Psychotic Experiences and Neuropsychological Functioning in a Population-based Sample.
Psychotic experiences in early life are associated with neuropsychological impairment and the risk for later psychiatric disorders. Psychotic experiences are also prevalent in adults, but neuropsychological investigations spanning adulthood are limited, and confounding factors have not been examined rigorously. To characterize neuropsychological functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and familial factors and investigating the effect of age. The South East London Community Health (SELCoH) study is a population-based household survey of physical and mental health in individuals 16 years or older conducted from June 1, 2008, to December 31, 2010, in 2 London boroughs. The study included 1698 participants from 1075 households. Data were analyzed from May 6, 2014, to April 22, 2015. Psychotic experiences measured using the Psychosis Screening Questionnaire. Neuropsychological functioning measured using tests assessing verbal knowledge (Wechsler Test of Adult Reading), working memory (Spatial Delayed Response Task), memory (Visual Object Learning Task), and processing speed (digit symbol coding task). A composite IQ score of general cognitive ability was calculated. A total of 1677 participants with a mean (SD) age of 40 (17) years were included in the analysis. Compared with the group without psychotic experiences, the 171 (9.7%) adults with psychotic experiences did not show a statistically significant impairment on mean (SD) measures of IQ (95.25 [16.58] vs 100.45 [14.77]; Cohen d, -0.22; P = .06) or processing speed (40.63 [13.06] vs 42.17 [13.79]; Cohen d, -0.03; P = .73) but were impaired on measures of verbal knowledge (31.36 [15.78] vs 38.83 [12.64]; Cohen d, -0.37; P = .003), working memory (20.97 [4.12] vs 22.51 [3.26]; Cohen d, -0.34; P = .005), and memory (43.80 [8.45] vs 46.53 [7.06]; Cohen d, -0.28; P = .01). Only participants 50 years and older with psychotic experiences showed medium to large impairments in neuropsychological functioning (mean [SD]) on measures of IQ (81.22 [15.97] vs 91.28 [14.31]; Cohen d, -0.70), verbal knowledge (28.31 [13.83] vs 38.51 [11.50]; Cohen d, -0.88), working memory (19.11 [4.77] vs 21.99 [3.42]; Cohen d, -0.82), and memory (39.17 [8.23] vs 44.09 [6.51]; Cohen d, -0.45) after adjusting for socioeconomic status, cannabis use, and common mental disorders. Medium impairments (mean [SD]) on measures of working memory (21.27 [3.64] vs 22.62 [2.97]; Cohen d, -0.45) and memory (44.32 [5.84] vs 46.91 [5.74]; Cohen d, -0.45) were seen in those aged 35 to 49 years and on a measure of verbal knowledge (30.81 [14.17] vs 37.60 [10.48]; Cohen d, -0.62) in those aged 16 to 24 years. First-degree relatives of adults with psychotic experiences showed a small impairment on a measure of verbal knowledge (34.71 [12.10] vs 38.63 [10.97]; Cohen d, -0.36; P = .02), and unrelated cohabitants showed no neuropsychological impairment. The profile of cognitive impairment in adults with psychotic experiences differed from that seen in adults with psychotic disorders, suggesting important differences between subclinical and clinical psychosis.


Injectable Nano Whitlockite Incorporated Chitosan Hydrogel for Effective Hemostasis.
Uncontrolled bleeding can lead to many complications that might cause multiple organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca18Mg2(HPO4)2(PO4)12) that would release Ca2+, Mg2+, and PO43- ions that would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague-Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.


Transgenic Pm3 multilines of wheat show increased powdery mildew resistance in the field.
Resistance (R) genes protect plants very effectively from disease, but many of them are rapidly overcome when present in widely grown cultivars. To overcome this lack of durability, strategies that increase host resistance diversity have been proposed. Among them is the use of multilines composed of near-isogenic lines (NILs) containing different disease resistance genes. In contrast to classical R-gene introgression by recurrent backcrossing, a transgenic approach allows the development of lines with identical genetic background, differing only in a single R gene. We have used alleles of the resistance locus Pm3 in wheat, conferring race-specific resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici), to develop transgenic wheat lines overexpressing Pm3a, Pm3c, Pm3d, Pm3f or Pm3g. In field experiments, all tested transgenic lines were significantly more resistant than their respective nontransformed sister lines. The resistance level of the transgenic Pm3 lines was determined mainly by the frequency of virulence to the particular Pm3 allele in the powdery mildew population, Pm3 expression levels and most likely also allele-specific properties. We created six two-way multilines by mixing seeds of the parental line Bobwhite and transgenic Pm3a, Pm3b and Pm3d lines. The Pm3 multilines were more resistant than their components when tested in the field. This demonstrates that the difference in a single R gene is sufficient to cause host-diversity effects and that multilines of transgenic Pm3 wheat lines represent a promising strategy for an effective and sustainable use of Pm3 alleles.


[Regulation of cardiac calcium current by cGMP/NO route].
Early studies in whole heart indicated that cGMP antagonized the positive inotropic effects of catecholamines and cAMP. Since the L-type Ca2+ channel current (ICa) plays a predominant role in the initiation and development of cardiac electrical and contractile activities, regulation of ICa by cGMP pathways has received much attention over the last ten years. Patch-clamp measurements of ICa in isolated cardiac myocytes reveal at least three different cGMP effectors that may participate to different degrees in different animal species and cardiac tissues in the regulation of ICa by cGMP. In frog ventricular myocytes, cGMP inhibits ICa by stimulation of a cGMP-stimulated cAMP phosphodiesterase (PDE2), whereas in rat ventricular myocytes, cGMP predominantly inhibits ICa via a mechanism involving activation of a cGMP-dependent protein kinase (cGMP-PK). In guinea pig, frog and human cardiomyocytes, cGMP can also stimulate ICa via an inhibition of a cGMP-inhibited cAMP phosphodiesterase (PDE3). This effect is most predominant in human atrial myocytes and appears readily during an activation of the soluble guanylate cyclase activity by low concentrations of nitric oxide (NO)-donors. Biochemical characterization of the endogenous phosphodiesterases and cGMP-PK in purified cardiac myocytes provide further evidence in support of these mechanisms of cGMP action on ICa. However, the regulation of cGMP levels by a variety of agents is not always consistent with their effects on contractility. In particular, the participation of cGMP and NO pathways in the regulation of cardiac ICa and contractility by acetylcholine is still questionable.


The Ajellomycetaceae, a new family of vertebrate-associated Onygenales.
Phylogenies inferred from the analysis of DNA sequence data have shown that the Onygenales contains clades that do not correspond with previously described families. One lineage identified in recent molecular phylogenetic studies includes the dimorphic pathogens belonging to the genera Ajellomyces, Emmonsia and Paracoccidioides. To evaluate the degree of support for this lineage and determine whether it includes additional taxa, we examined relationships among the members of this clade and selected saprobic onygenalean taxa based on maximum-parsimony analyses of partial nuclear large RNA subunit (LSU) and internal transcribed spacer (ITS) sequences. A clade distinct from the Onygenaceae was found to encompass Ajellomyces (including the anamorph genera Blastomyces, Emmonsia and Histoplasma) and Paracoccidioides brasiliensis. The members of this lineage are saprobic and pathogenic vertebrate-associated taxa distinguished by their globose ascomata with coiled appendages, muricate globose or oblate ascospores, and lack of keratinolytic activity. Anamorphs are solitary aleurioconidia or irregular alternate arthroconidia. Based on molecular data and on morphological and physiological similarities among these taxa, we propose the new family, Ajellomycetaceae.


Antibiotic use in dairy herds in the Netherlands from 2005 to 2012.
The aim of this study was to examine the variation in antibiotic use and the effects of external factors on trends in antibiotic use at the herd level by using the number of daily dosages as an indicator for antibiotic use. For this purpose, antibiotic use was analyzed in 94 dairy herds in the Netherlands from 2005 to 2012. The herds were divided into 3 groups of farmers: one group was guided in their antibiotic use from 2008 to 2010 as part of the project, whereas the other 2 groups were not actively guided. The farms were located in 10 of the 12 provinces and were clients of 32 of the 300 veterinary practices that treat cattle. Sales invoices from the veterinary practices provided the antibiotic and cost data for the participating farmers. The number of animal-defined daily dosages (ADDD) indicates the number of days per year that the average cow in a herd is given antibiotic treatment. The average ADDD for all farms from 2005 to 2012 was 5.86 (standard deviation=2.14); 68% of ADDD were used for udder health, 24% for clinical mastitis and 44% for dry-cow therapy. Variation in ADDD among herds decreased during the study period. The trend in ADDD can be described as having 3 phases: (1) a period of increasing use coinciding with little public concern about antibiotic use (2005-2007), (2) a period of growing awareness and stabilization of use (2007-2010), and (3) a period of decreasing use coinciding with increasing societal concerns (2010-2012). The greatest reduction in use was for drugs other than those used to treat the udder. Drug use for mastitis treatment fell considerably in the final year of the study period, whereas farmers were reluctant to reduce use for dry-cow therapy. Almost 40% of the herds were given less than 2.5 ADDD for dry-cow therapy, which is equivalent to 2.5 tubes per average cow in the herd, and 20% used more than 3 tubes per cow. Use of third- and fourth-generation cephalosporins and fluoroquinolones dropped from 18% of ADDD during 2005 to 2010 to 1% in 2012, with a shift toward penicillins and broad spectrum drugs. The ADDD was 22% lower in 2012 than 2007, the year of the highest usage. The decrease in ADDD over time varied between the 3 groups of farmers. During the second phase of the study, the guided group began to display a reduction in use, whereas the other groups only displayed a significant reduction in the third phase. The reduction in antibiotic use has resulted in lower veterinary costs per cow in recent years.


'What about the coffee break?': Designing virtual conference spaces for conviviality.
Geography, like many other disciplines, is reckoning with the carbon intensity of its practices and rethinking how activities such as annual meetings are held. The Climate Action Task Force of the American Association of Geographers (AAG), for example, was set up in 2019 and seeks to transform the annual conference in light of environmental justice concerns. Mirroring shifts it geographic practice across the globe, these efforts point to a need to understand how new opportunities for knowledge production such as online events can operate effectively. In this article, we offer suggestions for best practice in virtual spaces arising from our Material Life of Time conference held in March 2021, a two day global event that ran synchronously across 15 time zones. Given concerns about lack of opportunities for informal exchanges at virtual conferences, or the "coffee break problem", we designed the event to focus particularly on opportunities for conviviality. This was accomplished through a focus on three key design issues: the spatial, the temporal and the social. We review previous work on the benefits and drawbacks of synchronous and asynchronous online conference methods and the kinds of geographic communities they might support. We then describe our design approach and reflect on its effectiveness via a variety of feedback materials. We show that our design enabled high delegate satisfaction, a sense of conviviality, and strong connections with new colleagues. However we also discuss the problems with attendance levels and external commitments which hampered shared time together. We thus call for collective efforts to support the 'event time' of online meetings, rather than expectations to fit them around everyday tasks. Even so, our results suggest that synchronous online events need not result in geographical exclusions linked to time zone differences, and we outline further recommendations for reworking the spacetimes of the conference.


Treatment of epilepsy in the elderly.
The elderly are the most rapidly growing segment of the population, and the incidence of epilepsy in persons over 65 is higher than in any other age group. In nursing homes, its incidence is even higher than in community-dwelling persons of similar ages. About 10% of nursing home residents are being treated with antiepileptic drugs (AEDs), with an "epilepsy/seizure" indication reported for about 7.7% of this use. Almost all elderly patients are being treated with AEDs introduced before 1978--phenytoin, carbamazepine, valproate, and barbiturates. However, age-related changes in protein binding, decreases in hepatic and renal clearance, alterations in gastrointestinal absorption, and interactions with drugs used for other conditions make the choice of the best AED difficult. AEDs that do not interact with other drugs, are not metabolized by the liver, and are readily absorbed may offer benefits for the elderly. To complicate matters, the elderly are not a homogeneous population. Today there are many AEDs to choose from, and some of the newer AEDs have more favorable characteristics than the older ones. Choice of an AED should be made on an individual basis, considering the cost of the drug, the cost of consequences of drug-drug interactions, and expenses associated with acute and chronic adverse effects. In other words, clinical skills rather than formulaic approaches are needed to match detailed knowledge of each patient's characteristics with the properties of the various AEDs.


Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures.
While the use of electronic methods to collect patient-reported outcome (PRO) data in clinical trials continues to increase, it remains the case that many PRO measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic (ePROM) format is required to preserve the integrity of the measure and ensure a "faithful migration". Relevant literature has long called out the importance of following migration best practices during this process; however, such best practices are distributed across multiple documents. This article consolidates and builds upon existing ePROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence-base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.


SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE.
Hereditary angioedema with C1 Inhibitor deficiency (C1-INH-HAE) is caused by a constellation of variants of the SERPING1 gene (n = 809; 1,494 pedigrees), accounting for 86.8% of HAE families, showing a pronounced mutagenic liability of SERPING1 and pertaining to 5.6% de novo variants. C1-INH is the major control serpin of the kallikrein-kinin system (KKS). In addition, C1-INH controls complement C1 and plasminogen activation, both systems contributing to inflammation. Recognizing the failed control of C1s protease or KKS provides the diagnosis of C1-INH-HAE. SERPING1 variants usually behave in an autosomal-dominant character with an incomplete penetrance and a low prevalence. A great majority of variants (809/893; 90.5%) that were introduced into online database have been considered as pathogenic/likely pathogenic. Haploinsufficiency is a common feature in C1-INH-HAE where a dominant-negative variant product impacts the wild-type allele and renders it inactive. Small (36.2%) and large (8.3%) deletions/duplications are common, with exon 4 as the most affected one. Point substitutions with missense variants (32.2%) are of interest for the serpin structure-function relationship. Canonical splice sites can be affected by variants within introns and exons also (14.3%). For noncanonical sequences, exon skipping has been confirmed by splicing analyses of patients' blood-derived RNAs (n = 25). Exonic variants (n = 6) can affect exon splicing. Rare deep-intron variants (n = 6), putatively acting as pseudo-exon activating mutations, have been characterized as pathogenic. Some variants have been characterized as benign/likely benign/of uncertain significance (n = 74). This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. Rare benign variants could contribute as disease modifiers. Gonadal mosaicism in C1-INH-HAE is rare and must be distinguished from a de novo variant. Situations with paternal or maternal disomy have been recorded (n = 3). Genotypes must be interpreted with biological investigation fitting with C1-INH expression and typing. Any SERPING1 variant reminiscent of the dysfunctional phenotype of serpin with multimerization or latency should be identified as serpinopathy.


Efficacy of cefoxitin versus carbapenem in febrile male urinary tract infections caused by extended spectrum beta-lactamase-producing Escherichia coli: a multicenter retrospective cohort study with propensity score analysis.
Cefoxitin has demonstrated good in vitro activity against extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) and is regarded as a carbapenem-sparing beta-lactam alternative in urinary tract infections. Its efficacy has never been compared to carbapenems in male UTIs. Our study aimed to compare the clinical and microbiological efficacy of cefoxitin (FOX) and carbapenems (CP) in febrile M-UTI due to ESBL-Ec (F-M-UTI). We conducted a multicenter retrospective cohort study of patients with F-M-UTI treated with FOX or CP as definitive therapy, between January 2013 and June 2015, in six French acute care teaching hospitals. The clinical and microbiological efficacies of FOX and CP were compared using multivariable logistic regression models, adjusting for propensity scores. Of the 66 patients included, 23 patients in FOX group and 27 in CP group had clinical assessment at follow-up. Median follow-up after end of treatment was 63 days (interquartile range 26-114). Clinical success was observed for 17/23 (73.9%) and 22/27 (81.5%) patients and microbiological success for 11/19 (57.9%) and for 6/12 (50.0%) patients in FOX and CP groups respectively. We did not find any significant difference for clinical (OR = 0.90, 95% CI [0.12; 6.70]) neither microbiological (OR = 0.85, 95% CI [0.05; 14.00]) success between CP and FOX groups in univariate and multivariable models. In the FOX group, high dose with use of continuous infusion was associated with clinical success. These results add evidence that FOX is an effective alternative treatment to carbapenems for M-UTI caused by ESBL-Ec, particularly when high doses and continuous infusion are used.


Unveiling the Effect of Magnetic Noise in the Coherence of Single-Molecule Quantum Processors.
Quantum bits (qubits) constitute the most elementary building-blocks of any quantum technology, where information is stored and processed in the form of quantum superpositions between discrete energy levels. In particular, the fabrication of quantum processors is a key long-term goal that will allow us conducting specific tasks much more efficiently than the most powerful classical computers can do. Motivated by recent experiments in which three addressable spin qubits are defined on a potential single-molecule quantum processor, namely the [Gd(H2O)P5W30O110]12- polyoxometalate, we investigate the decohering effect of magnetic noise on the encoded quantum information. Our state-of-the-art model, which provides more accurate results than previous estimates, show a noticeable contribution of magnetic noise in limiting the survival timescale of the qubits. Yet, our results suggest that it might not be the only dephasing mechanism at play but other mechanisms, such as lattice vibrations and physical movement of magnetic nuclei, must be considered to understand the whole decoherence process.


Fluorescence of the single tryptophan of cutinase: temperature and pH effect on protein conformation and dynamics.
The cutinase from Fusarium solani pisi is an enzyme with a single L-tryptophan (Trp) involved in a hydrogen bond with an alanine (Ala) residue and located close to a cystine formed by a disulfide bridge between two cysteine (Cys) residues. The Cys strongly quenches the fluorescence of Trp by both static and dynamic quenching mechanisms. The Trp fluorescence intensity increases by about fourfold on protein melting because of the disruption of the Ala-Trp hydrogen bond that releases the Trp from the vicinity of the cystine residue. The Trp forms charge-transfer complexes with the disulfide bridge, which is disrupted by UV light irradiation of the protein. This results in a 10-fold increase of the Trp fluorescence quantum yield because of the suppression of the static quenching by the cystine residue. The Trp fluorescence anisotropy decays are similar to those in other proteins and were interpreted in terms of the wobbling-in-cone model. The long relaxation time is attributed to the Brownian rotational correlation time of the protein as a whole below the protein-melting temperature and to protein-backbone dynamics above it. The short relaxation time is related to the local motion of the Trp, whose mobility increases on protein denaturation.


Molecular Consequences of the Myopathy-Related D286G Mutation on Actin Function.
Myopathies are notably associated with mutations in genes encoding proteins known to be essential for the force production of skeletal muscle fibers, such as skeletal alpha-actin. The exact molecular mechanisms by which these specific defects induce myopathic phenotypes remain unclear. Hence, in the present study, to better understand actin dysfunction, we conducted a molecular dynamic simulation together with ex vivo experiments of the specific muscle disease-causing actin mutation, D286G located in the actin-actin interface. Our computational study showed that D286G impairs the flexural rigidity of actin filaments. However, upon activation, D286G did not have any direct consequences on actin filament extension. Hence, D286G may alter the structure of actin filaments but, when expressed together with normal actin molecules, it may only have minor effects on the ex vivo mechanics of actin filaments upon skeletal muscle fiber contraction.


Response and Tolerance of Female and/or Elderly PMHS to Lateral Impact.
Eight whole fresh-frozen cadavers (6 female, 2 male) that were elderly and/or female were laterally impacted using UMTRI's dual-sled side-impact test facility. Cadavers were not excluded on the basis of old age or bone diseases that affect tolerance. A thinly padded, multi-segment impactor was used that independently measured force histories applied to the shoulder, thorax, abdomen, greater trochanter, iliac wing, and femur of each PMHS. Impactor plates were adjusted vertically and laterally toward the subject so that contact with body regions occurred simultaneously and so that each segment contacted the same region on every subject. This configuration minimized the effects of body shape on load sharing between regions. Prior to all tests, cadavers were CT scanned to check for pre-existing skeletal injuries. Cadavers were excluded if they had preexisting rib fractures or had undergone CPR. Cadavers were instrumented with strain gages at the posterolateral, lateral, and anterolateral portions of the struck-side ribs, and chestbands were positioned on the upper and lower thorax. Cadavers were first impacted at 3 m/s. If two or fewer rib fractures occurred, as determined using strain gage data and a post-test CT scan, a second impact was performed at 6 m/s on the contralateral side of the body. Five of the eight 3-m/s tests produced AIS 3+ level injuries. All three of the 6-m/s tests produced AIS 3+ injury. Response corridors were developed for each body region using the Maltese alignment method with impulse-momentum normalization. Corridors describing upper and lower thorax deflection were generated from chestband data. An injury risk curve developed from the deflections associated with AIS 3+ injury associates a 50% probability of AIS 3+ rib fracture with 25.6% half-thorax deflection for the population used in this study.


Data Processing for Scientists.
This brief survey of integrated and electronic data processing has touched on such matters as the origin of the concepts, their use in business, machines that are available, indexing problems, and, finally, some scientific uses that surely foreshadow further development. The purpose of this has been to present for the consideration of scientists a point of view and some techniques which have had a phenomenal growth in the business world and to suggest that these are worth consideration in scientific data-handling problems (30). To close, let me quote from William Bamert on the experience of the C. and O. Railroad once more (8, p. 121): "Frankly, we have been asked whether we weren't planning for Utopia-the implication being that everyone except starry-eyed visionaries knows that Utopia is unattainable. Our answer is that of course we are! Has anyone yet discovered a better way to begin program planning of this nature? Our feeling is that compromise comes early enough in the normal order of things."


Outcomes of stents covering the deep femoral artery origin.
To investigate the impact of coverage of the deep femoral artery (DFA) by stents during endovascular treatment of proximal superficial femoral artery (SFA) lesions involving its ostium on the patency of both femoral arteries. We retrospectively analysed 171 limbs of 143 patients who had been treated with femoral bifurcation stenting. According to the stenting strategies, 101 limbs with DFA coverage (group 1) and 70 limbs without DFA coverage (group 2) were compared. SFA and DFA patency was assessed by intra-arterial or computed tomography angiography or duplex ultrasound. Baseline characteristics were similar between groups, except for stent diameter. Flow limitations in DFAs were observed in 13 limbs divided similarly between the groups (8.9% vs. 5.7%, p=0.320). During a median follow-up of 18 months, there was a trend towards higher SFA patency at one and three years in group 1 (83% and 63% vs. 75% and 50%, p=0.124). DFA patency at one and three years was not different between groups (88% and 77% vs. 83% and 71%, p=0.488). Jailing of the DFA origin by SFA ostial stenting did not result in a significant increase in the acute or later loss of patency in either femoral artery.


Suicide later in life: challenges and priorities for prevention.
Suicide in later life is a major public health concern in the U.S., where more than 6,000 older adults take their own lives every year. Suicide prevention in this age group is made challenging by the high lethality of older adults' suicidal behavior; few survive their first attempt to harm themselves. Research has revealed that factors in each of five domains place older adults at increased risk for suicide-psychiatric illness, personality traits and coping styles, medical illness, life stressors and social disconnectedness, and functional impairment. Little research has examined the effectiveness of interventions to reduce the toll of suicide in older adulthood. The study of strategies to decrease suicide deaths in later life should emphasize four areas. First is approaches to early detection of older people at risk through improved understanding of multi-dimensional determinants and their interactions. Second is research on the impact of general health promotion that optimizes well-being and independent functioning for older adults on suicide outcomes. Third concerns the study of approaches to the provision of mental health care that is evidence-based, accessible, affordable, acceptable, and integrated with other aspects of care. The fourth area of high priority for research is approaches to improvement of social connectedness and its impact on suicide in older adults.


Expanding the Symbiodinium (Dinophyceae, Suessiales) Toolkit Through Protoplast Technology.
Dinoflagellates within the genus Symbiodinium are photosymbionts of many tropical reef invertebrates, including corals, making them central to the health of coral reefs. Symbiodinium have therefore gained significant research attention, though studies have been constrained by technical limitations. In particular, the generation of viable cells with their cell walls removed (termed protoplasts) has enabled a wide range of experimental techniques for bacteria, fungi, plants, and algae such as ultrastructure studies, virus infection studies, patch clamping, genetic transformation, and protoplast fusion. However, previous studies have struggled to remove the cell walls from armored dinoflagellates, potentially due to the internal placement of their cell walls. Here, we produce the first Symbiodinium protoplasts from three genetically and physiologically distinct strains via incubation with cellulase and osmotic agents. Digestion of the cell walls was verified by a lack of Calcofluor White fluorescence signal and by cell swelling in hypotonic culture medium. Fused protoplasts were also observed, motivating future investigation into intra- and inter-specific somatic hybridization of Symbiodinium. Following digestion and transfer to regeneration medium, protoplasts remained photosynthetically active, regrew cell walls, regained motility, and entered exponential growth. Generation of Symbiodinium protoplasts opens exciting, new avenues for researching these crucial symbiotic dinoflagellates, including genetic modification.


Epidermoid cyst of the spleen with CA19-9 or carcinoembryonic antigen productions: report of three cases.
True splenic cyst is a relatively rare disease, and the majority of the cases are classified as epidermoid cysts. Three cases of epidermoid cysts in the spleen or accessory spleen were studied using an immunohistochemical technique and staining for mucin. In case 1, serum carcinoembryonic antigen (CEA) and CA19-9, and in cases 2 and 3, serum CA19-9, before surgery were markedly elevated, and these levels decreased postoperatively. This strongly indicates the relationship between the increase of tumor marker levels and the presence of the epidermoid cyst. In addition, stratified squamous epithelium in the resected tissues of cases 1 and 2 was positive for anti-CEA antibody and anti-CA19-9 antibody, and that of case 3 was positive for anti-CA19-9 antibody. This strongly supports CEA or CA19-9 production in the squamous epithelium.


Purification and properties of extracellular lipase from Pseudomonas aeruginosa EF2.
Extracellular lipase was purified from a Tween 80-limited continuous culture of Pseudomonas aeruginosa EF2 by ultrafiltration of the culture supernatant followed by anion-exchange and gel-filtration FPLC. The lipase was composed of a single subunit (Mr 29,000, pI 4.9), which was capable of a variable degree of aggregation, and which exhibited both lipase activity, measured with the insoluble substrate olive oil (predominantly triolein), and esterase activity, measured with the soluble substrates p-nitrophenyl acetate and Tween 80. Lipase activity was approximately eight times higher than either type of esterase activity (kcat approximately 3000 s-1 for the hydrolysis of olive oil). The enzyme showed a marked regiospecificity for the 1,3-oleyl residues of radiolabelled triolein, was relatively stable at moderate temperatures (exhibiting a biphasic loss of activity with an initial t1/2 of 17.5 min at 60 degrees C) and was very stable to freezing and thawing. Lipase activity was only weakly inhibited by the serine-active reagent 3,4-dichloroisocoumarin, and was not inhibited by the chelating agent EDTA (1 mM). The N-terminal amino acid sequence of the Ps. aeruginosa EF2 lipase showed a marked similarity to those of several other bacterial lipases.


Plasmon-enhanced Raman spectroscopic metrics for in situ quantitative and dynamic assays of cell apoptosis and necrosis.
Apoptosis and necrosis are distinct cell death processes related to many cellular pathways. In situ, quantitatively and dynamically monitoring such processes may provide vitally important information for cell studies. However, such a method still remains elusive, even though current immunochemical methodologies have developed extremely valuable tools. Herein, we demonstrate Raman spectroscopic metrics for validating and quantifying apoptotic and necrotic cells based on their distinct molecular vibrational fingerprints. It not only allows us to quantify apoptotic and necrotic cell populations in situ in adherent cell samples, but also to be capable of continuously monitoring the dynamical processes of apoptosis and necrosis at the same time in one sample. This method provides comparable results with the "gold standard" of flow cytometry, moreover, with several incomparable advantages. Our work offers a powerful new tool for cell apoptosis and necrosis assays and is expected to become a benchmark technology in biological and medical studies.


Efficient translation initiation is required for replication of bovine viral diarrhea virus subgenomic replicons.
An internal ribosome entry site (IRES) mediates translation initiation of bovine viral diarrhea virus (BVDV) RNA. Studies have suggested that a portion of the N(pro) open reading frame (ORF) is required, although its exact function has not been defined. Here we show that a subgenomic (sg) BVDV RNA in which the NS3 ORF is preceded only by the 5' nontranslated region did not replicate to detectable levels following transfection. However, RNA synthesis and cytopathic effects were observed following serial passage in the presence of a noncytopathic helper virus. Five sg clones derived from the passaged virus contained an identical, silent substitution near the beginning of the NS3 coding sequence (G400U), as well as additional mutations. Four of the reconstructed mutant RNAs replicated in transfected cells, and in vitro translation showed increased levels of NS3 for the mutant RNAs compared to that of wild-type (wt) MetNS3. To more precisely dissect the role of these mutations, we constructed two sg derivatives: ad3.10, which contains only the G400U mutation, and ad3.7, with silent substitutions designed to minimize RNA secondary structure downstream of the initiator AUG. Both RNAs replicated and were translated in vitro to similar levels. Moreover, ad3.7 and ad3.10, but not wt MetNS3, formed toeprints downstream of the initiator AUG codon in an assay for detecting the binding of 40S ribosomal subunits and 43S ribosomal complexes to the IRES. These results suggest that a lack of stable RNA secondary structure(s), rather than a specific RNA sequence, immediately downstream of the initiator AUG is important for optimal translation initiation of pestivirus RNAs.


Global patterns of plant leaf N and P in relation to temperature and latitude.
A global data set including 5,087 observations of leaf nitrogen (N) and phosphorus (P) for 1,280 plant species at 452 sites and of associated mean climate indices demonstrates broad biogeographic patterns. In general, leaf N and P decline and the N/P ratio increases toward the equator as average temperature and growing season length increase. These patterns are similar for five dominant plant groups, coniferous trees and four angiosperm groups (grasses, herbs, shrubs, and trees). These results support the hypotheses that (i) leaf N and P increase from the tropics to the cooler and drier midlatitudes because of temperature-related plant physiological stoichiometry and biogeographical gradients in soil substrate age and then plateau or decrease at high latitudes because of cold temperature effects on biogeochemistry and (ii) the N/P ratio increases with mean temperature and toward the equator, because P is a major limiting nutrient in older tropical soils and N is the major limiting nutrient in younger temperate and high-latitude soils.


What makes mental health and substance use services youth friendly? A scoping review of literature.
There are increasing calls to make mental health and substance use services youth friendly, with hopes of improving service uptake, engagement and satisfaction. However, youth-friendliness in this area has not been clearly defined and there is a lack of information about the characteristics that make such services youth friendly. The purpose of this scoping review was to examine the literature available on youth-friendly mental health and substance use services in order to identify the characteristics, outline the expected impacts, and establish a definition. A scoping review of seven databases and grey literature sources was conducted. Twenty-eight documents were retained as relevant to the research questions. Relevant data from these documents was extracted, analyzed and presented to stakeholders, including youth, caregivers and service providers to validate and refine the results. Youth-friendly mental health and substance use services include integrated, inclusive, confidential and safe organization and policy characteristics; bright, comfortable, environment with informational materials; welcoming and genuine service providers with appropriate communication and counselling skills; an accessible location; minimal wait times; and individualized and innovative approaches. All areas in which youth friendliness should be implemented in a mental health and substance use service organization had a core value of youth voice. Improving the youth friendliness of mental health and substance use services includes incorporating youth voice in organization, policy, environment, service providers, and treatment services, and has implications for treatment uptake, engagement and satisfaction. Further research is required to determine the impact of youth friendliness in such services.


Prospective multicenter randomized phase III study of weekly versus standard docetaxel (D2) for first-line treatment of metastatic breast cancer.
Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly [75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia ≥grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to nonhematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status.


Sequential mutations associated with adaptation of human cytomegalovirus to growth in cell culture.
Mutations that occurred during adaptation of human cytomegalovirus to cell culture were monitored by isolating four strains from clinical samples, passaging them in various cell types and sequencing ten complete virus genomes from the final passages. Mutational dynamics were assessed by targeted sequencing of intermediate passages and the original clinical samples. Gene RL13 and the UL128 locus (UL128L, consisting of genes UL128, UL130 and UL131A) mutated in all strains. Mutations in RL13 occurred in fibroblast, epithelial and endothelial cells, whereas those in UL128L were limited to fibroblasts and detected later than those in RL13. In addition, a region containing genes UL145, UL144, UL142, UL141 and UL140 mutated in three strains. All strains exhibited numerous mutations in other regions of the genome, with a preponderance in parts of the inverted repeats. An investigation was carried out on the kinetic growth yields of viruses derived from selected passages that were predominantly non-mutated in RL13 and UL128L (RL13+UL128L+), or that were largely mutated in RL13 (RL13-UL128L+) or both RL13 and UL128L (RL13-UL128L-). RL13-UL128L- viruses produced greater yields of infectious progeny than RL13-UL128L+ viruses, and RL13-UL128L+ viruses produced greater yields than RL13+UL128L+ viruses. These results suggest strongly that RL13 and UL128L exert at least partially independent suppressive effects on growth in fibroblasts. As all isolates proved genetically unstable in all cell types tested, caution is advised in choosing and monitoring strains for experimental studies of vulnerable functions, particularly those involved in cell tropism, immune evasion or growth temperance.


Investigator profile. An interview with Keith Cheng, M.D., Ph.D. Interview by Vicki Glaser.
Dr. Cheng is Associate Professor of Pathology, of Biochemistry & Molecular Biology, and of Pharmacology in the Jake Gittlen Cancer Research Foundation at the Penn State College of Medicine. He received a Bachelor's degree in Biochemical Sciences from Harvard University and an M.D. from New York University School of Medicine. He trained in Anatomic Pathology at Brigham & Women's Hospital in Boston and University of Washington, and while engaged in the latter, earned a Ph.D. in phage genetics at the Fred Hutchinson Cancer Research Institute and the University of Washington in Seattle. During his postdoctoral training at the University of Washington, Dr. Cheng studied mechanisms of mutation.


Effect of non-perforating abomasal lesions on reproductive performance, milk yield and carcass weight at slaughter in Danish Holstein cows.
Non-perforating abomasal lesions are common in Danish Holstein cows, but the impact on production has not been studied. Our objective was to compare milk yield, carcass weight, days to first service and initiation of breeding among cows with different non- perforating abomasal lesion types and locations to cows with no such lesions. The occurrence, type and localisation of non- perforating abomasal lesions were characterised at slaughter in Danish Holstein cows, and first insemination dates (n = 592), milk yield (n = 999) and carcass information (n = 1,317) was also available. Production and reproduction data were retrieved from all other cows from the herds of origin. This information was used to evaluate the expected production performance in the herds. Of the 1,317 cows investigated at slaughter, 572, 428, 677, and 91 cows had at least one lesion Subtype 1a (mucosal erosion), 1b (acute deeper lesion), 1c (chronic deeper lesion) or 1d (scarring following a lesion), respectively. Cows with lesion Subtype 1c and lesions in the pyloric part of the abomasum were generally found to be culled later in lactation than their herd mates. Milk yield and days to first service were not associated with any lesion types. The occurrence of lesion Subtype 1c and lesions in the pylorus were associated with a higher weight at slaughter compared to cows without lesions of this subtype or in this location. Most Subtype 1c lesions was found in the pylorus. Initiation of breeding before 150 days in milk was positively associated with the number of lesions in the corpus of the abomasum. We discovered two sources of selection bias. First, cows with lesions had a higher carcass weight but also remained in the herds for longer after calving than cows without lesions. This would give them more time to overcome the period of negative energy balance in early lactation. Second, although the causes of culling were not known, cows with no lesions generally had a relatively low milk yield and could have been culled for this reason.". While non- perforating abomasal ulcers may have an effect on the production and reproduction data, the observational data presented show no evidence of such a relationship. It may be necessary to employ other study designs to identify any effects that might exist, but if the relationship cannot be demonstrated in a dataset of this magnitude, it is not deemed to be of practical relevance.


Skin-Penetrating Interfaces for Millimeter-Wave Non-Invasive Glucose Concentration Estimation: Numerical Analysis.
Millimeter-wave (MMW) glucose concentration estimation possesses a great advantage of non-invasiveness. The long history of investigation, however, has not yet reached practical applications because of its insufficient accuracy and stability. To solve these problems, this paper proposes two high skin-penetration interfaces, which we name equivalent quarter-wavelength interface and equivalent Brewster's-angle interface. We analyze their scattering characteristics in a frequency range of 60 - 90 GHz. Analysis results show that both the interfaces suppress the body-surface scattering, allowing the MMWs to penetrate through body surface into tissues to extract information on blood-glucose concentration with higher sensitivity, e.g., with 147-times enhancement of phase changes. These interfaces can be an important step toward realizing non-invasive blood glucose concentration estimation.


Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.
We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.


Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin.
Orexins are involved in the central nervous control of appetite and behavior, and in addition, they are present in endocrine cells and/or neurons in the intestine. The role of these peptides in peripheral regulation of intestinal secretion has not been investigated. We thus compared the effects of orexin A and some established secretagogues on duodenal HCO3- secretion in fed rats with effects in rats exposed to short (overnight) food deprivation. Rats were anesthetized with thiobarbiturate, a 12-mm segment of proximal duodenum with intact blood supply was cannulated in situ, and the alkaline secretion was titrated by pH stat. Secretagogues were supplied specifically to the duodenum by close intra-arterial infusion. Orexin A (60-600 pmol x kg(-1) x h(-1)) caused marked and dose-dependent stimulation of the duodenal secretion in fed animals but did not affect secretion in overnight food-deprived animals. Similarly, short fasting caused a 100-fold increase in the amount of the muscarinic agonist bethanechol (from 50 to 5,000 nmol x kg(-1) x h(-1)) required for stimulation of the secretion. In contrast, the secretory responses to VIP (50-1,000 pmol x kg(-1) x h(-1)) and melatonin (20-200 nmol x kg(-1) x h(-1)) were not affected. The appetite-regulating peptide orexin A is thus a stimulant of intestinal secretion, but the response to this peptide as well as the muscarinic agonist bethanechol is markedly dependent on previous intake of food. Overnight fasting is a standard experimental procedure in studies of gastrointestinal function and pathophysiology in humans and animals. Studies made on neuroendocrine control of intestinal secretion may require reevaluation with respect to feeding status.


Construction of detubularized ileal neobladder after radical cystoprostatectomy.
In an attempt to improve the patient's quality of life, we performed construction of neobladder using detubularized ileum along with radical cystoprostatectomy in 3 male patients with invasive bladder cancer. The mean followup was 28.3 months (16-45 months). All 3 patients achieved continent urination through the natural urine pathway-urethra with a satisfactory urinary stream during the day, but only 2 of them could also obtain continence in the night. Urodynamic study of the ileal neobladder showed a low pressure (mean 15.3 cm water) and no involuntary pressure spikes in the neobladder. The maximal urethral closure pressure (mean 62.0 cm water) and functional profile length (mean 3.0 cm) were adequate. In addition, the maximal uroflow rate was good (mean 16.7 ml/sec). There was no reflux in any of our patients. The radionuclide renal function study revealed that the renal function was preserved after operation in all 3 patients. Neocystourethroscopy showed no tumor and no stricture at the ileourethral anastomotic site in our 3 patients. There was no complication related to the operation. No disturbances of nutrition or electrolytes were found in any patient. All 3 patients had a satisfactory quality of life after operation though one patient died of widespread metastasis 16 months after operation. In conclusion, construction of detubularized ileal neobladder may be one of the ideal surgical procedures for bladder substitution after radical cystoprostatectomy.


The exquisite structure and reaction mechanism of bacterial Pz-peptidase A toward collagenous peptides: X-ray crystallographic structure analysis of PZ-peptidase a reveals differences from mammalian thimet oligopeptidase.
Pz-peptidase A, from the thermophilic bacterium Geobacillus collagenovorans MO-1, hydrolyzes a synthetic peptide substrate, 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-PLGPR), which contains a collagen-specific tripeptide sequence, -Gly-Pro-X-, but does not act on collagen proteins themselves. The mammalian enzyme, thimet oligopeptidase (TOP), which has comparable functions with bacterial Pz-peptidases but limited identity at the primary sequence level, has recently been subjected to x-ray crystallographic analysis; however, no crystal structure has yet been reported for complexes of TOP with substrate analogues. Here, we report crystallization of recombinant Pz-peptidase A in complex with two phosphinic peptide inhibitors (PPIs) that also function as inhibitors of TOP and determination of the crystal structure of these complexes at 1.80-2.00 Å resolution. The most striking difference between Pz-peptidase A and TOP is that there is no channel running the length of bacterial protein. Whereas the structure of TOP resembles an open bivalve, that of Pz-peptidase A is closed and globular. This suggests that collagenous peptide substrates enter the tunnel at the top gateway of the closed Pz-peptidase A molecule, and reactant peptides are released from the bottom gateway after cleavage at the active site located in the center of the tunnel. One of the two PPIs, PPI-2, which contains the collagen-specific sequence, helped to clarify the exquisite structure and reaction mechanism of Pz-peptidase A toward collagenous peptides. This study describes the mode of substrate binding and its implication for the mammalian enzymes.


Fabrication of arrays of metal and metal oxide nanotubes by shadow evaporation.
This paper describes a simple technique for fabricating uniform arrays of metal and metal oxide nanotubes with controlled heights and diameters. The technique involves depositing material onto an anodized aluminum oxide (AAO) membrane template using a collimated electron beam evaporation source. The evaporating material enters the porous openings of the AAO membrane and deposits onto the walls of the pores. The membrane is tilted with respect to the column of evaporating material, so the shadows cast by the openings of the pores onto the inside walls of the pores define the geometry of the tubes. Rotation of the membrane during evaporation ensures uniform deposition inside the pores. After evaporation, dissolution of the AAO in base easily removes the template to yield an array of nanotubes connected by a thin backing of the same metal or metal oxide. The diameter of the pores dictates the diameter of the tubes, and the incident angle of evaporation determines the height of the tubes. Tubes up to approximately 1.5 mum in height and 20-200 nm in diameter were fabricated. This method is adaptable to any material that can be vapor-deposited, including indium-tin oxide (ITO), a conductive, transparent material that is useful for many opto-electronic applications. An array of gold nanotubes produced by this technique served as a substrate for surface-enhanced Raman spectroscopy: the Raman signal (per molecule) from a monolayer of benzenethiolate was a factor of approximately 5 x 10(5) greater than that obtained using bulk liquid benzenethiol.


The magnetic order of GdMn₂Ge₂ studied by neutron diffraction and x-ray resonant magnetic scattering.
The magnetic structure of GdMn₂Ge₂ (tetragonal I4/mmm) has been studied by hot neutron powder diffraction and x-ray resonant magnetic scattering techniques. These measurements, along with the results of bulk experiments, confirm the collinear ferrimagnetic structure with moment direction parallel to the c-axis below T(C) = 96 K and the collinear antiferromagnetic phase in the temperature region T(C) < T < T(N) = 365 K. In the antiferromagnetic phase, x-ray resonant magnetic scattering has been detected at Mn K and Gd L₂ absorption edges. The Gd contribution is a result of an induced Gd 5d electron polarization caused by the antiferromagnetic order of Mn-moments.


Crohn's disease: evidence for involvement of unregulated transcytosis in disease etio-pathogenesis.
Crohn's disease (CD) is a chronic inflammatory bowel disease. Research has identified genetic predisposition and environmental factors as key elements in the development of the disease. However, the precise mechanism that initiates immune activation remains undefined. One pathway for luminal antigenic molecules to enter the sterile lamina propria and activate an immune response is via transcytosis. Transcytosis, although tightly regulated by the cell, has the potential for transepithelial transport of bacteria and highly antigenic luminal molecules whose uncontrolled translocation into the lamina propria can be the source of immune activation. Viewed as a whole, the evidence suggests that unregulated intestinal epithelial transcytosis is involved in the inappropriate presentation of immunogenic luminal macromolecules to the intestinal lamina propria. Thus fulfilling the role of an early pre-morbid mechanism that can result in antigenic overload of the lamina propria and initiate an immune response culminating in chronic inflammation characteristic of this disease. It is the aim of this paper to present evidence implicating enterocyte transcytosis in the early etio-pathogenesis of CD.


A quantitative assessment of primary and secondary immune responses in cattle using a B cell ELISPOT assay.
The aim of the study was to build a comprehensive picture of the appearance in the blood stream of Ag-specific plasma cells and memory B cells in the bovine model. For this purpose, we have developed a method allowing the detection and quantification of both cell types within individual calves immunised with ovalbumin. During the primary response, we detected a burst of ovalbumin-specific plasma cells at days 6 and 7 post-immunisation, which was followed by the production of specific Ab, whereas a gradual increase of memory B cells was only detected from day 15. As expected, a boost immunisation performed 7 weeks later induced a quicker and stronger secondary response. Indeed, a burst of plasma cells was detected in the blood at days 3 and 4, which was followed by a strong increase in Ab titres. Furthermore, a burst of memory B cells, and not a gradual increase, was detected at days 5 and 6 post-boost immunisation. Importantly, we showed a strong correlation between the anti-ovalbumin-specific IgG titres detected 5 months after secondary immunisation and the plasma cell numbers detected in the blood at the peak response after secondary immunisation. The detection and quantification of plasma cells following an mmunisation/vaccination strategy could constitute a very effective means for predicting the magnitude and longevity of an Ab response.


A comparison of ICU mortality prediction using the APACHE II scoring system and artificial neural networks.
The aim of this study was to compare the ability of artificial neural networks and the Acute Physiology and Chronic Health Evaluation II score to predict mortality in adult intensive care units. The same physiological variables were used in both predictive models to predict hospital mortality from a data set of 8796 patients collected from 26 adult intensive care units in the United Kingdom and Ireland as part of the Intensive Care Society study. The results from the two models were compared with the actual outcome. The overall prediction accuracy and the overall goodness-of-fit of all the models were assessed. Both predictive models showed similar goodness-of-fit and prediction discrimination. The overall predictive and classification performance of the artificial neural network developed matched and in some aspects was better than that of Acute Physiology and Chronic Health Evaluation II.


[Kinetics of hepatotropic radiopharmaceuticals].
A study was made of the biological distribution of 131I labeled stains and 99mTc labeled iminodiacetic acid derivatives in 153 patients of whom 98 suffered from jaundice of different genesis. Significant differences of their behavior in the human body depending on the chemical structure of the compound were revealed. Blood clearance for the iminodiacetic acid derivatives was 1.5-2 times as high as compared to that for the labeled stains. The rate of transit via the hepatocyte was the highest in 99mTc-MESIDA (USSR) 99mTc-DIDA and 99mTc-TIDA. The rate and volume of the renal excretion of the radiopharmaceutical depended on the main substance molecular structure. Retarded blood clearance lowered excretion of the radiopharmaceuticals by the liver and their considerable excretion with urine were observed. The Soviet radiopharmaceuticals 99mTc-MESIDA and 99mTc-BUTILIDA by their pharmacokinetic characteristics and quality were in no way inferior to the best foreign analogs.


Knee Arthroscopy for the Treatment of Lipoma Arborescens: A Systematic Review of the Literature.
Lipoma arborescens is a rare, intra-articular benign lesion characterized by hyperplastic formation of villous projections that commonly presents as nonspecific mechanical knee pain. The treatment of choice for lipoma arborescens of the knee is open or arthroscopic synovectomy. However, data are lacking on the success of arthroscopic treatment, despite its increasingly widespread use. We aimed to systemically review the outcomes of arthroscopic treatment of lipoma arborescens. PubMed and Embase were searched by 2 reviewers independently on October 9, 2018, and all relevant articles in the English and French languages up to and including that date were considered. The search terms "lipoma arborescens," "knee," "arthroscopy," and "arthroscopic" were used. Articles were screened on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Among the 110 initial studies that were retrieved, 28 satisfied the inclusion criteria. A total of 71 knees in 65 patients ranging from 13 to 78 years of age underwent arthroscopic synovectomy for the treatment of lipoma arborescens. The duration of follow-up ranged from 3 weeks to 84 months. The recurrence rate was 2.8%, and 2 patients underwent conversion to open surgery. One patient had postoperative hematoma that required evacuation, and another patient reported persistent residual pain at the time of the latest follow-up. On the basis of this uncontrolled, systematic review, arthroscopic synovectomy is a safe and effective treatment for lipoma arborescens of the knee, with a success rate of >95%. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Expression of cancer stem cell markers in pancreatic intraepithelial neoplasias and pancreatic ductal adenocarcinomas.
Cancer stem cells (CSCs) play pivotal roles in cancer growth, invasion, metastasis and recurrence. Several proteins have been reported as CSC markers for pancreatic ductal adenocarcinoma (PDAC). In the present study, we examined the correlation between pancreatic intraepithelial neoplasias (PanINs) and CSC markers including CD24, CD44, CD133, CXCR4, ESA and nestin using immunohistochemical analysis. Furthermore, we examined the roles and clinical significance of these CSC markers in PDAC. CD24-, CD44-, CXCR4-, ESA- and nestin-positive cells were detected in the following tissues, listed in order of increasing percentage: normal ducts < low-grade PanINs < high-grade PanINs < PDACs. CD133 did not increase according to the malignancy grade. In PDAC, cells positive for each of the following CSC markers were detected, listed according to increasing percentage: nestin < CD133 < CD44 < CD24 < CXCR4 < ESA. CXCR4 and ESA expression correlated with well-differentiated PDAC. Venous invasion was positively associated with CD133 and inversely associated with ESA. CSC marker expression levels detected in PDAC cell lines using flow cytometry showed lowest expression of CD133 and highest of CD44, differing from the results obtained using immunohistochemistry. In two PDAC subtypes, adenosquamous carcinoma and anaplastic carcinoma, ESA was expressed more abundantly in adenocarcinoma components, whereas CD44 and nestin showed high expression in anaplastic components. Together, these results suggest that most CSC markers correlate with pancreatic carcinogenesis through the PanIN-to-PDAC sequence. Each CSC marker was related in a different manner with proliferation, differentiation, invasiveness or tissue type of PDAC.


[Unexpected back pain in the elderly ankylosing spondylitis patient].
A 63-year-old man with ankylosing spondylitis (AS) presented with persistent pain in his back after minor trauma. Radiographs revealed no acute pathology. Six weeks later an MRI scan was performed which showed a vertebral fracture at level Tiii with kyphotic deformity. Another 63-year-old male AS patient presented with back pain after minor trauma 10 days before presentation. At plain radiology a vertebral fracture of Tx was discovered. A third patient, an 83-year-old male AS patient complained about back pain after minor trauma; CT imaging revealed a Tx vertebral fracture. All three patients underwent surgical fixation and were discharged without major complications. In principle, an older patient with an established AS complaining of back pain must be regarded as having a fracture of the vertebral column until the contrary is proven, even in the absence of any recent history of trauma. This strategy can prevent major complication in these patients.


Tetrandrine inhibits Ca2+ release-activated Ca2+ channels in vascular endothelial cells.
The effects of tetrandrine (TET), a Ca2+ antagonist of bis-benzylisoquinoline alkaloid origin, on cultured single bovine pulmonary artery endothelial cells were examined using fluorescence ratio imaging and whole-cell attached patch-clamp techniques. Thapsigargin (TSG, 100 nM), a selective endoplasmic reticulum Ca2+-ATPase pump inhibitor known to induce the release of nitric oxide (NO) from vascular endothelial cells via a Ca2+-dependent manner, caused a rapid elevation of cytosolic Ca2+ concentration, which was inhibited by 30 microM TET. In whole-cell patch-clamp study using the same vascular endothelial cells, addition of 100 nM TSG caused a significant enhancement of depolarization-evoked Ca2+-dependent, outward K+ currents, which could also be abolished by 30 microM TET. The present results demonstrate directly that TET, in addition to its known inhibitory effects on vascular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhibits NO production by the endothelial cells through blockade of Ca2+ release-activated Ca2+ channels.


Temporal corneal phacoemulsification in filtered glaucoma patients.
To evaluate the effect of temporal clear corneal phacoemulsification on intraocular pressure (IOP) in eyes that had prior trabeculectomy. Retrospective case-control study. Forty consecutive patients (cases; TRAB-PHACO group) who underwent temporal corneal phacoemulsification subsequent to trabeculectomy were identified. Forty patients (controls; TRAB group) who had trabeculectomy alone were matched to the cases for length of follow-up, age, IOP, number of anti-glaucoma medications, number of 5-fluorouracil (5-FU) injections, race, sex and diagnosis. Comparison of IOP before and one year after phacoemulsification in the TRAB-PHACO group, and comparison with the TRAB group. Survival analysis of IOP control after trabeculectomy in the TRAB-PHACO and TRAB groups. In the TRAB-PHACO group, IOP one year after phacoemulsification was not significantly different from the pre-phacoemulsification IOP value (p = 0.65). Kaplan-Meier survival analysis showed that the rates of IOP control at 3, 6 and 9 years after trabeculectomy in the TRAB-PHACO group were 80%, 66% and 44%; in the TRAB group these were 79%, 69% and 55%. These survival curves were not statistically different (p = 0.55). Cataract surgery by temporal clear corneal phacoemulsification in eyes with filtering blebs after trabeculectomy does not adversely affect long term IOP control.


[2D imaging simulations of a small animal PET scanner with DOI measurement: jPET-RD.].
We present a preliminary study on the design of a high sensitivity small animal DOI-PET scanner: jPET-RD (for Rodents with DOI detectors), which will contribute to molecular imaging. The 4-layer DOI block detector for the jPET-RD that consists of scintillation crystals (1.4 mm x 1.4 mm x 4.5 mm) and a flat panel position-sensitive photomultiplier tube (52 mm x 52 mm) was previously proposed. In this paper, we investigate imaging performance of the jPET-RD through numerical simulations. The scanner has a hexagonal geometry with a small diameter and a large axial aperture. Therefore DOI information is expected to improve resolution uniformity in the whole field of view (FOV). We simulate the scanner for various parameters of the number of DOI channels and the crystal length. Simulated data are reconstructed using the maximum likelihood expectation maximization with accurate system modeling. The trade-off results between background noise and spatial resolution show that only shortening the length of crystal does not improve the trade-off at all, and that 4-layer DOI information improves uniformity of spatial resolution in the whole FOV. Excellent performance of the jPET-RD can be expected based on the numerical simulation results.


Isochromosome (X)(p10) in hematologic disorders: FISH study of 14 new cases show three types of centromere signal patterns.
Though X chromosome anomalies are uncommon in hematologic malignancies, isodicentric X chromosomes, idic(X)(q13), with break and fusion points at Xq13 are well known among older females with de novo myelodysplasia. In contrast, only 17 patients with X isochromosomes involving break and fusion points at the centromere i(X)(p10) have been published, to our knowledge. We present 14 new patients with i(X)(p10) identified by G-banding and further characterized by fluorescence in situ hybridization (FISH) using probes for the X p-arm, X alpha-satellite DNA (DXZ1), and the XIST gene (Xq13). These anomalies each had an X p-arm probe signal on either side of a single centromeric FISH signal, thus they are monocentric isochromosomes. On the basis of FISH, the following three centromeric patterns were identified: (1) centromere signal same size as normal X, (2) centromere signal larger than normal X, and (3) centromere signal smaller than normal X. These centromere patterns may be related to the mechanism of i(X)(p10) formation. In 9 (64%) of 14 patients, the i(X)(p10) was the sole anomaly, attesting to its pathogenic potential. Our series, when collated with information on previously reported cases of i(X)(p10), show that this anomaly is associated with females with a median age 74 years, though patients from 3.75 to 49 years, including a 17-year-old in the present cohort, have been described. i(X)(p10) is observed in a wide range of hematologic malignancies, including myeloid and lymphoid disorders, as well as a patient with therapy-related AML in the present series. i(X)(p10) has been reported in occasional males, indicating that this anomaly can arise from active X chromosomes. It is not known whether i(X)(p10) arises randomly from the active or inactive X chromosome in female patients.


[Morphogenetic potentials of the enterochromaffin cells in tumor growth].
The structure of 69 argentaffine-cell serotonin-producing carcinoids was studied. The concentration of cells which display the morphofunctional characteristics of enterochromaffin cells was found to vary within a wide range: from constituting the bulk of cell element population to few or even solitary cells. The variegated histological patterns observed in carcinoids suggest different types of secretion of EC-cells; para-, endo- and sometimes-exocrine secretion. Tumor cells produce amines and polypeptide hormones. The functional significance of lipids frequently identified in carcinoids remains to be established. Since endocrine cells at different stages of differentiation and mucus-producing ones occur in the same tumors, it is suggested that both originate from the cambial elements of the epithelial lining of mucous membranes.


In vitro and in vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene.
It has been well established that bone morphogenetic protein-2 (BMP-2) can induce bone formation both in vivo and in vitro, although high concentrations (up to milligrams) of BMP-2 have been required to achieve this effect in vivo. Further, clinical applications are usually limited to a single dose at the time of implantation. In an attempt to prolong the transforming effect of BMP-2 we used a recombinant adenoviral vector carrying the human BMP-2 gene (Adv-BMP2) to transduce marrow-derived mesenchymal stem cells (MSC) of skeletally mature male New Zealand white rabbits. The pluripotential MSC were incubated with Adv-BMP2 overnight followed by culture in growth medium for 1 week. Assays on tissue cultures demonstrated that these Adv-BMP2 transduced MSC produced BMP-2 protein, differentiated into an osteoprogenitor line, and induced bone formation in vitro. These MSC had increased alkaline phosphatase activity, increased expression of type I collagen, osteopontin, and osteocalcin mRNA, and induced matrix mineralization compared with both non-transduced cells and cells transduced with a control adenoviral construct. To analyze the osteogenic potential in vivo, Adv-BMP2-transduced MSC were autologously implanted into the intertransverse process space between L5 and L6 of the donor rabbits. The production of new bone was demonstrated by radiographic examination 4 weeks later in areas implanted with cells transduced with Adv-BMP2, whereas no bone was evident at sites implanted with cells transduced with the control adenoviral construct. Histological examination further confirmed the presence of new bone formation. These accumulated data indicate that it is possible to successfully transduce mesenchymal stem cells with a recombinant adenoviral vector carrying the gene for BMP-2 such that these cells will produce BMP-2, differentiate into an osteoprogenitor line, and induce bone formation both in vitro and in vivo. Moreover, incubation of the Adv-BMP2-transduced cells for an additional 7 days in culture before transplantation enhances the success rate in bone formation (three out of three) as compared with our previous report (one out of five, Calcif Tissue Int 63:357-360, 1998).


Iodine biokinetics and radioiodine exposure after recombinant human thyrotropin-assisted remnant ablation in comparison with thyroid hormone withdrawal.
A few prospective studies have evaluated the use of recombinant human TSH (rhTSH) for radioiodine remnant ablation. Our objective was to compare the effects of the both TSH regimens on iodine biokinetics in the thyroid remnant, dosimetry, and radiation protection. We conducted a prospective randomized study. Eighty-eight patients were enrolled for radioiodine ablation to either the hypothyroid or rhTSH arms. A whole-body scan was performed at 48 and 144 h after therapy. Dose rates were assessed at 24, 48, and 144 h. Urinary samples were obtained during the first 48 h. Thyroglobulin was assessed before and after therapy. Iodine biokinetics in the remnants were calculated from gamma-count rates. Radiation-absorbed dose was calculated using OLINDA software. Exposure estimation was based on a validated model. The effective half-life in the remnant thyroid tissue was significantly longer after rhTSH than during hypothyroidism (P = 0.01), whereas 48-h (131)I uptakes and residence times were similar. After therapy, thyroglobulin release (a marker of cell damage) was lower in the rhTSH arm. The mean total-body effective half-life and residence time were shorter in patients treated after rhTSH. Residence time was also lower for the colon and stomach. Absorbed dose estimates were lower in the rhTSH arm for the lower large intestine, breasts, ovaries, and the bone marrow. Dose rates at the time of discharge were lower in the rhTSH group with a reduction in cumulative radiation exposure to contact persons. In comparison with thyroid hormone withdrawal, rhTSH is associated with longer remnant half-life of radioactive iodine while also reducing radiation exposure to the rest of the body and also to the general public who come in contact with such patients.


Intracranial glioma xenograft model rapidly reestablishes blood-brain barrier integrity for longitudinal imaging of tumor progression using fluorescence molecular tomography and contrast agents.
The blood-brain barrier (BBB) is a major obstacle to detecting and treating brain tumors. Overcoming this challenge will facilitate the early and accurate detection of brain lesions and guide surgical resection of tumors. We generated an orthotopic brain tumor model that simulates the pathophysiology of gliomas at early stages; determine the BBB integrity and breakdown over the time course of tumor progression using generic and cancer-targeted near-infrared (NIR) fluorescent molecular probes. We developed an intracranial tumor xenograft model that rapidly reestablished BBB integrity and monitored tumor progression by bioluminescence imaging. Sham control mice were injected with phosphate-buffered saline only. Fluorescence molecular tomography (FMT) was used to quantify the uptake of tumor-targeted and passive NIR fluorescent imaging agents in orthotopic glioma (U87-GL-GFP PDE7B H217Q cells) tumor model. Cancer-induced and transient (with focused ultrasound, FUS) disruption of BBB integrity was monitored with NIR fluorescent dyes. Stereotactic injection of 50,000 cells into mouse brain allowed rapid reestablishment of BBB integrity within a week, as determined by the inability of both tumor-targeted and generic NIR imaging agents to extravasate into the brain. Tumor-induced BBB disruption was observed 7 weeks after tumor implantation. FUS achieved a similar effect at any time point after reestablishing BBB integrity. While tumor uptake and retention of the passive NIR dye, indocyanine green, was negligible, both actively tumor-targeting agents exhibited selective accumulation in the tumor region. The tumor-targeting molecular probe that clears rapidly from nontumor brain tissue exhibits higher contrast than the analogous vascular-targeting agent and helps delineate tumors from sham control. We highlight the utility of FMT imaging for longitudinal assessment of brain tumors and the interplay between the stages of BBB disruption and molecular probe retention in tumors, with potential application to other neurological diseases.


Cardiac natriuretic peptides--hope or hype?
In recent years, biomedical science has witnessed the emergence of peptide biochemicals as significant topics of research. Some of these peptides are of little potential clinical use, while others, of which cardiac natriuretic peptides are an example, appear to be promising. This particular group of peptides (i.e. ANP, BNP and CNP) shows promising diagnostic as well as therapeutic potential for various pathological conditions. In the case of acute myocardial infarction, these peptides have significant diagnostic and predictive properties, more so than other biochemicals such as adrenaline, renin and aldosterone. In addition, ANP is found to have significant benefits over the classical anti-anginal drug glyceryl trinitrate. However, as is the case with other peptides, applying these benefits clinically may not be easy because of the structure of the compounds, but various strategies are now being applied to solve this problem. These include the use of non-peptide receptor ligands, inhibitors of ANP metabolism, gene therapy and so on. The development of drugs in clinical practice, which exploits the natriuretic peptides system therefore seems to be promising, and this article reviews advances in our understanding of these compounds.


NK Cells Expressing a Chimeric Activating Receptor Eliminate MDSCs and Rescue Impaired CAR-T Cell Activity against Solid Tumors.
Solid tumors are refractory to cellular immunotherapies in part because they contain suppressive immune effectors such as myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic lymphocytes. Strategies to reverse the suppressive tumor microenvironment (TME) should also attract and activate immune effectors with antitumor activity. To address this need, we developed gene-modified natural killer (NK) cells bearing a chimeric receptor in which the activating receptor NKG2D is fused to the cytotoxic ζ-chain of the T-cell receptor (NKG2D.ζ). NKG2D.ζ-NK cells target MDSCs, which overexpress NKG2D ligands within the TME. We examined the ability of NKG2D.ζ-NK cells to eliminate MDSCs in a xenograft TME model and improve the antitumor function of tumor-directed chimeric antigen receptor (CAR)-modified T cells. We show that NKG2D.ζ-NK cells are cytotoxic against MDSCs, but spare NKG2D ligand-expressing normal tissues. NKG2D.ζ-NK cells, but not unmodified NK cells, secrete proinflammatory cytokines and chemokines in response to MDSCs at the tumor site and improve infiltration and antitumor activity of subsequently infused CAR-T cells, even in tumors for which an immunosuppressive TME is an impediment to treatment. Unlike endogenous NKG2D, NKG2D.ζ is not susceptible to TME-mediated downmodulation and thus maintains its function even within suppressive microenvironments. As clinical confirmation, NKG2D.ζ-NK cells generated from patients with neuroblastoma killed autologous intratumoral MDSCs capable of suppressing CAR-T function. A combination therapy for solid tumors that includes both NKG2D.ζ-NK cells and CAR-T cells may improve responses over therapies based on CAR-T cells alone.


Painful soft-tissue reaction to injectable Norian SRS calcium phosphate cement after curettage of enchondromas.
A prospective single-cohort study was designed to include 20 patients with enchondromas but was stopped because of poor early results. Four patients with an enchondroma, three in the proximal humerus and one in the distal femur, were treated by curettage and filling of the defect with Norian SRS cement. Clinical and radiological follow-up including CT and MRI was carried out for 18 months. All three patients with lesions in the proximal humerus had severe pain and limited movement of the shoulder. The radiological and CT appearances of the cement were unchanged at follow-up. There were characteristic appearances of synovitis and periosteitis on MRI in two patients. Since the cement induces a soft-tissue reaction the bony cavity should be sealed with the curetted and burred bone after curettage and introduction of Norian cement, especially in sites where a tourniquet cannot be applied.


[Essential fatty acids in cardiovascular physiopathology].
Numerous studies have shown that a limitation of dietary saturated fatty acids and cholesterol associated with an increase in linoleic acid consumption lowers high blood cholesterol level (a risk factor in the development of atherosclerosis). Besides the importance of dietary fatty acid composition in determining blood lipoprotein concentrations, it has been shown that increased intake of dietary linoleic acid influences arterial thrombosis tendency in rats and improves blood platelet function in man. Linoleic acid rich diets also loffer arterial blood pressure in salt loaded rats and in hypertensive men. Moreover, these diets improve heart function in rats as measured by coronary perfusion rate and ventricular work. These favourable effects of linoleic acid on various risk factors of cardiovascular diseases are observed at dietary levels which largely exceed the minimum amount required to prevent or cure the essential fatty acid deficiency syndrome. It is evident that the study of the physiological effects of linoleic acid goes beyond the scope of this syndrome. Essential fatty acids have structural functions as integral part of membrane phospholipids and dynamic functions as precursors of prostaglandins. On account of their structural function, the essential fatty acids influence the fluidity of biomembranes and the activity of membrane-bound enzymes and receptor systems. Certain physiological effects of dietary linoleic acid would be explained via this mechanism. Moreover linoleic acid is known to regulate the endogenous prostaglandin biosynthesis. Though incomplete, the knowledge gained fully justifies the application of preventive measures proposed by numerous expert committees for groups of populations with a high rate of atherosclerosis.


[Assessment of caries activity and caries risk].
This paper reviews the present knowledge regarding methods of caries prediction. The clinician's ability to predict caries by examination and on the basis of knowledge of patient's attitude and background functions relatively well. Bacterial and salivary tests do not contribute significantly to this. The caries present at the moment of examination, the cariesexperience, is the best predictor of caries among children.


Health workforce planning: an analysis of employer demand pertaining to the Victorian medical record administration & diagnostic coding workforces.
In 1990, LaTrobe University introduced the world's first Post-Graduate Diploma in Nosology, in response to unmet demand for diagnostic coders in Victoria. After the first graduates entered employment, a two-part study was undertaken. The composition, employment levels and projected institutional demand for the coding workforce (comprising medical record administrator coders, Nosologists and "unqualified" coders) were ascertained. In parallel, the current employment levels and projected demand for the institutional medical record administrator workforce also were investigated. The institutional variables of major health care role, annual inpatient discharges and operating sector were found to impact upon employment levels and demand for both workforces by current, prospective and non-employers. The study identified a minimal projected demand for nosologists, the reasons for which are postulated, and negligible projected demand for nonqualified coding personnel. The results highlight a health current and projected employer demand for both medical record administrators and medical record administrator coders.


Exploring the role of the left DLPFC in fatigue during unresisted rhythmic movements.
Understanding central fatigue during motor activities is important in neuroscience and different medical fields. The central mechanisms of motor fatigue are known in depth for isometric muscle contractions; however, current knowledge about rhythmic movements and central fatigue is rather scarce. In this study, we explored the role of an executive area (left dorsolateral prefrontal cortex [DLPFC]) in fatigue development during rhythmic movement execution, finger tapping (FT) at the maximal rate, and fatigue after effects on the stability of rhythmic patterns. Participants (n = 19) performed six sets of unresisted FT (with a 3 min rest in-between). Each set included four interleaved 30 s repetitions of self-selected (two repetitions) and maximal rate FT (two repetitions) without rest in-between. Left DLPFC involvement in the task was perturbed by transcranial static magnetic stimulation (tSMS) in two sessions (one real and one sham). Moreover, half of the self-selected FT repetitions were performed concurrently with a demanding cognitive task, the Stroop test. Compared with sham stimulation, real tSMS stimulation prevented waning in tapping frequency at the maximal rate without affecting perceived levels of fatigue. Participants' engagement in the Stroop test just prior to maximal FT reduced the movement amplitude during this mode of execution. Movement variability at self-selected rates increased during Stroop execution, especially under fatigue previously induced by maximal FT. Our results indicate cognitive-motor interactions and a prominent role of the prefrontal cortex in fatigue and the motor control of simple repetitive movement patterns. We suggest the need to approach motor fatigue including cognitive perspectives.


Burkitt lymphoma research in East Africa: highlights from the 9(th) African organization for research and training in cancer conference held in Durban, South Africa in 2013.
A one-day workshop on Burkitt lymphoma (BL) was held at the 9(th) African Organization for Research and Training in Cancer (AORTIC) conference in 2013 in Durban, South Africa. The workshop featured 15 plenary talks by delegates representing 13 institutions that either fund or implement research on BL targeting AORTIC delegates primarily interested in pediatric oncology. The main outcomes of the meeting were improved sharing of knowledge and experience about ongoing epidemiologic BL research, BL treatment in different settings, the role of cancer registries in cancer research, and opportunities for African scientists to publish in scientific journals. The idea of forming a consortium of BL to improve coordination, information sharing, accelerate discovery, dissemination, and translation of knowledge and to build capacity, while reducing redundant efforts was discussed. Here, we summarize the presentations and discussions from the workshop.


Regulation of endothelial nitric oxide synthase and high-density lipoprotein quality by estradiol in cardiovascular pathology.
Estrogens have been recognized, in the last 3 decades, as important hormones in direct and indirect modulation of vascular health. In addition to their direct benefit on cardiovascular health, the presence of esterified estrogen in the lipid core of high-density lipoprotein (HDL) particles indirectly contributes to atheroprotection by significantly improving HDL quality and functionality. Estrogens modulate their physiological activity via genomic and nongenomic mechanisms. Genomic mechanisms are thought to be mediated directly by interaction of the hormone receptor complex with the hormone response elements that regulate gene expression. Nongenomic mechanisms are thought to occur via interaction of the estrogen with membrane-bound receptors, which rapidly activate intracellular signaling without binding of the hormone receptor complex to its hormone response elements. Estradiol in particular mediates early and late endothelial nitric oxide synthase (eNOS) activation via interaction with estrogen receptors through both nongenomic and genomic mechanisms. In the vascular system, the primary endogenous source of nitric oxide (NO) generation is eNOS. Nitric oxide primarily influences blood vessel relaxation, the heart rate, and myocyte contractility. The abnormalities in expression and/or functions of eNOS lead to the development of cardiovascular diseases, both in animals and in humans. Although considerable research efforts have been dedicated to understanding the mechanisms of action of estradiol in regulating cardiac eNOS, more research is needed to fully understand the details of such mechanisms. This review focuses on recent findings from animal and human studies on the regulation of eNOS and HDL quality by estradiol in cardiovascular pathology.


Classification-related approach in the surgical treatment of thoracolumbar fractures.
Advanced diagnostic tools, classification systems and accordingly selected surgical approaches are essential requirements for the prevention of failure of surgical treatment of thoracolumbar fractures. The present study is designed to evaluate the contribution of classification to the choice of a surgical approach using the current fracture classification systems. We studied prospectively a group of 64 patients (22 females, 42 males) of an average age of 43 years, all operated on for thoracolumbar fractures during the year 2001. The AO-ASIF classification was used preoperatively with all imaging studies (X-ray, computed tomography (CT) and magnetic resonance imaging (MRI)). When the damage was detected only in the anterior column (A type), an isolated anterior stabilization (n = 22) was preferred. If the MRI study disclosed an injury in the posterior column, a posterior approach (n = 20) using the internal fixator was chosen. Injuries involving the posterior column (B or C type) were classified additionally according to the load-sharing classification (LSC). If LSC gave six or more points, treatment was completed with an anterior fusion. The combined postero-anterior procedure was carried out 22 times. The minimum followup period was 22 months. Neither implant failure and nor significant loss of correction were observed in patients treated with anterior or combined procedures. The average loss of correction (increase of kyphosis) in simple posterior stabilization was 3.1 degree. Complex fracture classification helps in the selection of the surgical approach and helps to decrease the chances of treatment failure.


[Post-traumatic stress after occupational accidents].
This study focuses on post-traumatic stress disorder in a follow up one to two years after the occupational accident. The aim was to estimate the prevalence of PTSD, changes in general health status and issues of compensation. The material was all serious accidents registered in the Danish National Register of Work Accidents during 1991. Seriousness was defined by type of injury, including all cases of amputations, bone fractures and extensive body lesions. Of 4745 possible, 3663 persons (77%) participated in a questionnaire study. The prevalence fulfilling the complete set of criteria of posttraumatic stress disorder as a chronic state was 2.8% (102 persons), of whom half had been given compensation. Among the most severe accidents the prevalence was 7.6%. In conclusion, in a large cohort of persons with moderate and severe occupational injuries this study demonstrated that post-traumatic stress disorder and lasting psychological distress should be a matter for concern in addition to the physical injury.


Comorbidity of anxiety disorders with anorexia and bulimia nervosa.
A large and well-characterized sample of individuals with anorexia nervosa and bulimia nervosa from the Price Foundation collaborative genetics study was used to determine the frequency of anxiety disorders and to understand how anxiety disorders are related to state of eating disorder illness and age at onset. Ninety-seven individuals with anorexia nervosa, 282 with bulimia nervosa, and 293 with anorexia nervosa and bulimia were given the Structured Clinical Interview for DSM-IV Axis I Disorders and standardized measures of anxiety, perfectionism, and obsessionality. Their ratings on these measures were compared with those of a nonclinical group of women in the community. The rates of most anxiety disorders were similar in all three subtypes of eating disorders. About two-thirds of the individuals with eating disorders had one or more lifetime anxiety disorder; the most common were obsessive-compulsive disorder (OCD) (N=277 [41%]) and social phobia (N=134 [20%]). A majority of the participants reported the onset of OCD, social phobia, specific phobia, and generalized anxiety disorder in childhood, before they developed an eating disorder. People with a history of an eating disorder who were not currently ill and never had a lifetime anxiety disorder diagnosis still tended to be anxious, perfectionistic, and harm avoidant. The presence of either an anxiety disorder or an eating disorder tended to exacerbate these symptoms. The prevalence of anxiety disorders in general and OCD in particular was much higher in people with anorexia nervosa and bulimia nervosa than in a nonclinical group of women in the community. Anxiety disorders commonly had their onset in childhood before the onset of an eating disorder, supporting the possibility they are a vulnerability factor for developing anorexia nervosa or bulimia nervosa.