a set of commercial ZnO nanoparticles modified with three different reagents ((3-aminopropyl)-triethoxysilane, caprylsilane and stearic acid). This study used thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FT-IR) of evolved gases and quantitative solution 1H nuclear magnetic resonance (NMR) for quantification purposes with 13C-solid state NMR and X-ray photoelectron spectroscopy to confirm assignments. Unmodified materials from the same suppliers were examined to assess possible impurities and corrections. The results demonstrate that there are significant mass losses from the unmodified samples which are attributed to surface carbonates or residual materials from the synthetic procedure used. The surface modified materials show a characteristic loss of functional group between 300-600 °C as confirmed by analysis of FT-IR spectra and comparison to NMR data obtained after quantitative release/extraction of the functional group from the surface. The agreement between NMR and TGA estimates for surface loading is reasonably good for cases where the functional group accounts for a relatively large fraction of the sample mass (e.g., large groups or high loading). In other cases TGA does not have sufficient sensitivity for quantitative analysis, particularly when contaminants contribute to the TGA mass loss. X-ray photoelectron spectroscopy and solid state NMR for selected samples provide support for the assignment of both the functional groups and some impurities. The level of surface group loading varies significantly with supplier and even for different batches or sizes of nanoparticles from the same supplier. These results highlight the importance of developing reliable methods to detect and quantify surface functional groups and the importance of a multi-method approach.


Rates and Trends of Endotracheal Intubation in Patients With Status Epilepticus.
Among patients with status epilepticus, we sought to determine the rate of endotracheal intubation, identify the physician specialties responsible for endotracheal intubation, and characterize the trend in use of endotracheal intubation over the last 20 years. We performed a cross-sectional study using data from 2 sources. First, we used inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. Patients with status epilepticus were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, and those who underwent endotracheal intubation were identified based on Current Procedural Terminology codes. Medical specialties of providers performing intubation were identified based on Healthcare Provider Taxonomy Codes. Second, we used claims data from the National Inpatient Sample (NIS) to estimate the annual rates and trends of endotracheal intubation and tracheostomy among patients with status epilepticus from 1995 to 2014. Among 1971 Medicare beneficiaries with status epilepticus, 566 (29%) patients underwent endotracheal intubation. 375 (66%) patients were intubated on admission. The most common medical providers performing intubation in patients with status epilepticus were emergency medicine physicians (50.4%), anesthesiologists (16.4%), and pulmonary medicine physicians (10.1%). Neurologists accounted for 1.7% of all intubations. Among individuals with status epilepticus identified in the NIS, 248 681 (41.7%) were intubated. The proportion of patients intubated increased from 29.5% (95% confidence interval [CI]: 27.8%-31.3%, P = .018) in 1995 to 50.8% (95% CI: 49.6%-52%, P = .012) in 2014. The proportion of patients with status epilepticus who underwent tracheostomy increased from 2.2% (95% CI: 1.7%-2.7%, P = .005) in 1995 to 3.4% (95% CI: 3%-3.9%, P = .004) in 2014. Approximately 1 in 3 patients with status epilepticus undergo endotracheal intubation. Over the last 20 years, the proportion of patients with status epilepticus undergoing endotracheal intubation has almost doubled. Neurologists perform a small percentage of these intubations.


Trophic response of rat brown fat by glucose feeding: involvement of sympathetic nervous system.
Brown adipose tissue has earlier been suggested as an important site of the diet-induced thermogenesis that results from cafeteria feeding in rats. The aim of the present communication has been to see if any defined component of this diet can mimic the effects of the diet on the trophic response of brown fat and if these effects are mediated by the sympathetic nervous system. Rats fed a lipid emulsion did not show hypertrophy of brown adipose tissue. Rats fed a glucose solution, whether voluntarily or by force feeding, showed a clear trophic response of brown fat, as seen by the morphology of the tissue and its increased wet weight, increased protein content, increased total and specific cytochrome c oxidase activity, and increased mitochondrial guanosine diphosphate binding. Chemical sympathectomy of young rats by guanethidine prior to glucose feeding impaired the glucose-induced effects on brown fat. beta-Adrenergic blockade in adult rats also tended to depress the glucose effect. Consequently we conclude that chronic glucose ingestion can mimic cafeteria feeding with respect to the trophic response of brown fat and that an intact sympathetic nervous system is required for the mediation of the glucose effect to the brown adipose tissue.


Regulation of cell proliferation in a stratified culture system of epithelial cells from prostate tissue.
Mechanisms controlling epithelial proliferation and differentiation in the prostate have been primarily investigated in mouse models. The regulation of proliferation and differentiation is poorly understood in human prostate epithelial cells. In vivo, the glandular prostate epithelium consists of a p63-positive proliferating basal cell layer and a post-mitotic p27-positive secretory cell layer. We have established an organized stratified culture system of human primary prostate epithelial cells to gain insight into mechanisms regulating proliferation and differentiation. In this system, expression of p63 is observed in the bottom layer. In addition, BrdU incorporation persists even though cells are confluent. In contrast, in the upper layer, p63 expression is greatly diminished, p27 is expressed, and the cells are growth arrested. Overexpression of cyclin D1 or knockdown of p27 does not increase proliferation. After inactivation of the nuclear phosphoprotein Rb, the cell layers remain organized and cell proliferation increases only in the bottom layer. Furthermore, the expression of p63 remains confined to the bottom layer after Rb inactivation. Altogether, this in vitro model recapitulates certain aspects of in vivo growth regulation and differentiation and suggests that the loss of Rb family proteins in human cells trigger hyperplasia but is not sufficient for transformation.


Nemo kinase phosphorylates β-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-β-catenin.
Frizzled planar cell polarity (PCP) signaling regulates cell motility in several tissues, including ommatidial rotation in Drosophila melanogaster. The Nemo kinase (Nlk in vertebrates) has also been linked to cell-motility regulation and ommatidial rotation but its mechanistic role(s) during rotation remain obscure. We show that nemo functions throughout the entire rotation movement, increasing the rotation rate. Genetic and molecular studies indicate that Nemo binds both the core PCP factor complex of Strabismus-Prickle, as well as the E-cadherin-β-catenin (E-cadherin-Armadillo in Drosophila) complex. These two complexes colocalize and, like Nemo, also promote rotation. Strabismus (also called Vang) binds and stabilizes Nemo asymmetrically within the ommatidial precluster; Nemo and β-catenin then act synergistically to promote rotation, which is mediated in vivo by Nemo's phosphorylation of β-catenin. Our data suggest that Nemo serves as a conserved molecular link between core PCP factors and E-cadherin-β-catenin complexes, promoting cell motility.