Economics of dairy waste use as fertilizer in central Texas.
Dairy manure is an unavoidable natural, but negative, byproduct of milk production. Its nitrogen, phosphate, and potash contents represent a potential substitute for commercial fertilizers on field crops. In the absence of subsidies, manure transportation and land application costs limit its utilization as a substitute for chemical fertilizer. The results from a study of the economics of manure use in Central Texas suggest that, at the current costs for loading, hauling, and spreading, dairy manure cannot be economically transported from surplus to deficit areas within the study area. The estimated breakeven transport distance for manure application to four crops varied from 28 to 41 km; however, the distances between manure-surplus and manure-deficit counties in the study region varied from 40 to 90 km. An analysis of potential subsidies paid by the government or dairy farmers showed that the breakeven distance could increase by up to 30 km. A decrease in the assumed moisture content of the manure from 50% to 40% is shown to increase the breakeven distance by 10 km. The study suggests that dairy manure loading, transportation, and land application, with appropriate subsidies or reductions in moisture content, has the potential to be profitably substituted for chemical fertilizers.


[Providing athletes with trace elements during intensive exercise].
On the day of 30-km cross-country running, the content of iron, copper, and manganese in the diets of highly skilled adult athletes was found to be in the lower normal physiological range for those who do not go in for sports. During intensive exercise the intestinal and renal excretion of these substances was much greater than their dietary intake. The balance of all three substances was negative. Losses of iron and copper were not compensated for in the presence of their inadequate intake in the subsequent 3 days of rest following the race. The enrichment of diets with a complex of iron, copper, and manganese resulted in their retention in the athletes. As medical iron intake increased, there was a significant rise in the excretion of copper and manganese through the gastrointestinal tract.


Plasticity in the adrenocortical response of a free-living vertebrate: the role of pre- and post-natal developmental stress.
Optimal functioning of the hypothalamo-pituitary-adrenal (HPA) axis is paramount to maximizing fitness in vertebrates. Research in laboratory mammals has suggested that maternally-induced stress can cause significant variation in the responsiveness of an offspring's HPA axis involving both pre- and post-natal developmental mechanisms. However, very little is known regarding effects of maternal stress on the variability of offspring adrenocortical functioning in free-living vertebrates. Here we use an experimental approach that independently lowers the quality of both the pre- and post-natal developmental environment to examine programming and plasticity in the responsiveness of the HPA axis in fledglings of a free-living passerine, the European starling (Sturnus vulgaris). We found that mimicking a hormonal signal of poor maternal condition via an experimental pre-natal increase in yolk corticosterone decreased the subsequent responsiveness of the HPA axis in fledglings. Conversely, decreasing the quality of the post-natal developmental environment (by decreasing maternal provisioning capability via a maternal feather-clipping manipulation) increased subsequent responsiveness of the HPA axis in fledglings, apparently through direct effects on nestling body condition. The plasticity of these responses was sex-specific with smaller female offspring showing the largest increase in HPA reactivity. We suggest that pre-natal, corticosterone-induced, plasticity in the HPA axis may be a 'predictive adaptive response' (PAR): a form of adaptive developmental plasticity where the advantage of the induced phenotype is manifested in a future life-history stage. Further, we introduce a new term to define the condition-driven post-natal plasticity of the HPA axis to an unpredictable post-natal environment, namely a 'reactive adaptive response' (RAR). This study confirms that the quality of both the pre- and post-natal developmental environment can be a significant source of variation in the responsiveness of the HPA axis, and provides a frame-work for examining ecologically-relevant sources of stress-induced programming and plasticity in this endocrine system in a free-living vertebrate, respectively.


Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase.
The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 -/-, and Atf4 -/- mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 +/- mice. Here, we show that ATF4 controls a hepatic gene expression profile that overlaps with GCN2 but is not required for downregulation of mTORC1 during asparaginase. Ingenuity pathway analysis indicates GCN2 independently influences inflammation-mediated hepatic processes whereas ATF4 uniquely associates with cholesterol metabolism and endoplasmic reticulum (ER) stress. Livers from Atf4 -/- or Atf4 +/- mice displayed an amplification of the amino acid response and ER stress response transcriptional signatures. In contrast, reduction in hepatic mTORC1 signaling was retained in Atf4 -/- mice treated with asparaginase. GCN2 and ATF4 serve complementary roles in the hepatic response to asparaginase. GCN2 functions to limit inflammation and mTORC1 signaling whereas ATF4 serves to limit the amino acid response and prevent ER stress during amino acid depletion by asparaginase.


Outcomes and complications of 25-gauge transconjunctival sutureless vitrectomy for proliferative diabetic retinopathy.
To investigate the feasibility and efficacy of 25-gauge vitrectomy in the treatment of proliferative diabetic retinopathy (PDR). All patients underwent primary 25-gauge vitrectomy for simple vitreous hemorrhage (VH), fibrovascular proliferation (FVP), or tractional retinal detachment (TD), and were followed for more than 1 month. Final visual outcomes and intraoperative and postoperative complications were evaluated. 167 eyes (138 patients) were used in this study, 65 eyes (39%) with VH, 66 eyes (40%) with FVP, and 36 eyes (21%) with TD. Measured using the mean logarithm of the minimum angle of resolution (logMAR), visual acuity (VA) significantly improved (p < 0.0001). Intraoperative iatrogenic retinal breaks developed in 19 eyes (11%). Concerning postoperative complications, VH in 36 eyes (22%), retinal detachment in 2 eyes (1%), and neovascular glaucoma 12 eyes (7%) were observed. No endophthalmitis developed. Twenty-five-gauge vitrectomy can successfully treat PDR. Clinical outcomes and complications are comparable to those of 20-gauge vitrectomy.


Endoscopic Treatment of Jejunal Heterotopic Gastric Mucosa that Caused Recurrent Intussusception.
Heterotopic gastric mucosa (HGM) is a rare anomaly in the small bowel and may be the cause of intussusception when it gets a lead point in the jejunum. All cases of intussusception due to intestinal HGM have been treated with surgical resection. A 5-year-old girl presented with chief complaints of vomiting and abdominal pain for 2 weeks. A computed tomography scan of the abdomen showed intussusception at the proximal jejunal loops. Three air reductions and one saline reduction were attempted without success. She continued to be symptomatic, and endoscopic evaluation was performed. Enteroscopy revealed some variable-sized polypoid mucosal lesions with erosions on the proximal jejunum. Endoscopic mucosal resection was performed using a snare. The resected tissues histologically showed a hyperplastic polyp arising from the HGM. Her symptoms did not recur within 1 year after the treatment. Our case showed that enteroscopy could be useful for the diagnosis and management of jejunal intussusception caused by HGM.


Criminal offending before and after the onset of psychosis: examination of an offender typology.
Clinicians often consider whether or not offenders with psychosis have a history of offending pre-dating the onset of their illness. The typology of offenders based on age at first offence, developed in the field of criminology, has been recently extended to mentally disordered groups, but this ignores the potential role of illness onset. Using a large UK cohort of individuals with both psychosis and offending histories (n=331), we compared those with a history of offending pre-dating their illness (pre-morbid offenders) to those who commenced offending after becoming unwell (post-morbid offenders). We compared the demographic, clinical and offending pattern characteristics of the two groups. 198 (60%) had offended before the onset of psychosis. These pre-morbid offenders were more likely to be male, have a lower pre-morbid IQ and have had a history of neurological abnormality. Pre-morbid offenders also committed more crime overall, but this was due to an excess of acquisitive, drug and minor offending, rather than violent offending, which was comparable to the post-morbid offending group. Currently, standardised clinical risk assessment tools view offenders with mental illness as a homogenous group with respect to life-course patterns of offending in relation to illness. Taking account of an individual's pathway to offending may improve risk assessment and management.


Economic evaluation of alternative testing regimes and settings to detect undiagnosed HIV in Australia.
The study aimed to estimate the comparative costs per positive diagnosis of previously undetected HIV in three testing regimes: conventional; parallel and point of care (POC) testing. The regimes are analysed in six testing settings in Australia where infection is concentrated but with low prevalence. A cost model was developed to highlight the trade-offs between test and economic efficiency from a provider perspective. First, an estimate of the number of tests needed to find a true (previously undiagnosed) positive diagnosis was made. Second, estimates of the average cost per positive diagnosis in whole of population (WoP) and men who have sex with men (MSM) was made, then third, aggregated to the total cost for diagnosis of all undetected infections. Parallel testing is as effective as conventional testing, but more economically efficient. POC testing provide two significant advantages over conventional testing: they screen out negatives effectively at comparatively lower cost and, with confirmatory testing of reactive results, there is no loss in efficiency. The average and total costs per detection in WoP are prohibitive, except for Home Self Testing. The diagnosis in MSM is cost effective in all settings, but especially using Home Self Testing when the individual assumes the cost of testing. This study illustrates the trade-offs between economic and test efficiency and their interactions with population(s) prevalence. The efficient testing regimes and settings are presently under or not funded in Australia. Home Self Testing has the potential to dramatically increase testing rates at very little cost.


A protein relational database and protein family knowledge bases to facilitate structure-based design analyses.
The Protein Data Bank is the most comprehensive source of experimental macromolecular structures. It can, however, be difficult at times to locate relevant structures with the Protein Data Bank search interface. This is particularly true when searching for complexes containing specific interactions between protein and ligand atoms. Moreover, searching within a family of proteins can be tedious. For example, one cannot search for some conserved residue as residue numbers vary across structures. We describe herein three databases, Protein Relational Database, Kinase Knowledge Base, and Matrix Metalloproteinase Knowledge Base, containing protein structures from the Protein Data Bank. In Protein Relational Database, atom-atom distances between protein and ligand have been precalculated allowing for millisecond retrieval based on atom identity and distance constraints. Ring centroids, centroid-centroid and centroid-atom distances and angles have also been included permitting queries for pi-stacking interactions and other structural motifs involving rings. Other geometric features can be searched through the inclusion of residue pair and triplet distances. In Kinase Knowledge Base and Matrix Metalloproteinase Knowledge Base, the catalytic domains have been aligned into common residue numbering schemes. Thus, by searching across Protein Relational Database and Kinase Knowledge Base, one can easily retrieve structures wherein, for example, a ligand of interest is making contact with the gatekeeper residue.


PhoglyStruct: Prediction of phosphoglycerylated lysine residues using structural properties of amino acids.
The biological process known as post-translational modification (PTM) contributes to diversifying the proteome hence affecting many aspects of normal cell biology and pathogenesis. There have been many recently reported PTMs, but lysine phosphoglycerylation has emerged as the most recent subject of interest. Despite a large number of proteins being sequenced, the experimental method for detection of phosphoglycerylated residues remains an expensive, time-consuming and inefficient endeavor in the post-genomic era. Instead, the computational methods are being proposed for accurately predicting phosphoglycerylated lysines. Though a number of predictors are available, performance in detecting phosphoglycerylated lysine residues is still limited. In this paper, we propose a new predictor called PhoglyStruct that utilizes structural information of amino acids alongside a multilayer perceptron classifier for predicting phosphoglycerylated and non-phosphoglycerylated lysine residues. For the experiment, we located phosphoglycerylated and non-phosphoglycerylated lysines in our employed benchmark. We then derived and integrated properties such as accessible surface area, backbone torsion angles, and local structure conformations. PhoglyStruct showed significant improvement in the ability to detect phosphoglycerylated residues from non-phosphoglycerylated ones when compared to previous predictors. The sensitivity, specificity, accuracy, Mathews correlation coefficient and AUC were 0.8542, 0.7597, 0.7834, 0.5468 and 0.8077, respectively. The data and Matlab/Octave software packages are available at https://github.com/abelavit/PhoglyStruct .


Surgical Implications for Diagnosis and Treatment of Intestinal Aspergillosis in Pediatric Patients with ALL.
The incidence of invasive aspergillosis (IA) in children with hematooncological malignancies is increasing as a result of intensive treatment, immunosuppression, and extended use of broad-spectrum antibiotics. Infection of the GI tract by Aspergillus spp. is a rare and fatal complication, which often requires surgical diagnostic and therapeutic exploration. The aim of this study was to determine the characteristics of symptomatic intestinal aspergillosis, diagnosis, treatment, and outcome of pediatric patients with an underlying hemato-oncologic disease. We analyzed 2,307 German patients with acute lymphoblastic leukemia (ALL) from age 1 to 17 years registered in the AIEOP-BFM ALL 2000 study from 2000 to 2006. All reported adverse events were assessed for symptoms of IA and retrospectively reviewed for any sign or proof of intestinal involvement of IA. In this cohort, IA was reported in 30 of 2,307 patients while intestinal involvement was documented in five patients. Four of these patients had intestinal symptoms and three patients underwent explorative laparotomy. Among clinical cases with IA, gastrointestinal manifestation of IA mostly occurred in adolescent patients (10-16 years). Symptoms varied from abdominal tenderness and pain to constipation. Intestinal aspergillosis was proven by microbiological and histopathological examination and fungal infection was observed macroscopically in the jejunal lumen during surgery. Despite the extended surgery and antifungal therapy, outcome of disseminated IA with intestinal involvement remains poor. Surgeons should be aware of surgical complications of intestinal aspergillosis in children with hematooncological diseases requiring exploration and resection. IA is a rare event and still difficult to diagnose due to unspecific abdominal symptoms. Thus, biopsy sampling is of utmost importance to ensure diagnosis, and resection of necrotic or perforated tissue should be attempted early.


Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes.
Diabetic women are more susceptible to develop lower urinary tract symptoms (LUTS), especially overactive bladder (OAB). However, data regarding the effect of components of metabolic syndrome (MS) on this association are conflicting. The objective of the study was to examine the potential role of MS in the development of LUTS in diabetic women. The study was a prevalence study conducted between 2005 and 2007. The study was conducted in a university hospital. A total of 518 women with type 2 diabetes aged 50-75 yr were included. They were subgrouped as MS (47.5%) and non-MS (52.5%) groups according to whether they fulfilled the criteria of MS. We used American Urological Association Symptom Index (AUA-SI) to evaluate LUTS and Indevus Urgency Severity Scale to evaluate OAB, respectively. Women in the MS group had significantly higher storage and total AUA-SI scores as well as a higher prevalence of LUTS and OAB. Most intriguingly, the number of MS components was strongly associated with the LUTS severity because the AUA-SI scores increased in parallel to the number of components were present. Similar results were found between MS and OAB. Multivariate analysis revealed that peripheral neuropathy, but not MS, significantly predicted LUTS in diabetic women after age adjustment. However, MS remained significantly predictive for LUTS and OAB after additional adjustment for neuropathy. Our results suggest that MS may especially influence LUTS and OAB in diabetic women, probably by compounding the effect of peripheral neuropathy.


Localization of three DNA segments encompassing tRNA genes to human chromosomes 1, 5, and 16: proposed mechanism and significance of tRNA gene dispersion.
The chromosomal locations of three cloned human DNA fragments encompassing tRNA genes have been determined by Southern analysis of human-rodent somatic cell hybrid DNAs with subfragments from these cloned genes and flanking sequences used as hybridization probes. These three DNA segments have been assigned to human chromosomes 1, 5, and 16, and homologous sequences are probably located on chromosome 14 and a separate locus on chromosome 1. These studies, combined with previous results, indicate that tRNA genes and pseudogenes are dispersed on at least seven different human chromosomes and suggest that these sequences will probably be found on most, if not all, human chromosomes. Short (8-12 nucleotide) direct terminal repeats flank many of the dispersed tRNA genes. The presence of these flanking repeats, combined with the dispersion of tRNA genes throughout the human genome, suggests that many of these genes may have arisen by an RNA-mediated retroposition mechanism. The possible functional significance of this gene dispersion is considered.


Usage and perceived effectiveness of fatigue countermeasures for professional and nonprofessional drivers.
Drivers adopt various strategies in order to cope with fatigue and falling asleep at the wheel. These strategies include a wide range of activities that may invigorate the body and/or the mind. To compare usage patterns and to evaluate the perceived effectiveness of different coping behaviors adopted by professional and nonprofessional drivers in order to maintain alertness. The study was conducted using a large-scale survey, filled by 100 professional and 90 nonprofessional drivers. Listening to the radio and opening the window were the most frequently used and also perceived as highly effective coping behaviors by both groups of drivers. Talking on a cellular phone or with a passenger were more frequently used by nonprofessional drivers whereas, planning rest stops ahead, stopping for a short nap and drinking coffee were more frequently used by professional drivers. These methods were also perceived as more effective by professional than by the nonprofessional drivers and their usage frequency highly correlated with their perceived effectiveness. Nonprofessional drivers counteract fatigue only at the tactical/maneuvering level of the drive. Hence, they tend to adopt methods that help them pass the time and reduce their feeling of boredom but do not require advance preparations or adjustments in the driving. In contrast, professional drivers counteract fatigue also at the strategic/planning level of driving, and use a much larger repertoire of coping-behaviors. Fatigue countermeasures should include all levels of the driving task hierarchy, and experience-based countermeasures used by professional drivers should be considered for experimental validation.


Gene expression ontogeny of spermatogenesis in the marmoset uncovers primate characteristics during testicular development.
Mammalian spermatogenesis has been investigated extensively in rodents and a strictly controlled developmental process has been defined at cellular and molecular levels. In comparison, primate spermatogenesis has been far less well characterized. However, important differences between primate and rodent spermatogenesis are emerging so it is not always accurate to extrapolate findings in rodents to primate systems. Here, we performed an extensive immunofluorescence study of spermatogenesis in neonatal, juvenile, and adult testes in the common marmoset (Callithrix jacchus) to determine primate-specific patterns of gene expression that underpin primate germ cell development. Initially we characterized adult spermatogonia into two main classes; mitotically active C-KIT(+)Ki67(+) cells and mitotically quiescent SALL4(+)PLZF(+)LIN28(+)DPPA4(+) cells. We then explored the expression of a set of markers, including PIWIL1/MARWI, VASA, DAZL, CLGN, RanBPM, SYCP1 and HAPRIN, during germ cell differentiation from early spermatocytes through round and elongating spermatids, and a clear program of gene expression changes was determined as development proceeded. We then examined the juvenile marmoset testis. Markers of gonocytes demonstrated two populations; one that migrates to the basal membrane where they form the SALL4(+) or C-KIT(+) spermatogonia, and another that remains in the lumen of the seminiferous tubule. This later population, historically identified as pre-spermatogonia, expressed meiotic and apoptotic markers and were eliminated because they appear to have failed to correctly migrate. Our findings provide the first platform of gene expression dynamics in adult and developing germ cells of the common marmoset. Although we have characterized a limited number of genes, these results will facilitate primate spermatogenesis research and understanding of human reproduction.


The partnership with affiliates: our stories.
The National Kidney Foundation (NKF) began as a grass roots federation of affiliates. In the 1950s, there were five original affiliates: Illinois, Michigan New York/New Jersey, Ohio, and Wisconsin. Twenty-two affiliates developed in the 1960s and 12 more in the 1970s; the 1980s and 1990s brought changing affiliate configurations. After 50 years of progress, there are 52 affiliates in the NKF. As the national organization has grown, evolved, and prospered, each affiliate has also grown in unique and individual directions. Each affiliate has its own important history; unfortunately, space limitations preclude recounting all of them. Instead, we offer a limited collection of diverse anecdotes, stories, and vignettes from our affiliates. We hope that these reflect the richness and diversity of the ongoing histories of the affiliates of the NKF.


Cervical Paraspinal Muscle Fatty Degeneration Is Not Associated with Muscle Cross-sectional Area: Qualitative Assessment Is Preferable for Cervical Sarcopenia.
Sarcopenia, defined as decreased skeletal mass, is an independent marker of frailty that is not accounted for by other risk-stratification methods. Recent studies have demonstrated a clear association between paraspinal sarcopenia and worse patient-reported outcomes and complications after spine surgery. Currently, sarcopenia is characterized according to either a quantitative assessment of the paraspinal cross-sectional area or a qualitative analysis of paraspinal fatty infiltration on MRI. No studies have investigated whether the cervical paraspinal cross-sectional area correlates with fatty infiltration of the cervical paraspinal muscles on advanced imaging. Do patients undergoing anterior cervical discectomy and fusion (ACDF) with increasing paraspinal fatty degeneration on advanced imaging also demonstrate decreased cervical paraspinal cross-sectional area? Between 2011 and 2017, 98 patients were prospectively enrolled in a database of patients undergoing one- to three-level ACDF for degenerative conditions at a single institution. To be eligible for this prospective study, patients were required to undergo an MRI before surgery, be older than 18 years, and have no previous history of cervical spine surgery. Two independent reviewers, both surgeons not involved in the patients' care and who were blinded to the clinical outcomes, retrospectively assessed the paraspinal cross-sectional area and Goutallier classification of the right-sided paraspinal muscle complex. We then compared the patients' Goutallier grades with their paraspinal cross-sectional area measurements. We identified 98 patients for inclusion. Using the Fuchs modification of the Goutallier classification, we classified the fatty degeneration of 41 patients as normal (Goutallier Grades 0 to 1), that of 47 patients as moderate (Grade 2), and that of 10 patients as severe (Grades 3 to 4). We used ANOVA to compare all means between groups. There was no difference in the mean paraspinal cross-sectional area of the obliquus capitus inferior (normal 295 ± 81 mm2; moderate 317 ± 104 mm2; severe 300 ± 79 mm2; p = 0.51), multifidus (normal 146 ± 59 mm2; moderate 170 ± 70 mm2; severe 192 ± 107 mm2; p = 0.11), or sternocleidomastoid (normal 483 ± 150 mm2; moderate 468 ± 149 mm2; severe 458 ± 183 mm2; p = 0.85) among patients with mild, moderate, and severe fatty infiltration based on Goutallier grading. There was a slightly greater longus colli cross-sectional area in the moderate and severe fatty infiltration groups (74 ± 22 mm2 and 66 ± 18 mm2, respectively) than in the normal group (63 ± 15 mm2; p = 0.03). Because our study demonstrates minimal association between paraspinal cross-sectional area and fatty infiltration of the cervical paraspinals, we recommend that physicians use the proven qualitative assessment of paraspinal fatty infiltration during preoperative evaluation of patients who are candidates for ACDF. Future studies investigating the relationship between cervical paraspinal cross-sectional area and patient-reported outcomes after ACDF are necessary to lend greater strength to this recommendation. Level III, diagnostic study.


Physical performance and cardiovascular and metabolic adaptation of elite female wheelchair basketball players in wheelchair ergometry and in competition.
Spinal cord injury leads to a pronounced reduction of cardiovascular, pulmonary, and metabolic ability. Physical activity, up to and including high-performance sports, has obtained importance in the course of rehabilitation and the postclinical phase. Thirteen elite female wheelchair basketball players from the German National Basketball Team and 10 female sedentary spinal cord-injured persons were examined in the study. Heart volume was measured by an echocardiography. All subjects underwent a graded exercise test on a wheelchair ergometer. Additionally, heart rate, lactate, and player points were measured during a competitive basketball game in wheelchair basketball players. Cardiac dimensions were larger for spinal cord-injured wheelchair basketball players (620.3 ml; 9.6 ml x kg(-1)) in comparison with spinal cord-injured persons (477.4 ml; 8.2 ml x kg(-1)) but did not exceed the heart volume of untrained nonhandicapped persons. In contrast, athletes with amputations or those having had poliomyelitis reached training-induced cardiac hypertrophy in relation to body mass (713.7 ml; 13.2 ml x kg(-1)), as observed in nonhandicapped athletes. During graded wheelchair ergometry, wheelchair basketball players showed a higher maximal work rate (59.9 v 45.5 W), maximal oxygen consumption (33.7 v 18.3 ml x min(-1) x kg(-1)), and maximal lactate (9.1 v 5.47 mmol x l(-1)) without a difference in maximal heart rate and workload at AT4 than did spinal cord-injured persons. The average heart rate during the wheelchair basketball game was 151 x min(-1), and the lactate concentration was 1.92 mmol x l(-1). Female athletes with a less severe handicap and higher maximal oxygen consumption during the graded exercise test reached a higher game level in the evaluation. During the competitive basketball game, high cardiovascular stress was observed, indicating a fast aerobic metabolism; the anaerobic lactic acid capacity played a subordinate role. Wheelchair basketball is an effective and suitable sport to enhance physical performance and to induce positive physiological adaptations.


Denial and concealment of eating disorders: a retrospective survey.
To get an idea of how (ex-)patients deal with the recognition of an emergent eating disorder. A retrospective survey was carried out via the websites of two organizations for (ex-)patients with an eating disorder. The respondents (N = 401) reported a variety of attempts to conceal their eating disorder: excuses to avoid eating together, methods to give the false impression of having eaten, avoidance of being weighed and falsifying weight. Often these methods were described as a deliberate strategy. Information about possible health risks had little or no impact on most respondents, who were familiar with the notion of eating disorder but did not apply it to themselves. Many believed they would have recognized their eating disorder earlier if they had met a clinician who was familiar with this disorder. Denial of illness together with concealment often reflects a deliberate refusal of self-disclosure within a specific interpersonal context.


Induction of an adaptive response in Drosophila imaginal disc cells exposed in vivo to low doses of alkylating agents.
The adaptive response of Drosophila larvae to three alkylating agents (ethyl methanesulfonate, methyl methanesulfonate and N-nitroso-N-ethylurea) has been studied in the wing spot test. The experimental procedure included a 24 h pretreatment of 2-day-old larvae with two different adaptive doses followed by a challenge dose applied until the end of development. The genotoxic effects were analysed in trans-heterozygous larvae for the third chromosome recessive markers multiple wing hairs (mwh) and flare (flr(3)). Genetic changes induced in somatic cells of the wing imaginal discs led to loss of heterozygosity, expressed as mutant clones of the genetic markers used. From our results it appears that the adaptive doses clearly reduce the frequency of mutant clones induced by the challenge dose. As far as we know, this is the first time that the existence of an adaptive response to alkylating agents after Drosophila larval treatment has been reported using the wing spot assay.


Genetic regulation of the RUNX transcription factor family has antitumor effects.
Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members. Switching off the RUNX cluster using alkylating agent-conjugated pyrrole-imidazole (PI) polyamides, which were designed to specifically bind to consensus RUNX-binding sequences, was highly effective against AML cells and against several poor-prognosis solid tumors in a xenograft mouse model of AML without notable adverse events. Taken together, these results identify a crucial role for the RUNX cluster in the maintenance and progression of cancer cells and suggest that modulation of the RUNX cluster using the PI polyamide gene-switch technology is a potential strategy to control malignancies.


Bipolar obsessive-compulsive disorder and personality disorders.
Relatively few systematic data exist on the clinical impact of bipolar comorbidity in obsessive-compulsive disorder (OCD) and no studies have investigated the influence of such a comorbidity on the prevalence and pattern of Axis II comorbidity. The aim of the present study was to explore the comorbidity of personality disorders in a group of patients with OCD and comorbid bipolar disorder (BD). The sample consisted of 204 subjects with a principal diagnosis of OCD (DSM-IV) and a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score>or=16 recruited from all patients consecutively referred to the Anxiety and Mood Disorders Unit, Department of Neuroscience, University of Turin over a period of 5 years (January 1998-December 2002). Diagnostic evaluation and Axis I comorbidities were collected by means of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Personality status was assessed by using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). Socio-demographic and clinical features (including Axis II comorbidities) were compared between OCD patients with and without a lifetime comorbidity of BD. A total of 21 patients with OCD (10.3%) met DSM-IV criteria for a lifetime BD diagnosis: 4 (2.0%) with BD type I and 17 (8.3%) with BD type II. Those without a BD diagnosis showed significantly higher rates of male gender, sexual and hoarding obsessions, repeating compulsions and lifetime comorbid substance use disorders, when compared with patients with BD/OCD. With regard to personality disorders, those with BD/OCD showed higher prevalence rates of Cluster A (42.9% versus 21.3%; p=0.027) and Cluster B (57.1% versus 29.0%; p=0.009) personality disorders. Narcissistic and antisocial personality disorders were more frequent in BD/OCD. Our results point towards clinically relevant effects of comorbid BD on the personality profiles of OCD patients, with higher rates of narcissistic and antisocial personality disorders in BD/OCD patients.


Direct evidence of intracrine angiotensin II signaling in neurons.
The existence of a local renin-angiotensin system (RAS) in neurons was first postulated 40 years ago. Further studies indicated intraneuronal generation of ANG II. However, the function and signaling mechanisms of intraneuronal ANG II remained elusive. Since ANG II type 1 receptor (AT1R) is the major type of receptor mediating the effects of ANG II, we used intracellular microinjection and concurrent Ca(2+) and voltage imaging to examine the functionality of intracellular AT1R in neurons. We show that intracellular administration of ANG II produces a dose-dependent elevation of cytosolic Ca(2+) concentration ([Ca(2+)]i) in hypothalamic neurons that is sensitive to AT1R antagonism. Endolysosomal, but not Golgi apparatus, disruption prevents the effect of microinjected ANG II on [Ca(2+)]i. Additionally, the ANG II-induced Ca(2+) response is dependent on microautophagy and sensitive to inhibition of PLC or antagonism of inositol 1,4,5-trisphosphate receptors. Furthermore, intracellular application of ANG II produces AT1R-mediated depolarization of hypothalamic neurons, which is dependent on [Ca(2+)]i increase and on cation influx via transient receptor potential canonical channels. In summary, we provide evidence that intracellular ANG II activates endolysosomal AT1Rs in hypothalamic neurons. Our results point to the functionality of a novel intraneuronal angiotensinergic pathway, extending the current understanding of intracrine ANG II signaling.


Auditory brainstem implantation.
The use of cochlear implants for selected individuals with bilateral severe to profound sensorineural hearing loss who derive limited benefit from conventional hearing aids is well established. There are situations where cochlear implantation is contraindicated. Auditory brainstem implantation (ABI) is the only solution to restore hearing when the cochlear nerve is disrupted together with pathologies where the cochlea does not provide a suitable location for cochlear implant. Labyrinthine and cochlear aplasia and cochlear nerve aplasia constitute the congenital indications for ABI. In the present review article history and development of ABI, indications, side selection criteria, surgery and audiological outcome are presented.


Factors controlling the regional distribution of vanadium in groundwater.
Although the ingestion of vanadium (V) in drinking water may have possible adverse health effects, there have been relatively few studies of V in groundwater. Given the importance of groundwater as a source of drinking water in many areas of the world, this study examines the potential sources and geochemical processes that control the distribution of V in groundwater on a regional scale. Potential sources of V to groundwater include dissolution of V rich rocks, and waste streams from industrial processes. Geochemical processes such as adsorption/desorption, precipitation/dissolution, and chemical transformations control V concentrations in groundwater. Based on thermodynamic data and laboratory studies, V concentrations are expected to be highest in samples collected from oxic and alkaline groundwater. However, the extent to which thermodynamic data and laboratory results apply to the actual distribution of V in groundwater is not well understood. More than 8400 groundwater samples collected in California were used in this study. Of these samples, high (> or =50 microg/L) and moderate (25 to 49 microg/L) V concentrations were most frequently detected in regions where both source rock and favorable geochemical conditions occurred. The distribution of V concentrations in groundwater samples suggests that significant sources of V are mafic and andesitic rock. Anthropogenic activities do not appear to be a significant contributor of V to groundwater in this study. High V concentrations in groundwater samples analyzed in this study were almost always associated with oxic and alkaline groundwater conditions, which is consistent with predictions based on thermodynamic data.


Alpha-fetoprotein to transaminase ratio is related to higher diagnostic efficacy for hepatocellular carcinoma.
Alpha-fetoprotein (AFP), as the most widely used biomarker of hepatocellular carcinoma (HCC), was correlated with ongoing liver damage. The aim of this study was to evaluate the ability of inflammatory correction-based AFP to identify HCC from other liver diseases.From March 2012 to March 2017, among 926 participants, a total of 501 patients whose transaminases were higher than the upper limit of normal range, including 166 treatment-naïve HCC patients were enrolled in our retrospective study. The liver function, white blood cell (WBC) count and serum AFP level of all patients were collected at the initial stage of admission. The area under the receiver-operating curve (AUROC) of AFP, AFP/(Aspartate aminotransferase*Alanine aminotransferase) [AFP/(AST*ALT)] and AFP/WBC were compared between the HCC group and the control groups for the quantifying diagnostic efficacy.AUROCs of our novel index AFP/(AST*ALT) were up to 0.853 (95% confidence interval, CI 0.818-0.887, P < .001) and 0.825 (95% CI 0.782-0.868, P < .001), respectively, when differentiating HCC from non-HCC patients and from cirrhosis patients, which was superior to AFP and AFP/WBC. Diagnostic performance of AFP/(AST*ALT) could be verified in hepatitis B virus (HBV)- or hepatitis C virus (HCV)-associated HCC patients as well. What's more, AFP/(AST*ALT) had a significant positive and moderate correlation with tumor diameter and presence of cancerous emboli or not (Spearman correlation coefficients were 0.323 and 0.305, respectively; both P < .001). For predicting HCC, the optimal cut-off value of AFP/(AST*ALT) is 1.603, and the sensitivity and specificity were 82.8% and 72.7%, respectively, which were significantly higher than the AFP and AFP/WBC.The serum AFP levels based on correction of liver inflammation can effectively improve the diagnostic performance of HCC, providing a new indicator that is simple, economical and pervasive for clinic.


Next generation of preventive interventions.
With increasing numbers of efficacious prevention programs, the field needs strategies to disseminate the interventions broadly. The authors examined the life course of prevention programs, identified barriers to dissemination, and outlined an alternative dissemination model. Private enterprise models of product development can be viable strategies for increasing the dissemination of the intervention to the general public. Market principles suggest that the next generation of interventions would be facilitated if interventions are initiated by teams committed to a specific problem and investigators receive training in management; if the acceptability of the program's design features to consumers, providers, and funding agencies is established prior to the development and evaluation of the program; if data from national marketing surveys are used to tailor intervention designs and delivery formats for different subgroups; if essential ingredients of the intervention are identified to facilitate adaptation of the program; if the program is implemented with a goal to maintain change over extended periods of time; if the implementation plan includes program evolution over time, rather than replication with fidelity; and if interventions are branded and certified by a credible agency. Private enterprise models may be useful; however, investigators are likely to be resistant given a priori biases, potential ethical conflicts of interest, and the challenges presented by new technologies (e.g., the Internet and Human Genome Project).


Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression.
Bone morphogenetic protein-2 (BMP-2) promotes the differentiation of non-osteogenic mesenchymal cells to osteogenic cells. In this study, we isolated human adipose-derived stem cells (hASCs) and investigated the effects of recombinant human BMP-2 (rhBMP-2) and extracellular Ca2+ concentration ([Ca2+]out) on the osteogenic differentiation of hASCs. rhBMP-2 promoted calcium deposition in hASCs and stimulated the mRNA expressions of six proteins known to be involved in the osteogenic differentiation of hASCs: Runx2, osterix, alkaline phosphatase, osteonectin, bone sialoprotein and osteocalcin. Elevation of [Ca2+]out enhanced the level of alkaline phosphatase enzyme, increased the mRNA expressions of Runx2 and osteocalcin and induced the expressions of BMP-2 mRNA and protein in hASCs. Elevation of [Ca2+]out transiently increased the intracellular Ca2+ concentration ([Ca2+]in) due to activation of the calcium-sensing receptor (CaSR). The Ca2+-induced expressions of BMP-2 mRNA and protein were inhibited by the calmodulin antagonist, W-7. Furthermore, elevation of [Ca2+]out decreased the cytoplasmic level of phosphorylated nuclear factor of activated T-cell-2 (NFAT-2) and increased the nuclear level of dephosphorylated NFAT2. Taken together, these results suggest that rhBMP-2 promotes the osteogenic differentiation of hASCs. Furthermore, an increase in [Ca2+]out enhances the expression of BMP-2 via activation of the CaSR, elevation of [Ca2+]in and stimulation of Ca2+/calmodulin-dependent NFAT-signaling pathways.


New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis.
New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or 'reverse' the anticoagulant effects for urgent invasive procedures.


Emphysema, airflow limitation, and early age-related macular degeneration.
To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV(1)) and FEV(1) to forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the association of lung function and structure with AMD, controlling for age, sex, and other factors. The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV(1) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P = .25), FEV(1):FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P = .43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P = .26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P = .17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those who ever smoked (OR, 1.28; 95% CI, 1.02-1.60; P = .03). Associations were not modified by race/ethnicity. Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort.


Late angiographic follow-up after successful coronary arterial thrombolysis and angioplasty during acute myocardial infarction.
Emergency percutaneous transluminal coronary angioplasty (PTCA) is accepted as an important reperfusion intervention for acute myocardial infarction (AMI). Although its primary success rate is well documented, the frequency of restenosis after this procedure is unclear. The frequency of restenosis was determined in patients undergoing emergency PTCA at least 6 months after PTCA was performed during AMI. Of 66 consecutive patients undergoing emergency PTCA, 25 had a second, elective catheterization at an average of 22 months after AMI and 6 underwent repeat catheterization because of recurrent chest pain. Restenosis of the PTCA site was found in 10 of the 31 patients (32%) restudied. Also, 14 (45%) of these 31 patients showed progression of narrowing in the non-infarct-related coronary arteries. In summary, patients in whom AMI is treated by PTCA are at risk for restenosis and for progressive narrowing of the non-infarct artery.


Intergenerational effects of prenatal ethanol on glucose tolerance and insulin response.
Consequences of prenatal exposure to ethanol (E) include morphological, physiological, and cognitive deficits and are collectively classified as fetal alcohol spectrum disorders. Adult prenatal E exposed offspring show insulin resistance, and given that in utero hyperglycemic environment can cause metabolic disorders in subsequent generations; we investigated the effects of grandmaternal E on functional glucose and insulin responses of the second generation. Sprague-Dawley (S) rat dams, mated with S males, received E-containing liquid diet and two different control diets between gestational days 8 and 20. Additionally, because prenatal E-induced behavioral deficits can be reversed by simultaneous thyroxine (T4) treatment, another group of dams received 0.3 mg/l T4 in their E diet. Their first-generation (F1) offspring were mated with control Brown Norway (B) males or females to produce SB and BS F2 progeny. Dams consuming E during pregnancy were hyperglycemic, and their F1 offspring showed insulin resistance in the glucose tolerance test (GTT). However, F2 responses to GTT varied based on the sex of prenatal E-exposed parent. BS F2 females, and both male and female SB F2 progeny, displayed hypoglycemic and hyperinsulinemic GTT response patterns. Although administering T4 to E dams normalized thyroid function of the F1 generation, it did not reverse their prenatal E-induced metabolic dysfunction. In contrast, administration of T4 to the alcohol-consuming grandmother reversed or alleviated the aberrant GTT responses of the F2 progeny. Prenatal E-induced dysregulation of glucose metabolism can affect the next generation, possibly via ethanol effects on the germline of the F1 fetus.


Integrative analysis of cancer imaging readouts by networks.
Cancer is a multifactorial and heterogeneous disease. The corresponding complexity appears at multiple levels: from the molecular and the cellular constitution to the macroscopic phenotype, and at the diagnostic and therapeutic management stages. The overall complexity can be approximated to a certain extent, e.g. characterized by a set of quantitative phenotypic observables recorded in time-space resolved dimensions by using multimodal imaging approaches. The transition from measures to data can be made effective through various computational inference methods, including networks, which are inherently capable of mapping variables and data to node- and/or edge-valued topological properties, dynamic modularity configurations, and functional motifs. We illustrate how networks can integrate imaging data to explain cancer complexity, and assess potential pre-clinical and clinical impact.


Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.
AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function. The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82). FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.


The Globodera pallida Effector GpPDI1 Is a Functional Thioredoxin and Triggers Defense-Related Cell Death Independent of Its Enzymatic Activity.
The plant-parasitic nematode Globodera pallida is an obligate biotroph that only reproduces on select species in the Solanum family. The establishment of the feeding site, the syncytium, involves secretion of effectors into the plant cell to combat the plant defense response and facilitate transformation of root cells into the syncytium. Despite the important predicted roles of effectors in the plant-pathogen interactions, the functionality of G. pallida effectors is largely unknown. In this study, we identified and characterized a G. pallida effector protein disulfide isomerase (GpPDI1). GpPDI1 contains two thioredoxin domains that function together to reduce disulfide bonds, as manifested by the nullification of enzymatic activity when either domain is absent. The transcript of GpPDI1 is localized in the dorsal gland of the nematode during the J2 stage. In addition, GpPDI1 can trigger defense-related cell death in Nicotiana benthamiana and tomato (Solanum lycopersicum) leaf tissue and localizes in the plant host cell's cytoplasm and nucleus when transiently expressed in plant cells. Significantly, the ability of elicitation of cell death is not dependent on the enzymatic activity of GpPDI1 or correlated with the subcellular distribution of GpPDI1, suggesting that a nondisulfide reducing function or structural feature of GpPDI1 is responsible for the recognition by the host immune system to elicit cell death.


The endothelium in health and disease--a target for therapeutic intervention.
In this review we discuss the contribution of NO, prostacyclin and endothelium-derived relaxing factor--endothelium-derived hyperpolarizing factor, or EDHF, to vascular function. We also explore the hypotheses (1): that tissues can store NO as nitrosothiols (RSNOs) and (2) that such RSNO stores can be modulated by physiological and pathophysiological processes. Notably in the microcirculation, EDHF appears to play an important role in the regulation of vascular tone. Leading candidates for EDHF include extracellular potassium (K+), an epoxygenase product, hydrogen peroxide and/or a contribution from myoendothelial gap junctions. Data from our laboratory indicate that in mouse vessels, different endothelium-dependent vasodilators, such as acetylcholine and protease-activated receptor (PAR) agonists, release different endothelium-derived relaxing factors. The combination of two K-channel toxins, apamin and charybdotoxin, inhibits EDHF activity in most protocols. Endothelial dysfunction is considered as the major risk factor and a very early indicator of cardiovascular disease including the cardiovascular complications of type I & types II diabetes. Impaired endothelium-dependent vasodilatation results primarily from a decreased synthesis of endothelium-derived nitric oxide (NO) and/or an increase in the production of reactive oxygen species such as superoxide. We have shown that the administration of tetrahydrobiopterin, an important co-factor for nitric oxide synthase (NOS) partially restores endothelial function (1) in leptin-deficient mice (db/db) with spontaneous type II diabetes, as well as (2) in human vascular tissue harvested for coronary artery bypass grafting (CABG). These data suggest that a deficiency in the availability of tetrahydrobiopterin plays an important role in vascular dysfunction associated with Type II diabetes. In addition, changes in the contribution of EDHF occur in vascular tissue from the db/db mice suggesting a compensatory increase in EDHF production; whether this alteration in EDHF production is physiological or pathophysiological remains controversial.


Fabrication of Nanostructured Omniphobic and Superomniphobic Surfaces with Inexpensive CO2 Laser Engraver.
Superomniphobic surfaces (i.e., surfaces that are extremely repellent to both high surface tension liquids like water and low surface tension liquid like oils) can be fabricated through a combination of surface chemistry that imparts low solid surface energy with a re-entrant surface texture. Recently, surface texturing with lasers has received significant attention because laser texturing is scalable, solvent-free, and can produce a monolithic texture on virtually any material. In this work, we fabricated nanostructured omniphobic and superomniphobic surfaces with a variety of materials using a simple, inexpensive and commercially available CO2 laser engraver. Further, we demonstrated that the nanostructured omniphobic and superomniphobic surfaces fabricated using our laser texturing technique can be used to design patterned surfaces, surfaces with discrete domains of the desired wettability, and on-surface microfluidic devices.


Upper gastrointestinal hemorrhage secondary to erosion of a biliary Wallstent in a woman with pancreatic cancer.
A 77-year-old patient with unresectable pancreatic adenocarcinoma sustained a life-threatening, upper gastrointestinal hemorrhage 1 month after placement of a biliary Wallstent. Radiographic and endoscopic studies revealed a choledocho-arterio-enteric fistula caused by erosion of the stent through the posterior duodenal wall. The patient was treated successfully with arterial embolization. This represents an unusual case of arterial bleeding with choledocho-arterio-enteric fistulization into the duodenum subsequent to biliary stent erosion.


Incidence and mortality of infective endocarditis in the last decade: a single center study.
Infective endocarditis (IE) is a significant disease characterized by high mortality and complications. The aim of this study was to evaluate the incidence/100 000 inhabitants and the in-hospital mortality/100 000 inhabitants of IE during the last 10 years in the province of Ravenna. We reviewed the public hospitals discharge database from January 2010 to December 2020 using the international classification of disease codification (ICD-9) for IE. We used the Italian national statistical institute (ISTAT) archive to estimate the number of Ravenna inhabitants/year. In 10 years, we identified a total of 407 patients with diagnosis of IE.The incidence of IE increased significantly from 6.29 cases/100 000 inhabitants in 2010 to 19.58 cases/100 000 inhabitants in 2020 ( P < 0.001). Also, the in-hospital mortality from IE increased over the same number of years, from 1.8 deaths/100 000 inhabitants in 2010 to 4.4 deaths/100 000 inhabitants in 2020 ( P < 0.001). The mortality rate (%) of IE over the years did not increase ( P = 0.565). Also, over the years there was no difference in the site of infection ( P = 0.372), irrespective of the valve localization or type, native valve ( P = 0.347) or prosthetic valve ( P = 0.145). On logistic regression analysis, age was the only predictor of in-hospital mortality (odds ratio 1.045, 95% confidence interval: 1.015; 1.075, P = 0.003). Ravenna-based data on IE showed increased disease incidence but unchanged mortality rate over 10 years of follow-up. Age remains the sole predictor of population-based mortality, irrespective of the nature of the valve, native or substitute, and the organism detected on microbiology.


The distribution of species diversity across a flora's component lineages: dating the Cape's 'relicts'.
The Cape Floristic Region is exceptionally species-rich both for its area and latitude, and this diversity is highly unevenly distributed among genera. The modern flora is hypothesized to result largely from recent (post-Oligocene) speciation, and it has long been speculated that particular species-poor lineages pre-date this burst of speciation. Here, we employ molecular phylogenetic data in combination with fossil calibrations to estimate the minimum duration of Cape occupation by 14 unrelated putative relicts. Estimates vary widely between lineages (7-101 Myr ago), and when compared with the estimated timing of onset of the modern flora's radiation, it is clear that many, but possibly not all, of these lineages pre-date its establishment. Statistical comparisons of diversities with lineage age show that low species diversity of many of the putative relicts results from a lower rate of diversification than in dated Cape radiations. In other putative relicts, however, we cannot reject the possibility that they diversify at the same underlying rate as the radiations, but have been present in the Cape for insufficient time to accumulate higher diversity. Although the extremes in diversity of currently dated Cape lineages fall outside expectations under a constant underlying diversification rate, sampling of all Cape lineages would be required to reject this null hypothesis.


ExoMars Raman Laser Spectrometer: A Tool to Semiquantify the Serpentinization Degree of Olivine-Rich Rocks on Mars.
We evaluated the effectiveness of the ExoMars Raman laser spectrometer (RLS) to determine the degree of serpentinization of olivine-rich units on Mars. We selected terrestrial analogs of martian ultramafic rocks from the Leka Ophiolite Complex (LOC) and analyzed them with both laboratory and flight-like analytical instruments. We first studied the mineralogical composition of the samples (mostly olivine and serpentine) with state-of-the-art diffractometric (X-ray diffractometry [XRD]) and spectroscopic (Raman, near-infrared spectroscopy [NIR]) laboratory systems. We compared these results with those obtained using our RLS ExoMars Simulator. Our work shows that the RLS ExoMars Simulator successfully identified all major phases. Moreover, when emulating the automatic operating mode of the flight instrument, the RLS ExoMars Simulator also detected several minor compounds (pyroxene and brucite), some of which were not observed by NIR and XRD (e.g., calcite). Thereafter, we produced RLS-dedicated calibration curves (R2 between 0.9993 and 0.9995 with an uncertainty between ±3.0% and ±5.2% with a confidence interval of 95%) to estimate the relative content of olivine and serpentine in the samples. Our results show that RLS can be very effective in identifying serpentine, a scientific target of primary importance for the potential detection of biosignatures on Mars-the main objective of the ExoMars rover mission.


Ovarian Hemangiomas Do Not Harbor EWSR1 Rearrangements: Clinicopathologic Characterization of 10 Cases.
Hemangiomas of the ovary are rare with a majority described as individual reports of unusual clinical presentations or morphologic findings. Both the expected and unexpected pathologic features of these tumors in the ovary are not well detailed. Therefore, we collected the largest series of ovarian hemangiomas to comprehensively define their clinicopathologic associations and examine the significance of hormone receptors in their pathogenesis. In addition, a novel EWSR1-NFATC1 fusion has recently been described in a case of hemangioma of bone. To our knowledge, EWSR1 rearrangement has not been evaluated in hemangiomas of other sites or in a case series. Accordingly, we used fluorescence in situ hybridization to investigate EWSR1 status in a majority of our cases. Clinical presentation was variable and dependent on tumor size. Patient age ranged 48 to 87 yr (median 63 yr). Tumors involved the right (n=6) and left (n=3) ovaries with laterality unknown in 1 case, and size ranged from 0.2 to 5.0 cm (median 1.0 cm). Three of 4 radiologic reports were either equivocal or could not exclude malignancy. Seven cases were of the cavernous type and 3 were mixed cavernous and capillary type. All lesions formed a single discrete, circumscribed mass that displaced the surrounding cortical stroma. The cavernous type showed dilated, thin-walled vessels and vascular thrombi, some of which were associated with dystrophic calcification. In addition to cavernous morphology, the mixed form exhibited features of capillary hemangioma such as lobulated growth of capillary-sized vascular spaces that lacked atypia or multilayering and were linked to a larger feeding vessel. Each tumor expressed CD31, CD34, FLI-1, ERG, but not D240. The hemangioma stromal cells, but not endothelium, expressed estrogen and progesterone receptors in every case. Stromal luteinization was seen in 2 cases. Follow-up ranged 1 to 139 mo and all patients were disease free. All cases were negative for EWSR1 rearrangement; however, 2 cases demonstrated additional intact copies of EWSR1 indicating aneusomy 22 or a structural abnormality of chromosome 22 resulting in apparent duplication of the EWSR1 gene region (at 22q12). Although an uncommon entity, awareness of ovarian hemangioma's unique and diverse clinical presentation as well as its potential to radiologically imitate malignant ovarian neoplasms are important.


Primary glomerulonephritis: an update on renal survival and determinants of progression.
Few epidemiological studies have investigated the long-term outcome of primary glomerulonephritis (GN) and its determinants in the decade since angiotensin-converting enzyme inhibitors entered widespread use. To study several traditional and less traditional risk factors for kidney disease progression in a cohort of patients with primary GN. Retrospective cohort study. We included 536 patients with primary GN first diagnosed between 1994 and 2001: 283 IgA nephropathy (IgA), 129 membranous nephropathy (MN), and 124 focal and segmental glomerulosclerosis (FSGS). Adjusted hazard ratios (HR) or dialysis or preemptive transplantation for end-stage renal disease (ESRD) according to various characteristics were estimated with Cox proportional-hazard models. At diagnosis, mean patient age was 43 +/- 17 years, 74% were men, and the mean estimated glomerular filtration rate (eGFR) was 69 +/- 31 mL/mn/1.73m(2). After a mean follow-up of 7-years, 104 patients had started ESRD treatment and 14 had died before reaching ESRD. The 7-year renal survival rate was 69% for FSGS, 88% for MN, and 82% for IgAN (p < 0.01). In patients with FSGS, younger age was associated with a higher risk of ESRD. Baseline proteinuria, diabetes, and haemoglobin (Hb) concentration were strongly associated with shorter time to ESRD independent of baseline eGFR, but gender, hypertension and smoking were not. Adjusted HRs for ESRD were 2.6 [95% confidence interval, 1.2-5.8] for diabetes and 2.4 [1.3-4.5] for the lowest and 1.9 [1.0-3.6] for the intermediate Hb tertiles versus the highest. In patients with primary GN, renal survival is clearly lower for FSGS than for IgAN and MN. Independent predictors for progression were baseline diabetes and anaemia, as well as proteinuria, for all GN types, and younger age, for FSGS.


Rapid assessment of road safety policy change: relaxation of the national speed enforcement law in Russia leads to large increases in the prevalence of speeding.
Reducing vehicle speed is among the most effective road safety strategies. We assess how a new policy in Russia that eliminates fines for driving up to 20 km/h above the speed limit has affected the prevalence of speeding. We measured speeds periodically in 13 districts of two Russian regions during 2011-2013 and analysed the effect of the policy using difference-in-differences to control for seasonality. We find that the prevalence of speeding was declining steadily but half of the gains since mid-2011 were lost immediately after the new policy. Overall speeding increased significantly by 13 percentage points (pp, 95% CI 4 to 19). Speeding more than 10 km/h above the limit increased significantly by 10 pp (95% CI 2 to 12), and extreme speeding increased but not significantly (1.7 pp, 95% CI -1.1 to 4.5). Road traffic injuries will likely increase in Russia unless speeding fines are reinstated.


Life's Simple 7 at Midlife and Risk of Recurrent Cardiovascular Disease and Mortality after Stroke: The ARIC study.
Stroke is a leading cause of morbidity and mortality among adults in the U.S. Ideal levels of the Life's Simple 7 (LS7) are associated with lower cardiovascular disease (CVD) and all-cause mortality. However, the association of LS7 with CVD, recurrent stroke, and all-cause mortality after incident stroke is unknown. We used data from the ARIC study, a cohort of 13,508 adults from four US communities, 45-64 years old at baseline (1987-1989). Cardiovascular hospitalizations and mortality were ascertained in follow-up through December 31st, 2017. We defined cardiovascular health (CVH) based on AHA definitions for LS7 (range 0-14) and categorized CVH into four levels: LS7 0-3, 4-6, 7-9, and ≥10 (ideal LS7), according to prior studies. Outcomes included incident stroke, CVD, recurrent stroke, all-cause mortality, and a composite outcome including all the above. Adjusted hazard ratios (95% CI) were estimated with Cox proportional hazards regression models. Median (25%-75%) follow-up for incident stroke was 28 (18.6-29.2) years. Participants with incident stroke were 55.7 (SD 5.6) years-old at baseline, 53% were women and 35% Black. Individuals with LS7 score ≥10 had 65% lower risk (HR: 0.35; 95% CI: 0.29-0.41) of incident stroke than those with LS7 4-6 (reference group). Of 1,218 participants with incident stroke, 41.2% (n=502) had composite CVD and 68.3% (n=832) died during a median (25%-75%) follow-up of 4.0 (0.76-9.95) years. Adjusted HR (95% CI) for stroke survivors with LS7≥10 at baseline were 0.74 (0.58-0.94) for the composite outcome, 0.38(0.17-0.85) for myocardial infarction, 0.60 (0.40-0.90) for heart failure, 0.63 (0.48-0.84) for all-cause mortality, and 0.65 (0.39-1.08) for recurrent stroke. Good and excellent midlife cardiovascular health are associated with lower risks of incident stroke and CVD after stroke. Clinicians should stress the importance of a healthy lifestyle for primary and secondary CVD prevention.


Frequent hemodialysis and psychosocial function.
Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.


Suspected neonatal isoerythrolysis in two Baird's tapirs (Tapirus bairdii).
Two Baird's tapir (Tapirus bairdii) calves born at the Columbus Zoo from the same sire and dam developed hemolytic anemia that was consistent in history and clinical signs with neonatal isoerythrolysis (NI). One calf developed severe, fatal hemolytic anemia after being fed maternal colostrum, and the other developed moderate hemolytic anemia after being fed equine colostrum. No cross-reactivity was demonstrated between sire and dam blood samples, and both tapirs possessed serum antibodies reactive against equine blood group Ca and antigens reactive with several equine blood group D antibodies. Electrophoresis demonstrated significant genetic diversity between tapir and equine blood proteins. Agglutination testing demonstrated strong reactivity between a far greater percentage of equine colostrum samples when tested against sire and dam tapir blood (61% and 65%, respectively) than would be expected for equine blood (2%). These data are suggestive of a diagnosis of NI but are not definitive. Further study is required to determine whether NI occurs in tapirs and whether equine colostrum is harmful to tapir calves.


Review of genotoxicity studies of glyphosate and glyphosate-based formulations.
An earlier review of the toxicity of glyphosate and the original Roundup™-branded formulation concluded that neither glyphosate nor the formulation poses a risk for the production of heritable/somatic mutations in humans. The present review of subsequent genotoxicity publications and regulatory studies of glyphosate and glyphosate-based formulations (GBFs) incorporates all of the findings into a weight of evidence for genotoxicity. An overwhelming preponderance of negative results in well-conducted bacterial reversion and in vivo mammalian micronucleus and chromosomal aberration assays indicates that glyphosate and typical GBFs are not genotoxic in these core assays. Negative results for in vitro gene mutation and a majority of negative results for chromosomal effect assays in mammalian cells add to the weight of evidence that glyphosate is not typically genotoxic for these endpoints in mammalian systems. Mixed results were observed for micronucleus assays of GBFs in non-mammalian systems. Reports of positive results for DNA damage endpoints indicate that glyphosate and GBFs tend to elicit DNA damage effects at high or toxic dose levels, but the data suggest that this is due to cytotoxicity rather than DNA interaction with GBF activity perhaps associated with the surfactants present in many GBFs. Glyphosate and typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.


Symptom Relief and Retreatment After Vaginal, Open, or Robotic Surgery for Apical Vaginal Prolapse.
The aim of this work was to determine the degree of symptom relief and survival free of retreatment after Mayo-McCall culdoplasty (MMC), open abdominal sacrocolpopexy (ASC), and robotic sacrocolpopexy (RSC) for posthysterectomy vaginal vault prolapse. We retrospectively studied patients who had undergone surgery for posthysterectomy apical vaginal prolapse from January 1, 2000, through June 30, 2012, at our institution. Baseline characteristics and perioperative outcomes were abstracted from electronic health records. Cross-sectional data for current pelvic floor symptoms were collected by using validated questionnaires. Survival free of retreatment was estimated with the Kaplan-Meier method. To account for selection bias, adjusted analyses using inverse probability weighting (IPW) were performed to compare outcomes for MMC versus ASC, MMC versus RSC, and ASC versus RSC. Of 512 patients, 337 completed at least a validated or abbreviated questionnaire. Among MMC, ASC, and RSC groups, overall Pelvic Floor Distress Inventory 20, Pelvic Floor Impact Questionnaire Short Form 7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire 12 summary scores were not significantly different. There was no significant difference in 5-year survival free of retreatment for MMC (94.0%) versus RSC (95.5%) and ASC (94.8%) versus RSC (92.1%). However, patients who had MMC were more likely to have retreatment than patients who had ASC during the first 10 years (10-year survival free of retreatment: 81.1% vs 95.4%; hazard ratio, 3.68 [95% confidence interval, 1.51-8.98]); the 10-year data were not available for RSC comparisons, given the later initiation of RSC. Symptom relief was comparable after MMC, ASC, and RSC. Among all groups, most patients were free of retreatment for prolapse at 5 years. Between the MMC and ASC groups, survival free of retreatment (%) within 10 years was still favorable, but ASC had greater durability, particularly after accounting for selection bias.


[A case of brachial amyotrophic diplegia accompanied with Sjögren's syndrome presenting good response to immunotherapies in the early course of the disease].
A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sjögren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sjögren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies.


Recognition of clinical deterioration: a clinical leadership opportunity for nurse executive.
Recognition and avoidance of further clinical deterioration can be termed a critical success factor in every care delivery model. As care resources become more constrained and allocated to the most critical of patients, some patients are being shifted to less intense and costly care settings where continuous physiologic monitoring may not be an option. Nurse executives are facing these complex issues as they work with clinical experts to develop systems of safety in the patient care arena. A systematic review of the literature related to the recognition of clinical deterioration is needed to identify areas for further leadership, research, and practice advancements.


Pbx-1 Hox heterodimers bind DNA on inseparable half-sites that permit intrinsic DNA binding specificity of the Hox partner at nucleotides 3' to a TAAT motif.
Heterodimers between the Pbx/Exd and Hox/HOM-C classes of homeodomain proteins bind regulatory elements in tissue-specific and developmentally regulated genes. In this work, we characterize the half-site bound by both Pbx1 and Hox proteins on a prototypic element (TGATTAAT) and determine how the orientation of the Hox protein contributes to the DNA binding specificity of Pbx-Hox heterodimers. We demonstrate that the Hox protein binds the 3' TAAT sequence as its recognition core and exhibits sequence-specific binding at positions 3' to the TAAT core. Unfavored sequences at this position, such as two cytosines, abrogate binding to the element. The upstream Pbx1 core sequence, TGAT, must immediately juxtapose the Hox core. This geometry maintains the preference of Hox/HOM-C proteins for a T base at position -1, as T represents the fourth position of the Pbx1 core, and suggests that this T base is bound by both Pbx1 and Hox proteins, Pbx1 binding in the major grove and the Hox protein binding in the minor grove. Pbx1 also exhibits base selectivity 5' to its TGAT recognition sequence.


Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency.
The present paper reports biochemical and neurophysiological investigations in ten cases with restless leg syndrome. Other neuropsychiatric affections and factors which could generate the symptomatology of restless legs syndrome were not included. The EEG recordings demonstrated evident reticular neuronal hypersynchrony generated by hyperpnoea (sinusoidal slow waves). The classical EEG investigations pointed out neuromuscular hyperexcitability, but some modifications of the functional parameters of the neuromuscular excitability and conductibility (signs of neuropathy) were also noticed. In all the cases, continuous 8-hour polysomnographic recordings and monitorization on infrared TV screen were performed. Investigations reported: important disorders of sleep organization, agitated sleep with frequent periods of nocturnal awakenings, increase of the durations and percentages of light slow-wave sleep (LSWS) and rapid and frequent changes of various stages of LSWS, a decrease of duration and percentage of DSWS, a decrease of duration and percentage of REM sleep (as in other parasomnias caused by magnesium deficiency) and nocturnal EEG anomalies (long discharges of sinusoidal slow waves, of sharp waves and of sharp slow waves appearing in the LSWS stages with the disappearance in the REM sleep).


All-ceramic, bi-layered crowns supported by zirconia implants: Three-year results of a prospective multicenter study.
To determine the clinical and patient-reported outcomes of bi-layered, all-ceramic posterior single crowns (SCs) supported by zirconia implants in an uncontrolled, prospective, multicenter study. In two centers, 60 patients received 71 one-piece zirconia oral implants to be restored with either SCs (n=49) or three-unit fixed dental prostheses (n=11). Of these patients, 45 implants were restored with all-ceramic, zirconia-based posterior SCs (one per patient). Survival rates of implants and reconstructions were assessed, and technical success was evaluated according to modified U.S. Public Health Service (USPHS) criteria. Furthermore, patient-reported outcome measures (PROMs) were assessed by applying visual analog scales (VAS). Kaplan-Meier (KM) plots and log-rank tests were used for success/survival analyses. The Wilcoxon matched-pairs signed-rank test was used to evaluate time effects on response variables (PROMs, USPHS criteria). Forty patients with 40 SCs could be evaluated after 36.7±1.2months. No SC was replaced, resulting in 100% survival. The KM success estimate was 87.5% (two chippings, one restoration margin, and one contour were rated Charlie). In general, the incidence of chipping (p=.0005) and occlusal roughness (p=.0003) was frequent. Compared with the pre-treatment patient surveys (67-93%), all surveys at prosthetic delivery except for speech (p=.139) showed significantly improved VAS scores (81-94%; p<.0001). Thereafter, no decrease in satisfaction could be observed over time until the 3-year follow-up (86-93%; p≥.390). Veneered, zirconia-based SCs supported by zirconia implants satisfied patients' needs highly. However, significant incidence of chipping and roughness of the veneering ceramic may compromise the clinical long-term outcome for this indication. Posterior, zirconia-based SCs supported by zirconia oral implants entirely survived the follow-up period of 3 years, but two major chippings, one a significant marginal opening and one pronounced over-contouring, resulted in a reduced KM success estimate of 87.5% after 36 months of observation.


[Effect of drugs of the fluoroquinolone series on morphokinetic parameters of the cellular elements of lung tissue].
The effect of various concentrations of ofloxacin, ciprofloxacin and lomefloxacin on the morphokinetic parameters of the cellular elements of the lung tissue of intact animals (mice, guinea pigs and dogs) was studied under the conditions of the tissue culture. It was shown that in a concentration of 100 micrograms/ml and the exposure time of 24 hours the drugs had no effect on the mobility and structure of the lung tissue cellular elements. When the drugs were used in a concentration of 100 micrograms/ml the mobility rate of the lymphocytes and macrophages proved to by markedly retarded by the end of the 24th hour. In a concentration of 1000 micrograms/ml the drugs killed the cell culture. There were detected no specific differences in the effect of the fluoroquinolones on the cellular elements of the lung tissue of the intact animals.


Focusing errors in a collimating lens or mirror: use of a moiré technique.
The Fresnel diffraction pattern of a grating periodically gives an exact reproduction of the grating. By superposing a second grating on such an image, we form a moiré pattern that depends upon the degree of parallelism of the incident beam. We present here the possibility of using this technique for studying the focusing errors in a collimating lens or a mirror.


VARYING COEFFICIENT MODELS FOR DATA WITH AUTO-CORRELATED ERROR PROCESS.
Varying coefficient model has been popular in the literature. In this paper, we propose a profile least squares estimation procedure to its regression coefficients when its random error is an auto-regressive (AR) process. We further study the asymptotic properties of the proposed procedure, and establish the asymptotic normality for the resulting estimate. We show that the resulting estimate for the regression coefficients has the same asymptotic bias and variance as the local linear estimate for varying coefficient models with independent and identically distributed observations. We apply the SCAD variable selection procedure (Fan and Li, 2001) to reduce model complexity of the AR error process. Numerical comparison and finite sample performance of the resulting estimate are examined by Monte Carlo studies. Our simulation results demonstrate the proposed procedure is much more efficient than the one ignoring the error correlation. The proposed methodology is illustrated by a real data example.


[Features of immunogenesis in simians infected with attenuated strains of tick-borne encephalitis and Langat virus].
Certain parameters of humoral and cellular immunity induced by attenuated tick-borne encephalitis (TBE) and Langat virus strains were studied in monkeys. The immunogenic activity of the strains inoculated subcutaneously and intracerebrally was manifested by two processes: synthesis of specific antibody and cellular immune response. The highest titers of humoral immunity in N, HI, and CF tests were observed to homologous viruses. The immune response to both homologous and heterologous viruses could be optimized by increasing the number of antigenic stimulations. The sequence of antibody synthesis of the macro- and microglobulin series was similar in monkeys infected with virulent and attenuated strains. Cellular immunity reactions were detected and changes in the quantity and functional activity of T- and B-lymphocytes were determined. Most marked immunological changes were observed with the virulent TBE virus strain as compared with naturally and experimentally attenuated Langat virus strains.


Hybrid peripheral nerve sheath tumors: report of five cases and detailed review of literature.
Hybrid peripheral nerve sheath tumors (PNSTs) have been recognized recently and were first included in the 4th edition of World Health Organization (WHO) Classification of Tumors of Soft tissue and Bone, published in 2013. These tumors show combined features of more than one type of conventional benign peripheral nerve sheath tumors. The most common combinations are those of schwannoma/perineurioma followed by combinations of neurofibroma/schwannoma and neurofibroma/perineurioma. A detailed literature review of published cases is presented. We have discussed the types and etiology, epidemiology and sites of localization, gross and microscopic appearances and immunohistochemical features of hybrid PNSTs and association of these tumors with tumor syndromes. We have included five cases which were diagnosed in our department as we believe that publication of these new cases is relevant for the improved understanding of these specific tumors. Four of our five patients were males, mean age was 24 years. There was wide variation in the location of these tumors. Mean size of excised tumors was 5.5 cms in the greatest dimensions. Three out of five cases represented hybrid schwannoma/perineurioma histologically. No significant nuclear atypia, mitotic activity or necrosis seen. All five cases were completely excised. All five patients are alive and well at the time of writing with no recurrence. Hybrid PNSTs are distinct tumors and are usually benign. However, rare case reports have described local recurrence and at least two recent case reports have described malignant transformation in these tumors. Further studies on large number of cases are required to determine the exact pathogenetic basis of these tumors.


Population-based analysis of colorectal cancer risk after oophorectomy.
The development of colorectal cancer is influenced by hormonal factors. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. The aim of this cohort study was to examine colorectal cancer risk after oophorectomy for benign indications. Women who had undergone oophorectomy between 1965 and 2011 were identified from the Swedish Patient Registry. Standard incidence ratios (SIRs) and 95 per cent confidence intervals for colorectal cancer risk were calculated compared with those in the general population. Stratification was carried out for unilateral and bilateral oophorectomy, and hysterectomy without specification of whether the ovaries were removed or not. Associations between the three oophorectomy options and colorectal cancer risk in different locations were assessed by means of hazard ratios (HRs) and 95 per cent confidence intervals calculated by Cox proportional hazards regression modelling. Of 195 973 women who had undergone oophorectomy, 3150 (1·6 per cent) were diagnosed with colorectal cancer at a later date (median follow-up 18 years). Colorectal cancer risk was increased after oophorectomy compared with that in the general population (SIR 1·30, 95 per cent c.i. 1·26 to 1·35). The risk was lower for younger age at oophorectomy (15-39 years: SIR 1·10, 0·97 to 1·23; 40-49 years: SIR 1·26, 1·19 to 1·33; P for trend < 0·001). The risk was highest 1-4 years after oophorectomy (SIR 1·66, 1·51 to 1·81; P < 0·001). In the multivariable analysis, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had only unilateral oophorectomy (HR 2·28, 95 per cent c.i. 1·33 to 3·91). Colorectal cancer risk is increased after oophorectomy for benign indications.


Novel individual metabolic profile characterizes the protein kinase B-alpha (pkbα-/-) in vivo model.
Type 2 diabetes and associated co-morbidities run epidemic waves worldwide. Since pathophysiological constellations are individual and display a wide spread of dysmetabolic profiles personalized health care assessments start to emerge. Therefore, we established a specific in silico assessment tool targeting metabolic characterizations individually. Values obtained from oral glucose and intraperitoneal insulin tolerance tests performed on pkbα(-/-) mice (KO) as well as age- and gender-matched controls (WT) were analysed using our established in silico model. Generally, male pkbα(-/-) mice (KO) presented significantly increased insulin sensitivity at an age of 6 months compared with age-matched WTs (p = 0.036). Female KO and WT groups displayed improved glucose sensitivities compared with age-matched males (for WT p ≤ 0.011). Specific metabolic characterization should be assessed individually. Therefore, our in silico model enables novel insights inaugurating specific primary preventive strategies targeting individual metabolic profiling precisely.


Molecular phylogeny of the superorder Archonta.
The superorder Archonta has been hypothesized to include primates, tree shrews, bats, and flying lemurs as descendants of a common ancestor. More recently, a diphyletic origin for bats has been proposed. To evaluate these hypotheses, the nucleotide sequence of the mitochondrial cytochrome oxidase subunit II gene was determined from a bushbaby (Galago senegalensis), flying lemur (Cynocephalus variegatus), tree shrew (Tupaia glis), spear-nosed bat (Phyllostomus hastatus), rousette bat (Rousettus leschenaulti), and nine-banded armadillo (Dasypus novemcinctus) and was compared with published sequences of a human, cow, and mouse. Phylogenetic analyses of the sequences give evidence that primates, tree shrews, and flying lemurs have a recent common ancestor but that bats are genealogically distant. The monophyletic origin of bats is supported. Contrary to interpretations based on morphological data, tree shrews are shown to be no more closely affiliated with primates than are flying lemurs. Analyses of the cytochrome oxidase subunit II gene give marginally more support to a Dermoptera-Scandentia clade than to a Dermoptera-Primates clade.


Family carers' perspectives on post-school transition of young people with intellectual disabilities with special reference to ethnicity.
School leavers with intellectual disabilities (ID) often face difficulties in making a smooth transition from school to college, employment or more broadly to adult life. The transition phase is traumatic for the young person with ID and their families as it often results in the loss of friendships, relationships and social networks. The aim of this study was to explore the family carers' views and experiences on transition from school to college or to adult life with special reference to ethnicity. Forty-three families (consisting of 16 White British, 24 Pakistani, 2 Bangladeshi and one Black African) were interviewed twice using a semi-structured interview schedule. The carers were interviewed twice, Time 1 (T1) and Time 2 (T2), T2 being a year later to observe any changes during transition. The findings indicate that although transition planning occurred it was relatively later in the young person's school life. Parents were often confused about the process and had limited information about future options for their son or daughter. All family carers regardless of ethnicity, reported lack of information about services and expressed a sense of being excluded. South Asian families experienced more problems related to language, information about services, culture and religion. The majority of families lacked knowledge and awareness of formal services and the transition process. Socio-economic status, high levels of unemployment and caring for a child with a disability accounted for similar family experiences, regardless of ethnic background. The three key areas relevant for ethnicity are interdependence, religion and assumptions by service providers.


Revision of haemotrophic Mycoplasma species names.
The recently proposed transfer of four rickettsias from the genera Haemobartonella and Eperythrozoon to the genus Mycoplasma with the Candidatus status is herein revised. This is because the Candidatus designation is for new, incompletely described taxa, in order to give them a provisional status. Thus, 'Candidatus Mycoplasma haemofelis' is revised to Mycoplasma haemofelis comb. nov., nom. nov., 'Candidatus Mycoplasma haemomuris' is revised to Mycoplasma haemomuris comb. nov., nom. nov., 'Candidatus Mycoplasma haemosuis' is revised to Mycoplasma haemosuis comb. nov., nom. nov. and 'Candidatus Mycoplasma wenyonii' is revised to Mycoplasma wenyonii comb. nov.


Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance angiography.
We reviewed 1440 MRA studies to identify patients with middle cerebral artery stenosis (MCAS). We identified 99 cases, and after reviewing the clinical records, classified 28 as asymptomatic MCAS (AMCAS), a prevalence of 2%. Suspected stroke was the most frequent indication for MRA. Follow-up was available for 21, mean 46.7 months (range 2.4-75.6 months). One stroke occurred in the AMCAS territory (5%), other strokes in five patients (24%). There were five deaths in patients with MCAS; age > 69 (P = 0.045) was the only associated risk factor. This study suggests that patients in whom MRA is performed and shows AMCAS may be at increased risk of strokes in any vascular distribution or of death.