Fission yeast shelterin regulates DNA polymerases and Rad3(ATR) kinase to limit telomere extension.
Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR)/Tel1(ATM)-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT)), DNA polymerases, Replication Protein A (RPA) complex, Rad3(ATR)-Rad26(ATRIP) checkpoint kinase complex, Tel1(ATM) kinase, shelterin subunits (Tpz1, Ccq1 and Poz1) and Stn1. We further investigated how telomere shortening, caused by trt1Δ or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Polε) and lagging (Polα) strand DNA polymerases at telomeres to modulate Rad3(ATR) association, Ccq1 Thr93 phosphorylation and telomerase recruitment.


Melanoma-specific survival is worse in the elderly: a multicentric cohort study.
We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P < 0.001), as were nodular melanoma and acral lentiginous melanoma ( P < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan-Meier survival curves showed longer melanoma-specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.


Whole Proteome Analyses on Ruminiclostridium cellulolyticum Show a Modulation of the Cellulolysis Machinery in Response to Cellulosic Materials with Subtle Differences in Chemical and Structural Properties.
Lignocellulosic materials from municipal solid waste emerge as attractive resources for anaerobic digestion biorefinery. To increase the knowledge required for establishing efficient bioprocesses, dynamics of batch fermentation by the cellulolytic bacterium Ruminiclostridium cellulolyticum were compared using three cellulosic materials, paper handkerchief, cotton discs and Whatman filter paper. Fermentation of paper handkerchief occurred the fastest and resulted in a specific metabolic profile: it resulted in the lowest acetate-to-lactate and acetate-to-ethanol ratios. By shotgun proteomic analyses of paper handkerchief and Whatman paper incubations, 151 proteins with significantly different levels were detected, including 20 of the 65 cellulosomal components, 8 non-cellulosomal CAZymes and 44 distinct extracytoplasmic proteins. Consistent with the specific metabolic profile observed, many enzymes from the central carbon catabolic pathways had higher levels in paper handkerchief incubations. Among the quantified CAZymes and cellulosomal components, 10 endoglucanases mainly from the GH9 families and 7 other cellulosomal subunits had lower levels in paper handkerchief incubations. An in-depth characterization of the materials used showed that the lower levels of endoglucanases in paper handkerchief incubations could hypothetically result from its lower crystallinity index (50%) and degree of polymerization (970). By contrast, the higher hemicellulose rate in paper handkerchief (13.87%) did not result in the enhanced expression of enzyme with xylanase as primary activity, including enzymes from the "xyl-doc" cluster. It suggests the absence, in this material, of molecular structures that specifically lead to xylanase induction. The integrated approach developed in this work shows that subtle differences among cellulosic materials regarding chemical and structural characteristics have significant effects on expressed bacterial functions, in particular the cellulolysis machinery, resulting in different metabolic patterns and degradation dynamics.


Dose-Response Relationships between Levels of Alcohol Use and Risks of Mortality or Disease, for All People, by Age, Sex, and Specific Risk Factors.
Alcohol use has been causally linked to more than 200 disease and injury conditions, as defined by three-digit ICD-10 codes. The understanding of how alcohol use is related to these conditions is essential to public health and policy research. Accordingly, this study presents a narrative review of different dose-response relationships for alcohol use. Relative-risk (RR) functions were obtained from various comparative risk assessments. Two main dimensions of alcohol consumption are used to assess disease and injury risk: (1) volume of consumption, and (2) patterns of drinking, operationalized via frequency of heavy drinking occasions. Lifetime abstention was used as the reference group. Most dose-response relationships between alcohol and outcomes are monotonic, but for diabetes type 2 and ischemic diseases, there are indications of a curvilinear relationship, where light to moderate drinking is associated with lower risk compared with not drinking (i.e., RR < 1). In general, women experience a greater increase in RR per gram of alcohol consumed than men. The RR per gram of alcohol consumed was lower for people of older ages. RRs indicated that alcohol use may interact synergistically with other risk factors, in particular with socioeconomic status and other behavioural risk factors, such as smoking, obesity, or physical inactivity. The literature on the impact of genetic constitution on dose-response curves is underdeveloped, but certain genetic variants are linked to an increased RR per gram of alcohol consumed for some diseases. When developing alcohol policy measures, including low-risk drinking guidelines, dose-response relationships must be taken into consideration.


A Rare Case of Vascular Ring and Coarctation of the Aorta in Association with CHARGE Syndrome.
A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring-consisting of a right aortic arch with retroesophageal brachiocephalic artery-combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution. To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case of these combined disorders occurring in CHARGE syndrome. This report describes a truly rare case and reveals the limitations of echocardiography in detecting complex aortic arch anomalies while illustrating the benefits of advanced imaging prior to surgical intervention.


Guillain-Barré syndrome: an Italian multicentre case-control study. Guillain-Barré Syndrome Study Group.
Various diseases are described as antecedents of Guillain-Barré syndrome (GBS), particularly gastroenteritis and respiratory infectious diseases, but epidemiological surveys are rare. This paper details a multicentre matched case-control study carried out within a well-defined Italian population. For each GBS case fulfilling the Asbury and Cornblath criteria, one control was recruited from a neurological (NC) ward and another from a non-neurological (NNC) ward, matched for age, sex, season of disease onset and area of residence. All cases and controls were administered a semistructured questionnaire. The OR was calculated according to the Mantel-Haenszel equation for triplets. Between 1 October 1996 and 30 September 1998, 75 triplets were included in the case-control study. The OR for flu-like syndrome was 7.14 (CI 95%, 3.28-15.52) and for gastroenteritis 3.57 (CI 95%, 1.31-9.72); no other factor reached significance. Our results, based on the clinical and anamnestic features of triplets of patients, support the possible role as risk factors for GBS of infectious diseases, particularly flu-like syndrome and gastroenteritis.


Influence of LC retention data on antitumor acridinones' classification evaluated by factor analysis method.
The application of factor analysis (FA) method in classification of the antitumor acridinones based on high-performance liquid chromatography (HPLC) retention data and calculated parameters of lipophilicity as well as some nonempirical structural parameters was studied. First, a group of 19 acridinone (imidazoacridinone and triazoloacridinone) derivatives was chromatographed in six RP-HPLC systems, and the values of their HPLC retention data as retention' times determined in both 10 min and 30 min gradient times were obtained as well as log kw (retention factor log k extrapolated to 0% organic modifier) parameters using DryLab program were calculated. Additionally, molecular modeling studies were performed based on the structural formula of considered acridinones and structural descriptors were derived as well as log P parameters using some commonly available software were calculated and subsequently used. A matrix of 19 x 32 HPLC data together with log P data and molecular properties parameters was subjected to factor analysis and led to extract three main factors with eigenvalues higher than 1. The first principal component (factor 1) accounted for, by 80.87% of the variance in data, the second principal component (factor 2) explained 7.77% and the third principal component (factor 3) was responsible by 4.46% of data variance. The total data variance was at the level 93.09% and was explained by the first three principal components. Moreover, one of the most significant influences on the values of factor 1 and factor 2 possessed HPLC retention data and calculated parameters describing lipophilicity, respectively. More importantly, distribution of individual drugs on the plane determined by two principal components produced patterns in good agreement with their chemical structures as well as with their antitumor activity.


Auditory outcomes after scala vestibuli array insertion are similar to those after scala tympani insertion 1 year after cochlear implantation.
In cochlear implantation, a scala vestibuli (SV) insertion of an electrode array is a rare occurrence and is reported to be linked to poor hearing outcomes. Using the same electrode array, the auditory performance of patients with a complete SV location was compared with that of patients having a complete scala tympani (ST) location 1 year after implantation. Thirty-three patients were included in this retrospective case-control study (SV, n = 12; ST, n = 21). The matching criteria were electrode array type, age at implantation, and duration of severe or profound deafness. The array location was analyzed using 3D reconstruction of postoperative CT scans. Postoperative audiological evaluation of the implanted ear was performed using pure-tone audiometry, speech recognition of monosyllabic words in quiet, and words and sentences in noise. On the preoperative CT scan, six patients in the SV group presented with both round window (RW) and ST ossification, three with RW ossification alone, and three with no RW ossification. Auditory performance did not differ between SV and ST groups 1 year after cochlear implantation. Speech recognition of words was 49 ± 7.6% and 56 ± 5.0% in quiet and 75 ± 9.5% and 66 ± 6.0% in noise in SV and ST groups, respectively. ST insertion is the gold standard that allows the three cochlear scalae to preserve scalar cochlear integrity. However, 1 year after implantation, a planned or unexpected SV insertion is not detrimental to hearing outcomes, providing similar auditory performance in quiet and noise to ST insertion.


Mature and Immature Solid Teratomas Involving Uterine Corpus, Cervix, and Ovary.
Extragonadal teratomas are rare, and localization in the endometrium and cervix is exceptional, with fewer than 10 case reports documented so far in the English literature. We report here the case of a 46-year-old patient who presented with simultaneous immature teratoma in the endometrium and mature teratomas in the ovary in association with gliomatosis peritonei but with no evidence of gestational origin; she subsequently developed multiple solid mature teratomas in the cervix and parauterine tissue. No other similar cases have been previously reported to our knowledge. There are many similarities between the patient's pattern of recurrence and "growing teratoma syndrome (GTS)". Although the patient was not treated with chemotherapy after her first presentation and this case does not meet formal criteria for GTS, we believe that the pattern and histology of recurrences in this case represent a variant of GTS. Considering that the initial presentation in this case was endometrial and ovarian makes the occurrence of GTS-like syndrome even more unique.


Isolated laparoscopic resection of the hepatic caudate lobe: surgical technique and a report of 2 cases.
The caudate lobe of the liver, segment 1 (S1), is located between the hepatic hilum and the inferior vena cava. Resection of S1 alone, without sacrificing other parts of the liver, is a surgical challenge. We present 2 cases of isolated laparoscopic resections of hepatic S1. We are the first to describe this laparoscopic technique. Two patients affected by colorectal liver metastases confined to S1 underwent laparoscopic isolated resections of S1 using a left approach. One of them also underwent left lateral segmentectomy. Both interventions were accomplished laparoscopically without conversion. Operative time for the first patient was 150 minutes and that for the second patient was 105 minutes. Blood loss was 200 and 100 mL for the first and second patients, respectively. There were no major intraoperative complications except for a tear in the inferior vena cava in the first patient that was repaired without the need for conversion. The postoperative course was uneventful for both patients. The duration of hospital stay was 10 and 8 days, respectively. The resected margins of the specimens were tumor-free (R0 resections). The 2 patients are alive and disease-free 7 and 5 months after the procedure. Isolated laparoscopic resection of the hepatic caudate lobe can be performed by a highly skilled surgeon, but should be performed only in selected cases.


Differential expression of endoglin in human melanoma cells expressing the V3 isoform of versican by microarray analysis.
Versican is a large chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The large isoforms V0 and V1 promote melanoma cell proliferation. We previously described that overexpression of the short V3 isoform in MeWo human melanoma cells markedly reduced tumor cell growth in vitro and in vivo, but favored the appearance of secondary tumors. This study aimed to elucidate the mechanisms of V3 by identifying differentially expressed genes between parental and V3-expressing MeWo melanoma cells using microarray analysis. V3 expression significantly reduced the expression of endoglin, a transforming growth factor-β superfamily co-receptor. Other differentially expressed genes were VEGF and PPP1R14B. Changes in endoglin levels were validated by qRT-PCR and Western blotting.


Comparison of different washing treatments for reducing pathogens on orange surfaces and for preventing the transfer of bacterial pathogens to fresh-squeezed orange juice.
The objectives of this study were to compare the effectiveness of various washing treatments for reducing Escherichia coli O157:H7, Salmonella sp., and Listeria monocytogenes populations on orange surfaces and to measure the effect of some of these treatments in preventing the transfer of pathogens during juice extraction. Orange surfaces inoculated with L. monocytogenes or a mixture of E. coli O157:H7 and Salmonella Typhimurium were washed by water spray and then sprayed with or dipped in water at 80°C for 1 min, 70% ethanol for 15, 30, or 45 s or 1, 2, or 4 min, 2 or 4% lactic acid solution at 55°C for 15, 30, or 45 s or 1, 2, or 4 min, or 200 mg/liter hypochlorite at pH 6.5 or 10 for 15 s. The surviving populations of these pathogens on the oranges were enumerated after each treatment. In a further stage, the ability of these pathogens to be transferred to the juice during extraction was tested. Juice was obtained from inoculated oranges that were subjected to selected treatments using chlorine, lactic acid, ethanol, and hot water as described above, and then bacterial counts in orange juice were determined. The application of these treatments reduced the populations of pathogens on orange surfaces by 1.9 to >4.9 log, 1.9 to >4.6 log, and 1.4 to 3.1 log cycles for E. coli O157:H7, Salmonella Typhimurium, and L. monocytogenes, respectively. The treatments using hot water or lactic acid showed greater reductions than other treatments. The time, antimicrobial concentration, and form of application affected the bacterial reduction. All treatments resulted in undetectable counts in the juice. Nevertheless, pathogens were recovered by the enrichment-plating method. Treatment of oranges before juice extraction may reduce the risk associated with consuming orange juice.


If you would enjoy your practice....
A mechanical or routinized approach to the care of patients is dulling to the physician and may foster burnout. The original goals of most physicians--continued learning and the helping of others--are more likely to be achieved if a process of active listening is included in their therapeutic armamentarium.


[Vitamin D: important from before the cradle and to the grave].
Approximately one hundred years ago, vitamin D was recognized as being important for bone health. Nowadays there is increasing evidence that even before birth as well as during lifetime, vitamin D plays a role in the prevention of several chronic diseases as well as cancer. Human beings depend on exposure to the sun to satisfy their daily requirements of vitamin D. Moreover, most doctors in the Netherlands are unaware that the production of vitamin D only takes place in the spring and summertime in the Dutch climate. One Dutch study reports hypovitaminosis D not only in more than half of non-western immigrant mothers and their newborns, but also in 10% of the western mothers and their babies. On a worldwide level, numerous studies report low vitamin-D status in western countries due to our modern way of living, the immigration of dark-skinned people to higher latitudes and the homebound elderly. For some years now the scientific world has called for action on this point; something that in practice appears to be difficult to achieve. Aiming for optimal vitamin-D levels means suppletion either through tablets or food fortification. In general, people do not like to take tablets ('we eat healthy foods already') and many avoid the sun because they are afraid of cancer. Vitamin D is not a commercially rewarding product and has no marketing industry. Although multivitamins are marketed and pushed by industry, they hardly contain the necessary amounts of vitamin D. The population in the Netherlands should be better informed on this issue and general practitioners need more tools in order to play a greater role in informing and advising their patients.


m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.
One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.


Anti-Nogo-A and training: can one plus one equal three?
Following spinal cord injury (SCI) the adult central nervous system (CNS) has a limited but substantial capacity for repair and plastic reorganisation. The degree of reorganisation is determined by a number of factors such as the extent and location of the lesion, the remaining circuit activity within the CNS and the age at injury. However, even in the best cases this spontaneous reorganisation does not lead to full recovery of the affected behaviour but instead often results in a functionally successful but compensatory strategy. Current SCI research focuses on enhancing fibre tract (re-)growth and recovery processes. Two currently promising approaches are the neutralisation of CNS growth inhibitory factors, and rehabilitative training of remaining networks. Independently, both approaches can lead to substantial functional recovery and anatomical reorganisation. In this review we focus on Nogo-A, a neurite growth inhibitory protein present in the adult CNS, and its role in regenerative and plastic growth following SCI. We then discuss the efforts of rehabilitative training and the potential combination of the two therapies.


Contribution of the inflammasome to inflammaging.
Inflammation is a natural part of the aging process. This process is referred to as inflammaging. Inflammaging has been associated with deleterious outcomes in the aging brain in diseases such as Alzheimer's disease and Parkinson's disease. The inflammasome is a multi-protein complex of the innate immune response involved in the activation of caspase-1 and the processing of the inflammatory cytokines interleukin (IL)-1β and IL-18. We have previously shown that the inflammasome plays a role in the aging process in the brain. In this study, we analyzed the brain of young (3 months old) and aged (18 months old) mice for the expression of inflammasome proteins. Our findings indicate that the inflammasome proteins NLRC4, caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and IL-18 are elevated in the cytosol of cortical lysates in aged mice when compared to young. In addition, in the cytosolic fraction of hippocampal lysates in aged mice, we found an increase in NLRC4, caspase-1, caspase-11, ASC and IL-1β. Moreover, we found higher levels of ASC in the mitochondrial fraction of aged mice when compared to young, consistent with higher levels of the substrate of pyroptosis gasdermin-D (GSDM-D) and increased pyroptosome formation (ASC oligomerization). Importantly, in this study we obtained fibroblasts from a subject that donated his cells at three different ages (49, 52 and 64 years old (y/o)) and found that the protein levels of caspase-1 and ASC were higher at 64 than at 52 y/o. In addition, the 52 y/o cells were more susceptible to oxidative stress as determined by lactose dehydrogenase (LDH) release levels. However, this response was ameliorated by inhibition of the inflammasome with Ac-Tyr-Val-Ala-Asp-Chloromethylketone (Ac-YVAD-CMK). In addition, we found that the protein levels of ASC and IL-18 are elevated in the serum of subjects over the age of 45 y/o when compared to younger subjects, and that ASC was higher in Caucasians than Blacks and Hispanics, whereas IL-18 was higher in Caucasians than in blacks, regardless of age. Taken together, our data indicate that the inflammasome contributes to inflammaging and that the inflammasome-mediated cell death mechanism of pyroptosis contributes to cell demise in the aging brain.


Evidence for dimer/tetramer equilibrium in Trypanosoma brucei 6-phosphogluconate dehydrogenase.
6-Phosphogluconate dehydrogenase (6PGDH), the third enzyme of the pentose phosphate pathway (PPP), is essential for biosyntheses and oxidative stress defence. It also has the function of depleting 6PG, whose accumulation induces cell senescence. 6PGDH is a proposed drug target for African trypanosomiasis caused by Trypanosoma brucei and for other microbial infections and cancer. Gel filtration, density gradient sedimentation, cross-linking and dynamic light scattering were used to assay the oligomerization state of T. brucei 6PGDH in the absence and presence of several ligands. The enzyme displays a dimer-tetramer equilibrium and NADPH (but not NADP) reduces the rate of approach to equilibrium, while 6PG is able to antagonize the NADPH effect. The different behaviour of the two forms of coenzyme appears to be related to the differences in ΔCp, with NADP binding ΔCp closer to what is expected of crystallographic structures, while NADPH ΔCp is three times larger. The estimated dimer-tetramer association constant is 1.5·10(6)M(-1), and the specific activity of the tetramer is about 3 fold higher than the specific activity of the dimer. Thus, cellular conditions promoting tetramer formation could allow an efficient clearing of 6PG. Experiments carried out on sheep liver 6PGDH indicate that tetramerization is a specificity of the parasite enzyme.


Gunshot casualties in Israel: A decade of violence.
The purpose of this study was to identify and characterize casualties hospitalized with assault (non-terror) related gunshot wounds (GSW) in Israel as a basis for determining the incidence, trends and at-risk population groups. This retrospective cohort study is based on data from the Israel National Trauma Registry. The data includes GSW casualties hospitalized between January 1, 2011 and December 31, 2020. Attempted suicide, unintentional injury, legal intervention, children (ages 0-9) and terror (Israeli-Arab conflict) related GSW were excluded. The remaining population was classified with an ICD-9-CM diagnosis code of 965.0-965.4. The study population included 2,763 GSW admissions. A noticeable increase in GSW casualties was reported, from 206 hospitalization in 2011 to 456 in 2020. The proportion of Arab casualties increased from 73.3% of all GSW casualties in 2011 to 90.8% in 2020, far more than their proportion in the population (∼20%). The majority of the GSW casualties were males (95.8%) and between the ages of 20 and 29 (42.2%). Among severe/critical casualties, 19% of Arabs and 9.9% of Jews arrived by private car. Severe thoracic and abdominal injuries were the prominent injuries among fatal casualties (47.6 and 40.8, respectively). While the all-severity mortality rate was 5.6% (n = 147), 24.4% (n = 135) of severe/critical (ISS16+) casualties died, with no significant differences between Jews and Arabs. Forty percent of deaths occurred in the emergency department. This study establishes that during the past decade in Israel, not only has there been a continuous increase in hospitalizations due to GSW, but also Arabs are at great risk of such related hospitalizations. Preventive strategies targeting at-risk groups are crucial for minimizing morbidity and mortality related to GSW in Israel.


Mutations in a steroid hormone-regulated gene disrupt the metamorphosis of the central nervous system in Drosophila.
The actions of steroid hormones on vertebrate and invertebrate nervous systems include alterations in neuronal architecture, regulation of neuronal differentiation, and programmed cell death. In particular, central nervous system (CNS) metamorphosis in insects requires a precise pattern of exposure to the steroid molting hormone 20-hydroxyecdysone (ecdysterone). To test whether the effects of steroid hormones on the insect nervous system are due to changes in patterns of gene expression, we examined Drosophila mutants of the ecdysterone-regulated locus, the Broad Complex (BR-C). This report documents aspects of CNS reorganization which are dependent on BR-C function. During wild-type metamorphosis, CNS components undergo dramatic morphogenetic movements relative to each other and to the body wall. These movements, in particular, the separation of the subesophageal ganglion from the thoracic ganglion, the positioning of the developing visual system, and the fusion of right and left brain hemispheres, are deranged in BR-C mutants. In addition, a subset of mutants shows disorganization of optic lobe neuropil, both within and among optic lobe ganglia. Optic lobe disorganization is found in mutants of the br and l(1)2Bc complementation groups, but not in those of the rbp complementation group. This suggests that the three complementation groups of this complex locus represent distinct but overlapping functions necessary for normal CNS reorganization. This study demonstrates that ecdysterone-regulated gene expression is essential for CNS metamorphosis, illustrating the utility of Drosophila as a model system for investigating the genetic basis of steroid hormone action on the nervous system.


Group I avian adenovirus and avian adeno-associated virus in turkey poults with inclusion body hepatitis.
Adenoviral inclusion body hepatitis (IBH) is rare in turkeys. Avian adenovirus group I and avian adeno-associated virus were isolated from the liver and pooled intestinal samples from 4-week-old turkey poults on two different ranches experiencing increased mortality. Grossly, a few birds from each ranch had a slightly enlarged liver with white foci of necrosis randomly scattered throughout. Microscopically, there was coagulative necrosis of hepatocytes with infiltration of a mixed population of inflammatory cells composed of lymphocytes, plasma cells, heterophils, and macrophages. In these livers, there were numerous basophilic intranuclear inclusion bodies in the hepatocytes. Transmission electron microscopy of the liver revealed 70 to 75 nm viral particles with icosahedral morphology consistent with adenovirus scattered throughout the nucleus of hepatocytes. All of the birds were serologically negative for haemorrhagic enteritis virus infection. Of some 5000 submissions over a 12-year period of turkey poults aged between 1 day and 10 weeks, only two single birds within two submissions had IBH.


Variation in the DNA methylation pattern of expressed and nonexpressed genes in chicken.
Using methyl-sensitive and -insensitive restriction enzymes, Hpa II and Msp I, the methylation status of various chicken genes was examined in different tissues and developmental stages. Tissue-specific differences in methylation were found for the delta-crystallin, beta-tubulin, G3PDH, rDNA, and actin genes but not for the histone genes. Developmental decreases in methylation were noted for the delta-crystallin and actin genes in chicken kidney between embryo and adult. Since most of the sequences examined were housekeeping genes, transcriptional differences are apparently not a necessary accompaniment to changes in DNA methylation at the CpG sites examined. The only exception is sperm DNA where the delta-crystallin, beta-tubulin, and actin genes are highly methylated and almost certainly not transcribed. However the G3PDH genes are no more highly methylated in sperm than in other somatic tissues. Many sequences homologous to the rDNA and histone probes used are unmethylated in all tissues examined including sperm, but a methylated rDNA subfraction is more heavily methylated in sperm than in other tissues. We speculate as to the significance of these differences in sperm DNA methylation in the light of possible requirements for early gene activation and the probable deleterious mutagenic effects of heavy methylation within coding sequences.


Limitations of carbon footprint as indicator of environmental sustainability.
Greenhouse gas accountings, commonly referred to with the popular term carbon footprints (CFP), are a widely used metric of climate change impacts and the main focus of many sustainability policies among companies and authorities. However, environmental sustainability concerns not just climate change but also other environmental problems, like chemical pollution or depletion of natural resources, and the focus on CFP brings the risk of problem shifting when reductions in CFP are obtained at the expense of increase in other environmental impacts. But how real is this risk? Here, we model and analyze the life cycle impacts from about 4000 different products, technologies, and services taken from several sectors, including energy generation, transportation, material production, infrastructure, and waste management. By investigating the correlations between the CFP and 13 other impact scores, we show that some environmental impacts, notably those related to emissions of toxic substances, often do not covary with climate change impacts. In such situations, carbon footprint is a poor representative of the environmental burden of products, and environmental management focused exclusively on CFP runs the risk of inadvertently shifting the problem to other environmental impacts when products are optimized to become more "green". These findings call for the use of more broadly encompassing tools to assess and manage environmental sustainability.


High-voltage cathode materials for lithium-ion batteries: freeze-dried LiMn0.8Fe0.1M0.1PO4/C (M = Fe, Co, Ni, Cu) nanocomposites.
Four LiMn0.8Fe0.1M0.1PO4/C (M = Fe, Co, Ni, Cu) cathode materials have been synthesized via a freeze-drying method. The samples have been characterized by powder X-ray diffraction, transmission electron microscopy, magnetic susceptibility, and electrochemical measurements. The composition and effective insertion of the transition-metal substituents in LiMnPO4 have been corroborated by elemental analysis, the evolution of the crystallographic parameters, and the magnetic properties. The morphological characterization of the composites has demonstrated that the phosphate nanoparticles are enclosed in a matrix of amorphous carbon. Among them, LiMn0.8Fe0.1Ni0.1PO4/C is the most promising cathode material, providing a good electrochemical performance in all aspects: high voltage and specific capacity values, excellent cyclability, and good rate capability. This result has been attributed to several factors, such as the suitable morphology of the sample, the good connection afforded by the in situ generated carbon, and the amelioration of the structural stress provided by the presence of Ni(2+) and Fe(2+) in the olivine structure.


Association between umbilical blood gas parameters and neonatal morbidity and death in neonates with pathologic fetal acidemia.
Our purpose was to correlate umbilical artery blood gas parameters with neonatal death and indicators of morbidity in neonates with pathologic fetal acidemia (pH <7.0). We reviewed maternal and neonatal charts of 93 neonates with an umbilical artery pH <7.0 who were delivered at 2 university-based centers. The relationships between umbilical artery pH, PO (2), PCO (2), bicarbonate, base deficit, and neonatal variables-death, need for intubation, cardiopulmonary resuscitation, seizures, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage, meconium, sepsis, and intrauterine growth restriction-were determined with the Student t test, Mann-Whitney U test, and multiple logistic regression analysis. Data are presented as either median with 25th-75th percentiles or mean +/- SD. The mean gestational age at delivery was 37.9 +/- 3. 6 weeks, and the mean birth weight was 3003 +/- 866 g. There was no relationship between neonatal death, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, patent ductus arteriosus, meconium, sepsis, and any umbilical artery blood gas parameter. The PO (2) was not related to any of the variables studied. A lower umbilical artery pH was associated with hypoxic-ischemic encephalopathy (6.69 vs 6.93, P =.03), cardiopulmonary resuscitation (6.83 vs 6.93, P =.03), seizure (6.75 vs 6.93, P =.02), intubation (6.83 vs 6.94, P <.001), and intrauterine growth restriction (6.72 vs 6.93, P =.01). Greater mean base deficit was associated with seizure (20.6 vs 15, P =.01), intubation (18.0 vs 13.7, P <.001), cardiopulmonary resuscitation (18.5 vs 15.0, P =.03), intrauterine growth restriction (22.0 vs 14. 0, P =.02), and hypoxic-ischemic encephalopathy (24.0 vs 14.5, P =. 03). Arterial PCO (2) was higher only in infants with hypoxic-ischemic encephalopathy (138 vs 95.5, P =.048), intubation (106.0 vs 90.5, P =.003), and cardiopulmonary resuscitation (106.5 vs 93.0, P =.04). After control for birth weight and gestational age in the multivariate analysis, base deficit and bicarbonate were independently related to death or morbidity. Our data suggest that "pathologic" fetal acidemia is indicated by an umbilical artery pH <7.00 with a metabolic component. The metabolic component of fetal acidemia (ie, base deficit and bicarbonate) is the most important variable in subsequent neonatal morbidity. As expected, the umbilical artery PO (2) has no apparent clinical utility. The ability to predict more accurately which newborn infants with fetal acidemia are at risk of having complications may lead to a more efficient implementation of preventive measures.


Interleukin-8 release from human neutrophils after phagocytosis of Listeria monocytogenes and Yersinia enterocolitica.
The release of interleukin-8 (IL-8) from human neutrophils was investigated after their internalisation of the invasive bacteria Listeria monocytogenes and Yersinia enterocolitica. Three pairs of bacterial strains were used to study the influence of listeriolysin O, invasiveness and Yersinia virulence plasmid (pYV)-encoded proteins on neutrophil cytokine synthesis. The neutrophils secreted IL-8 into the culture supernate after exposure to all strains tested. With L. monocytogenes, the virulence factor listeriolysin O had no effect on IL-8 secretion, whereas a non-invasive mutant induced greater IL-8 release than the corresponding invasive strain. With Y. enterocolitica, expression of virulence plasmid-encoded proteins appeared to be responsible for diminished IL-8 release. Northern blot analysis showed that the induced IL-8 release was always accompanied by an enhanced level of cytoplasmic IL-8 mRNA. Cytokine priming of neutrophils with granulocyte macrophage colony-stimulating growth factor (GM-CSF), unlike granulocyte colony-stimulating factor (G-CSF), led to further enhancement of IL-8 secretion induced after internalisation of the bacteria. Again, the increased IL-8 release, from GM-CSF primed neutrophils, was accompanied by an increased level of cytoplasmic IL-8 mRNA. The results emphasise the role of IL-8 in neutrophil-mediated host defence mechanisms during the acute phase of L. monocytogenes and Y. enterocolitica infection.


Performance degradation of a Michelson interferometer due to random sampling errors.
The performance of a standard Michelson interferometer is degraded by disturbances that cause the interferogram signal to be sampled at nonconstant time intervals. A formula that shows how the power spectrum of the random disturbances interacts with the signal to contaminate different regions of the measured spectrum is derived for the spectral noise. The sampling noise does not look conventionally noiselike because it is correlated over large regions of the measured spectrum, and adjustment of the unbalanced background interferogram to match the size of the balanced background interferogram minimizes the sampling-noise amplitude.


A practical guide to genetic testing in endocrinology.
Rapid advances in sequencing technology have led to significant improvements in genomic analysis, resulting in increased understanding of the molecular basis of many endocrine conditions. Genomic testing for rare disease is being integrated into everyday clinical practice, as the importance of confirming a genetic diagnosis earlier in a patient's pathway helps direct their clinical care and specialized management. In England, the new nationally commissioned Genomic Medicine Service has started to deliver testing for rare and inherited disease and cancer somatic tissue via seven Genomic Laboratory Hubs. The range of genetic tests, technology employed and eligibility criteria for patient testing are all defined in the National Genomic Test Directory. This review provides practical guidance on how to access genomic testing for endocrine disease, how to interpret and relay results, and details how genetic counselling can help integrate results into ongoing care of the individual and their family. This article discusses general principles as well as specifics related to the process of genomic testing in England. We illustrate mainstream genetic testing with a clinical scenario involving an individual with inherited endocrine neoplasia, followed by a generic description of the different steps involved, including informed consent to proceed to diagnostic testing. Most genetic tests analyse multiple genes simultaneously by next-generation sequencing, and variant interpretation may yield not only pathogenic explanatory results, but also ambiguous outcomes, with variants of unknown significance or incidental findings. Delivery of results and posttest genetic counselling are therefore key components of integrating genetic testing into routine endocrine care.


Prescribing practices and attitudes toward giving children antibiotics.
To investigate whether overprescribing is common in treatment of pediatric upper respiratory infections and to examine factors that influence prescribing antibiotics for children. A random, stratified sample of practising family physicians was surveyed with a mailed questionnaire. Initial nonresponders were mailed a second questionnaire. British Columbia. A total of 608 general and family physicians. Response rate was 64%; 392/612 surveys were completed. Physicians' self-reported prescribing practices and knowledge of and attitudes toward using antibiotics for children's upper respiratory tract infections. Relative to treatment guidelines developed for the study, most physicians responded appropriately to the cough (94%) and lobar pneumonia (99.1%) vignettes. More than half the physicians (56.5%) reported they would immediately prescribe antibiotics for tympanic membrane dysfunction, and 79.4% indicated they would prescribe antibiotics for pharyngitis without obtaining a laboratory culture. Approximately 25% of physicians in the study did not believe that prior antibiotic use increased personal risk for acquiring drug-resistant infection, and 23.1% did not believe that antibiotic use was an important factor in promoting resistance in their communities. Education in current treatment of pediatric upper respiratory tract illnesses and antimicrobial drug resistance is required. The high response to the questionnaire (64%) and the many requests from physicians to receive the project's educational materials (45%) indicate a high level of interest in this subject.


Gene loss and parallel evolution contribute to species difference in flower color.
Although the importance of regulatory and functional sequence evolution in generating species differences has been studied to some extent, much less is known about the role of other types of genomic changes, such as fluctuation in gene copy number. Here, we apply analyses of gene function and expression of anthocyanin pigment pathway genes, as well as cosegregation analyses in backcross populations, to examine the genetic changes involved in the shift from blue to red flowers in Andean Iochroma (Solanaceae). We demonstrate that deletion of a gene coding for an anthocyanin pathway enzyme was necessary for the transition to red floral pigmentation. The downregulation of a second pathway gene was also necessary for the novel flower color, and this regulatory pattern parallels the genetic change in the two other red-flowered species in the sister family Convolvulaceae in which flower color change has been examined genetically. Finally, we document a shift in enzymatic function at a third locus, but the importance of this change in the transition to red flowers depends on the exact order with which the three changes occurred. This study shows that gene inactivation or loss can be involved in the origin of phenotypic differences between species, thereby restricting the possibility of reversion to the ancestral state. It also demonstrates that parallel evolution of red flowers in three different species occurs via a common developmental/regulatory change but by mutations in different genes.


Decision making in migraine patients taking sumatriptan: an exploratory study.
Until recently, much of the medical and psychological literature has examined and conceptualized the taking of medication from the viewpoint of adherence to or compliance with recommendations from health professionals. However, some authors have argued that medication taking is mostly determined by patient decision making. In order to investigate the factors and processes influencing the patient's decision to take or not take abortive therapy for migraines, 20 migraineurs (according to International Headache Society criteria) were asked, using a semistandardized interview, what factors influenced their decision to take or not take sumatriptan when they had a migraine. Qualitative analysis revealed a 2-stage decision-making process. First, the patient collects information from interoceptive and environmental cues (symptom monitoring) to predict whether the headache that is beginning will become a migraine. Then, if the patient decides it is a migraine, he or she weighs various factors to decide whether to take sumatriptan. These results are consistent with the current cognitive psychology literature on decision-making processes and could lead to significant improvements in understanding the process by which patients make decisions about taking sumatriptan and, ultimately, could lead to better patient education and more effective headache control. They also open a whole new field in the empirical investigation of medication-taking behavior.


Two-Step Electrochemical Au Nanoparticle Formation in Polyaniline.
In this work, we use a two-step cyclic electrochemical process to insert Au into polyaniline (PANI). It was suggested previously that this method would lead to the formation of atomic Au clusters with controlleds number of Au atoms without providing morphological proof. In each cycle, tetrachloroaurate anions (AuCl4-) are attached on the protonated imine sites of PANI, followed by a controlled reduction using cyclic voltammetry (CV). In contrast to previous work, we demonstrate that the reduction leads to the nucleation and growth of an Au nanoparticle (NP) whose density and size dispersion depend on the Au loading in PANI. Adding more deposition cycles increases the Au NP density and size. Transmission electron microscopy (TEM) and corresponding energy dispersive X-ray spectroscopy (EDS) indicate a homogeneous distribution of Au elements in the PANI matrix before CV reduction, while Au elements are aggregated and clearly localized in the NPs positions after CV reduction. We further use Rutherford backscattering spectrometry (RBS) to quantify the Au uptake in PANI. The Au distribution is verified to be initially homogeneous across the PANI layer whereas the increasing number of deposition cycles leads to a surface segregation of Au. We propose a two-step growth model based on our experimental results. Finally, we discuss the results with respect to the formation of atomic Au clusters reported previously using the same deposition method.


Transition from open to laparoscopic adrenalectomy: the need for advanced training.
We sought to determine the learning curve for laparoscopic adrenalectomy (LA), current use of the procedure, and if indications for adrenalectomy had changed in the past decade. A retrospective chart review was performed for all adrenalectomies after 1990. Practicing community surgeons in Oregon were mailed a questionnaire. Seventy-five LAs were performed at the Oregon Health and Sciences University and Portland VA Medical Center. Average operating room (OR) time was 161 min and average estimated blood loss (EBL) was 84 ml. There were four complications and two conversions. Comparing the first 20 to the last 20 patients, OR times were 154 vs 159 min (not significant), and EBL was 102 vs 47 ml ( p < 0.05). There were two vs one complications ( p > 0.05) and one conversion each. Most residents completed less than two procedures during training, and community surgeons performed none during training. Of 17 currently performing LA, 14 had postresidency training. Open technique was used more often for hormonal ablation and malignancy. Operative time and complications do not decrease with experience, but EBL does. Few, if any, residents acquire enough experience to perform LA in practice. The procedure is performed laparoscopically more often for benign disease.


Systems map of interventions to improve dietary intake of pre-school aged children: A scoping review.
Implementation and sustaining impact of early childhood nutrition interventions in practice remains a challenge. An understanding of the extent to which determinants across multiple levels of the food system are being addressed may improve success. This literature review aimed to synthesise the evidence on interventions targeting dietary intake and eating behaviours in preschool children using a systems approach. Eligible studies included intervention studies targeting the dietary intake of preschool children aged 2-5 years in high income countries, published in English after January 2000. Interventions were categorised to the Determinants of Nutrition and Eating (DONE) framework for children developed and evaluated by experts across multiple fields. The framework maps and ranks 411 factors driving eating behaviours and nutrition and can be used to systematically summarise determinants. DONE ranks each determinant for its perceived research priority. A total of 160 eligible studies were identified. Most interventions targeted interpersonal (n = 101, 63.1%) and individual (n = 85, 53.1%) level determinants, with fewer targeting environmental (n = 55, 34.4%) and policy level (n = 17, 10.6%) determinants. The most frequently addressed determinants were Parental Resources and Risk Factors (n = 85) and Children's Food Knowledge, Skills and Abilities (n = 67). These determinants had a Moderate research priority rating. Home Food Availability and Accessibility at the environmental level is classified as the highest research priority, however, only 15 of 160 interventions addressed this determinant. This review highlights home food availability and accessibility as potential leverage points for future interventions to improve children's dietary intake and eating behaviours.


[Stenosis complications in digestive surgery: a histomorphological contribution. Comparison of mechanical and manual sutures].
Surgeons variously estimate usage of mechanical staplers in digestive surgery especially about the increase of the incidence of late complications like stricture (as some authors refer). We report a histomorphological aid to the comparison of staplers and hand-sewn sutures. Our aim was to observe at long term the healing process in the sutured tissue in the canine gastro-enteric tract. We describe three histological pieces: one manual suture in a dog which was euthanatized and necropsied 5 months after operation and two mechanical sutures performed in two different dogs: one died because of a gastric torsion 18 months after the operation while the other was euthanatized 5 months after the operation. The histomorphological study has been carried out with a peculiar cutting (Exact) and including method which lets the staples in situ. Compared analysis showed that cicatrization goes on better in stapled than in hand sutured tissue.


Treatment of mice with a herbal preparation (Liv. 52) reduces the frequency of radiation-induced chromosome damage in bone marrow.
Induction of chromosomal aberrations was studied from 1/4 to 14 days post irradiation in the bone marrow of mice treated or not with Liv. 52, a herbal preparation, prior to 4.5 Gy exposure. The frequency of chromatid and chromosomal aberrations started increasing at day 1/4 in the irradiation and Liv. 52 + irradiated groups. The highest frequency of aberrations was recorded at day 1/2 post exposure which declined after day 1 in both groups. The frequency of both types of aberrations was significantly lower in the Liv. 52 + irradiated group than in the irradiated group.


Burden of Comorbidities in Hospitalizations for Cannabis Use-associated Intractable Vomiting during Post-legalization Period.
Objective The aim of this study was to observe the trends of intractable vomiting and cannabis use disorder (CUD) with demographic characteristics, medical and psychiatric comorbidities, and hospitalization outcomes. Methods We conducted a retrospective cohort study using the nationwide inpatient sample (2010 to 2014). Patients aged 16-50 years discharged with a primary diagnosis of intractable vomiting and CUD were included (N = 9,601). We used the linear-by-linear association chi-square test and independent-sample T-test for measuring the categorical and continuous data, respectively. Results The number of intractable vomiting hospitalizations with CUD had an increasing trend (P < 0.001) with a 28.6% increase over five years. About half of the study population included young (16-30 years, 48.4%) males (57.2%). There was a decreasing trend (P = 0.041) in the prevalence of intractable vomiting with CUD in non-Hispanic Whites and Blacks, whereas there was 778% increase in Hispanics. The mean length of stay was 3.2 days which had a decreasing linear trend, and total hospital charges showed an increasing trend (P < 0.001), averaging $22,890. Electrolyte disorders (55.3%), hypertension (25.3%), chronic lung disease (11.9%), and deficiency anemia (10.3%) constituted the majority of comorbidities, with anemia showing a statistically significant increasing trend (P = 0.004). Anxiety disorders increased from 20.8% to 30.8% over five years, whereas depression decreased from 19.2% to 16.4% (P < 0.001). Concomitant tobacco abuse/dependence was present in 41.2% of patients with CUD. Conclusion The results of our study show that the intractable vomiting hospitalizations related to CUD have increased significantly over a five-year period. The general public and healthcare practitioners should be made aware of the paradoxical gastrointestinal side effects of cannabis.


Pregnant adolescents' perspectives of pregnancy.
To gain a clearer understanding of teens' perspectives on pregnancy and parenting. DESIGN Descriptive qualitative study using grounded theory. The sample was comprised of 20 pregnant 15- to 19-year-old teens in the second or third trimester of pregnancy who planned to keep their child. A taped interview of each participant was performed either in the school the teen was attending or in the privacy of her home. Data were analyzed using the constant comparative method. Interviews were compared with each other to confirm/disconfirm emerging themes. The comparison of the data from the 20 interviews resulted in themes clearly describing the teens' perceptions of the changes related to pregnancy, how they managed these changes, and their views on mothering. Three major themes emerged: "The pregnant me--unexpected changes," "Transformed relationships," and "Envisioning mothering." Nurses caring for pregnant adolescents who have made the decision to keep their babies should carefully assess each individual's strengths, weaknesses, hopes, and goals prior to developing a plan of care. Identifying the teens' living situations and support from family, father of the baby, and/or friends and recognizing and building upon the strengths the teens bring to the pregnancy may influence the pregnancy's outcome. Encouraging attendance and participation in programs specifically designed for pregnant adolescents and adolescent parents may be a helpful strategy for these teens.


Oral D-penicillamine for the prevention of retinopathy of prematurity in very low birth weight infants: a randomized, placebo-controlled trial.
To compare prophylactic enteral D-penicillamine (DPA) with placebo for prevention of 'retinopathy of prematurity (ROP) or death' among very low birth weight (VLBW) infants. This was a double-blind, single-centre, randomized, placebo-controlled trial with stratification (for birth weight <1250 and ≥1250 g) and blocking. Inborn neonates with birth weight 750-1500 g, gestation ≤32 weeks, age ≤5 days, who tolerated feeds were eligible. Neonates with gastro-intestinal malformations, life-threatening malformations and necrotizing enterocolitis were excluded. Enrolled subjects were randomly allocated to receive oral DPA suspension at 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg/day for another 11 days or placebo. The primary outcome was 'any ROP or death'. Secondary outcomes included any ROP, treatable ROP, adverse effects and feed intolerance. A total of 88 subjects were enrolled. Baseline characteristics were similar with the exception of multiple gestation. There were no significant differences in primary and secondary outcomes, even after adjusting for multiple gestation and on sub-group analysis. No adverse reaction was noted. Prophylactic enterally administered DPA suspension in a dose 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg once per day for next 11 days, does not prevent 'any stage ROP or death' or 'ROP requiring treatment' in VLBW infants. DPA is well tolerated and does not have any major short-term adverse effects.


The Impact of the Lubricant Dose on the Reduction of Wear Dies Used in the Forging Process of the Valve Forging.
The paper presents the results of research on the influence of the settings of lubrication and cooling system parameters (solenoid valve opening time and lubricant feed pressure in terms of its quantity) in order to select the optimal lubricating conditions and thus reduce the wear of the dies used in the first forging operation of the valve forging made of high-nickel steel. Based on the observation of lubrication in the industrial process, it was found that a significant part of the lubricant fails to reach the die cavity, reaching the outside of it, which causes die wear due to seizure resulting from adhesion of the forging material to the tool surface as well as high lubricant consumption and dirt in the press chamber. The authors proposed their own mobile lubricating and cooling system, which allows for a wide range of adjustments and provided with automatic cleaning procedures of the entire system, unlike the fixed lubrication system used so far in the industrial process. First, tests were carried out in laboratory conditions to determine the highest wettability and the lubricant remaining inside the tool cavity. These tests determined the lubrication system parameter settings that ensured that the greatest amount of lubricant remains in the cold die cavity without the forging process. Then, to verify the obtained results, tests were carried out in the industrial process of hot die forging of valve forgings for short production runs of up to 500 forgings. The results were compared with the measurement of changes in the geometry of tools and forgings based on 3D scanning and surface topography analysis with the use of SEM (Scanning Electron Microscope). For the best results (the variant of the setting of the dose and the time of exposure to lubricant), the forging process was carried out with the use of a new tool up to the maximum service life.


[Effect of complete basal undercutting of the septum on the activity of its neurons].
Spontaneous and evoked by sensory stimuli neuronal activity of medial and lateral septal nuclei deprived of basal connections, was investigated in chronic unanaesthetized rabbits. After basal undercutting of septum many neurones in both nuclei produced highly regular "pacemaker-like" activity. The proportion of neurones with rhythmic bursts of spontaneous activity did not change, but the frequency of bursts decreased to 2.8--3.9 per second. Reactivity of neurones to sensory stimuli was low in both nuclei. Electric stimulation of the hippocampus was highly effective. The majority of septal neurones responded to each stimulus by a short (30--150 msec) inhibition. The problems in connection with possible organization of rhythmic theta-activity of septal neurones are discussed.


Gastrointestinal tract ulcers in pediatric intestinal transplantation patients: etiology and management.
One of the observed complications in patients after intestinal transplantation is the occurrence of ulcers in the native or transplanted gastrointestinal tract. Previous reports have described the appearance of ulcers but have not described any systemic approach to accurately diagnose the etiology of the ulcer. We evaluated 112 intestinal transplantation patients at our institution, in which endoscopic examination identified ulcer formation in 11 patients. No common or defining demographic or clinical variables were found in the patients with ulcers. Biopsies were obtained from the ulcer edge as well as the intervening mucosa. The most common changes in the ulcers were compatible with post-transplant lymphoproliferative disorder (PTLD), acute rejection, and viral infections. These changes could occur simultaneously and retrospective analysis showed that ulcers could have concomitant etiologies. Endoscopically directed biopsies of ulcer edges often displayed morphologic changes compatible with acute rejection of the graft. Some patients were treated for rejection based on the changes within the mucosa outside the ulcer bed, and they responded with resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and reinforce the concept that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa.


Relationship between Agronomic Parameters, Phenolic Composition of Grape Skin, and Texture Properties of Vitis vinifera L. cv. Tempranillo.
The relationship between the agronomic parameters of grapevine and the phenolic composition of skin of Vitis vinifera L. cv. Tempranillo grapes was assessed. The physical and mechanical properties of berries and their skins were also determined and correlated to the chemical composition. Results showed a significant negative correlation between grapevine vigor-related parameters (such as leaf area and bunch weight) and anthocyanin composition, whereas the percentage (w/w) of seeds was negatively correlated with the amount of flavanols of grape skins. Texture properties of grape skins also showed an important relationship with chemical composition. Berry hardness showed a negative correlation with the coumaroyl-anthocyanin derivatives, but it was positively correlated to skin flavanic composition. Moreover, significant regressions with high coefficients of determination were found between phenolic composition and grapevine vigor-related and texture variables, thus pointing out that these parameters might be useful for estimating the phenolic composition of grape skins.


Monooxygenase, a novel beta-cypermethrin degrading enzyme from Streptomyces sp.
The widely used insecticide beta-cypermethrin has become a public concern because of its environmental contamination and toxic effects on mammals. In this study, a novel beta-cypermethrin degrading enzyme designated as CMO was purified to apparent homogeneity from a Streptomyces sp. isolate capable of utilizing beta-cypermethrin as a growth substrate. The native enzyme showed a monomeric structure with a molecular mass of 41 kDa and pI of 5.4. The enzyme exhibited the maximal activity at pH 7.5 and 30°C. It was fairly stable in the pH range from 6.5-8.5 and at temperatures below 10°C. The enzyme activity was significantly stimulated by Fe(2+), but strongly inhibited by Ag(+), Al(3+), and Cu(2+). The enzyme catalyzed the degradation of beta-cypermethrin to form five products via hydroxylation and diaryl cleavage. A novel beta-cypermethrin detoxification pathway was proposed based on analysis of these products. The purified enzyme was identified as a monooxygenase by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and N-terminal protein sequencing. Given that all the characterized pyrethroid-degrading enzymes are the members of hydrolase family, CMO represents the first pyrethroid-degrading monooxygenase identified from environmental microorganisms. Taken together, our findings depict a novel pyrethroid degradation mechanism and indicate that the purified enzyme may be a promising candidate for detoxification of beta-cypermethrin and environmental protection.


A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile.
Uveal (ocular) melanoma is an aggressive cancer that metastasizes in up to half of patients. Uveal melanoma spreads preferentially to the liver, and the metastatic disease is almost always fatal. There are no effective therapies for advanced metastatic disease, so the most promising strategy for improving survival is to detect metastasis at an earlier stage or to treat high-risk patients in an adjuvant setting. An accurate test for identifying high-risk patients would allow for such personalized management as well as for stratification of high-risk patients into clinical trials of adjuvant therapy.We developed a gene expression profile (GEP) that distinguishes between primary uveal melanomas that have a low metastatic risk (class 1 tumors) and those with a high metastatic risk (class 2 tumors). We migrated the GEP from a high-density microarray platform to a 15-gene, qPCR-based assay that is now performed in a College of American Pathologists (CAP)-accredited Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory on a routine clinical basis on very small samples obtained by fine needle aspiration and on archival formalin-fixed specimens. We collaborated with several centers to show that our specimen collection protocol was easily learned and performed and that it allowed samples to be safely and reliably transported from distant locations with a very low failure rate. Finally, we showed in a multicenter, prospective study that our GEP assay is highly accurate for predicting which patients will develop metastatic disease, and it was significantly superior to the previous gold standard, chromosome 3 testing for monosomy 3. This is the only prognostic test in uveal melanoma ever to undergo such extensive validation, and it is currently being used in a commercial format under the trade name DecisionDx-UM in over 100 centers in the USA and Canada.


[Modification of performance by activation in the elderly].
The effects of activation on performance are rarely investigated in older people. An experiment on the effects of psychic activation on free recall of word lists is reported. Participants were healthy women (N = 71) of two age groups (60-69 versus 70-79 years). Psychic activation was induced by intermittent white noise of three intensities (55, 80, 90 dBA). The effects were assessed by self-report inventories concerning mood and performance, by vegetative variables, and by memory tests. The memory tests consisted of free recall tasks under instructions of power and speed. Under the power condition memory performance decreased with activation in both age groups. Free recall performance under speed conditions resulted in inverted U-shaped relations between activation and performance only for the younger sample; the older group was not affected. To explain the results possible mediators are discussed.


Paediatric dosing errors before and after electronic prescribing.
To compare the incidence and severity rating of dose prescribing errors before and after the implementation of a commercially available electronic prescribing system at a tertiary care children's hospital. Dose errors were identified using prescription review to detect errors. Severity rating was determined by five judges using a validated, reliable scoring tool. The mean score for each error was used as an index of severity. Dose prescribing errors occurred in 88 of the 3939 (2.2%) items prescribed for outpatients and inpatients, and on discharge prescriptions prior to the implementation of electronic prescribing (EP). After EP, there were 57 dose errors in 4784 (1.2%) items prescribed (1% absolute reduction (p<0.001 chi(2) test; 95% CI of difference in proportions -1.6% to -0.5%)). A decrease in the severity rating of dose errors was also seen: dose errors with potentially minor outcomes 35/3939 (0.89%) pre vs 21/4784 (0.44%) post (95% CI of difference in proportions -0.8% to -0.11%, p=0.009 chi(2) test); moderate outcome 46/3939 (1.17%) pre vs 33/4784 (0.69%) post (95% CI of difference in proportions -0.91% to -0.08, p=0.019, chi(2) test); severe outcome: 7/3939 (0.18%) pre vs 3/4784 (0.06%) post (95% CI of difference in proportions -0.31% to +0.04, p=0.11, chi(2) test). Electronic prescribing appears to reduce rates of dosing errors in paediatrics, but larger studies are required to assess the effect on the severity of these errors and in different settings.


Pheromonal and reproductive function of F prostaglandins and their metabolites in teleost fish.
Although the function of prostaglandins in fish reproduction has not been well studied, it is becoming increasingly clear that prostaglandin F2 alpha or a compound closely resembling it serves three critical roles mediating reproductive activities in teleost fish. First, it appears to play a paracrine role in the ovary stimulating and/or modulating follicular rupture. Second, circulating levels of F prostaglandins rise at the time of ovulation and travel to the brain where they elicit female sexual behavior. Third, recent studies indicate that F prostaglandin is metabolized and released to the water where it functions as a sex pheromone stimulating male sexual behavior. Although these roles have been best characterized in the goldfish, ongoing studies indicate that metabolites of prostaglandin F2 alpha may commonly function as pheromones in many fish. Many questions remain about the identity(ies), origins, and species-specificity of the prostaglandin pheromone.


Acinetobacter baumannii coordinates central metabolism, plasmid dissemination, and virulence by sensing nutrient availability.
Plasmid conjugation plays an important role in the dissemination of antibiotic-resistance genes. The emergence of multidrug-resistant isolates of Acinetobacter baumannii poses grave challenges in treating infections caused by this notorious nosocomial pathogen. Yet, the composition, functionality, and regulation of conjugative machinery utilized by A. baumannii remain poorly understood. Here, we found that conjugation of the major plasmid pAB3 of A. baumannii is mediated by a type IVB secretion system similar to the Dot/Icm transporter of Legionella pneumophila. Furthermore, the expression of the structural genes of the Dot/Icm-like system is co-regulated with genes involved in central metabolism by the GacS/GacA two-component system in response to various metabolites, including intermediates of the tricarboxylic acid cycle. Loss of GacS/A also severely impaired bacterial virulence. These results establish that A. baumannii coordinates metabolism with plasmid conjugation and virulence by sensing nutrient availability, which may be exploited to develop inhibitory agents for controlling the spread of drug-resistance genes and virulence factors. IMPORTANCE Plasmid conjugation is known to be an energy-expensive process, but our understanding of the molecular linkage between conjugation and metabolism is limited. Our finding reveals that Acinetobacter baumannii utilizes a two-component system to co-regulate metabolism, plasmid transfer, and virulence by sensing reaction intermediates of key metabolic pathways, which suggests that nutrient availability dictates not only bacterial proliferation but also horizontal gene transfer. The identification of Dot/Icm-like proteins as components of a conjugation system involved in the dissemination of antibiotic-resistance genes by A. baumannii has provided important targets for the development of agents capable of inhibiting virulence and the spread of anti-microbial-resistance genes in bacterial communities.


Aged rats have an altered immune response and worse outcomes after traumatic brain injury.
Initial studies suggest that increased age is associated with worse outcomes after traumatic brain injury (TBI), though the pathophysiological mechanisms responsible for this remain unclear. Immunosenescence (i.e., dysregulation of the immune system due to aging) may play a significant role in influencing TBI outcomes. This study therefore examined neurological outcomes and immune response in young-adult (i.e., 10 weeks old) compared to middle-aged (i.e., 1 year old) rats following a TBI (i.e., fluid percussion) or sham-injury. Rats were euthanized at either 24 h or one-week post-injury to analyze immune cell populations in the brain and periphery via flow cytometry, as well as telomere length (i.e., a biomarker of neurological health). Behavioral testing, as well as volumetric and diffusion-weighted MRI, were also performed in the one-week recovery rats to assess for functional deficits and brain damage. Middle-aged rats had worse sensorimotor deficits and shorter telomeres after TBI compared to young rats. Both aging and TBI independently worsened cognitive function and cortical volume. These changes occurred in the presence of fewer total leukocytes, fewer infiltrating myeloid cells, and fewer microglia in the brains of middle-aged TBI rats compared to young rats. These findings indicate that middle-aged rats have worse sensorimotor deficits and shorter telomeres after TBI than young rats, and this may be related to an altered neuroimmune response. Although further studies are required, these findings have important implications for understanding the pathophysiology and optimal treatment strategies in TBI patients across the life span.


An interface-directed coassembly approach to synthesize uniform large-pore mesoporous silica spheres.
A facile and controllable interface-directed coassembly (IDCA) approach is developed for the first time to synthesize uniform discrete mesoporous silica particles with a large pore size (ca. 8 nm) by using 3-dimensional macroporous carbon (3DOMC) as the nanoreactor for the confined coassembly of template molecules and silica source. By controlling the amount of the precursor solution and using Pluronic templates with different compositions, we can synthesize mesoporous silica particles with diverse morphologies (spheres, hollow spheres, and hemispheres) and different mesostructure (e.g., 2-D hexagonal and 3D face centered cubic symmetry), high surface area of about 790 m(2)/g, and large pore volume (0.98 cm(3)/g). The particle size can be tunable from submicrometer to micrometer regimes by changing the macropore diameter of 3DOMC. Importantly, this synthesis concept can be extended to fabricate multifunctional mesoporous composite spheres with a magnetic core and a mesoporous silica shell, large saturated magnetization (23.5 emu/g), and high surface area (280 m(2)/g). With the use of the magnetic mesoporous silica spheres as a magnetically recyclable absorbent, a fast and efficient removal of microcystin from water is achieved, and they can be recycled for 10 times without a significant decrease of removal efficiency for microcystin.


Anaesthetic considerations in Klippel-Feil syndrome.
Anaesthesia for the repair of a large occipito cervical encephalomyelocele in a neonate with Kippel-Feil syndrome is described. The fusion of the cervical spines, a short neck, low posterior hair line and Sprengel's deformity, which were present in this patient, collectively indicated Klippel-Feil syndrome. In addition to the usual stigmata of the syndrome, this patient had a large encephalomyelocele and persistent patent ductus arteriosus complicated by congestive heart failure. Patients with this syndrome are vulnerable to cervical spinal cord injury and are at high risk for neurological injury not only during laryngoscopy and intubation but thereafter. Implications of Kippel-Feil syndrome for the anaesthetist are reviewed and discussed.


Skin optics.
Quantitative dosimetry in the treatment of skin disorders with (laser) light requires information on propagation of light in the skin related to the optical properties of the individual skin layers. This involves the solution of the integro-differential equation of radiative transfer in a model representing skin geometry, as well as experimental methods to determine the optical properties of each skin layer. These activities are unified under the name skin optics. This paper first reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Then, previously published data as well as some current unpublished data on (human) stratum corneum, epidermis and dermis, have been collected and/or (re)analyzed in terms of absorption coefficient, scattering coefficient, and anisotropy factor of scattering. The results are that the individual skin layers show strongly forward scattering (anisotropy factors between 0.7 and 0.9). The absorption and scattering data show that for all wavelengths considered scattering is much more important than absorption. Under such circumstances, solutions to the transport equation for a multilayer skin model and finite beam laser irradiation are currently not yet available. Hence, any quantitative dosimetry for skin treated with (laser) light is currently lacking.


Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.


A cross-sectional study of Salmonella in pre-slaughter pigs in a production compartment of northern Thailand.
A cross-sectional study was conducted to determine the prevalence of Salmonella and to associate management factors in fattening pigs in a production compartment of northern Thailand. A total of 194 fecal samples and 166 environmental samples were collected from 22 fattening pig herds for isolation and identification of Salmonella. An additional 427 serum samples were collected from the same herds to determine Salmonella antibodies using ELISA. A questionnaire was used to collect management factors likely to be associated with Salmonella identification. Prevalence of Salmonella in each sample and its confidence interval was adjusted for clustering by herds using linearization technique. A generalized estimating equation was used to determine the odds ratio and significance level for each management factor in a logistic regression model. Salmonella was found in all 22 study pig herds with a fecal sample prevalence of 63% (95%CI: 56-69%) and a serum sample prevalence of 72%. However, isolation results were not significantly different from ELISA results. The most isolated serotype was Salmonella Rissen (49%) followed by Salmonella Typhimurium (19%), Salmonella Stanley (12%) and Salmonella Weltevreden (4%) being significantly different in the different specimens collected (p=.024). The final logistic regression model with isolation results as outcome showed that medium herd size (OR=2.32, p=0.003), quality certification according to the Department of Livestock Development standard (OR=1.88, p=0.000), use of effective microorganisms (OR=1.51, p=0.022), slurry waste management (OR=2.17, p=0.000) and less number of pigs per pen (OR=1.12, p=0.000) were significantly associated with positive Salmonella isolation; with positive ELISA results, however, only the use of effective microorganisms was significantly associated (OR=2.63, p=0.011).


One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study.
Adherence to anti-osteoporosis medications is poor. We carried out a cohort study using a real-world population database to estimate the persistence of anti-osteoporosis drugs. Unadjusted 2-year persistence ranged from 10.3 to 45.4%. Denosumab users had a 40% lower risk of discontinuation at 2 years compared to alendronate users. The purpose of this study was to estimate real-world persistence amongst incident users of anti-osteoporosis medications. This is a retrospective cohort using data from anonymised records and dispensation data ( www.sidiap.org ). Eligibility comprised the following: women aged ≥50, incident users of anti-osteoporosis medication (2012), with data available for at least 12 months prior to therapy initiation. Exclusions are other bone diseases/treatments and uncommon anti-osteoporosis drugs (N < 100). Follow-up was from first pharmacy dispensation until cessation, end of study, censoring or switching. Outcomes are 2- and 1-year persistence with a permissible gap of up to 90 days. Persistence with alendronate was compared to other bisphosphonates, strontium ranelate, selective oestrogen receptor modulators, teriparatide and denosumab. Cox models were used to estimate hazard ratios of therapy cessation according to drug used after adjustment for age, sex, BMI, smoking, alcohol drinking, Charlson co-morbidity index, previous fractures, use of anti-osteoporosis medication/s, oral corticosteroids and socio-economic status. A total of 19,253 women were included. Unadjusted 2-year persistence [95% CI] ranged from 10.3% [9.1-11.6%] (strontium ranelate) to 45.4% [43.1-47.8%] (denosumab). One-year persistence went from 35.8% [33.9%-37.7%] (strontium ranelate) to 65.8% [63.6%-68.0%] (denosumab). At the end of the first year and compared to alendronate users, both teriparatide and denosumab users had reduced cessation risk (adjusted HR 0.76, 95% CI 0.67-0.86 and 0.54, 95% CI 0.50-0.59 respectively) while at the end of the second year, only denosumab had a lower risk of discontinuation (adjusted HR 0.60, 95% CI 0.56-0.64). Unadjusted 2-year persistence is suboptimal. However, both teriparatide and denosumab users had better 1-year persistence and only denosumab had 2-year better persistence compared to alendronate users. Unmeasured confounding by indication might partially explain our findings.


Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia.
Activating mutations of receptor tyrosine kinases (RTKs) and their downstream affectors are common in acute myeloid leukemia (AML). We performed mutational analysis of FLT3, c-kit, c-fms, vascular endothelial growth factor (VEGF) receptors (Flt-1, KDR [kinase domain receptor]), and ras genes in a group of 91 pediatric patients with AML treated on Children's Cancer Group clinical trial CCG-2891. Forty-six percent of patients had activating mutations of FLT3 (24.5%), c-kit (3%), or ras (21%) genes. Mutation-positive patients had a higher median diagnostic white blood cell (WBC) count (71.5 vs 19.6 x 10(9)/L; P =.005) and lower complete remission rate (55% versus 76%; P =.046) than mutation-negative patients. The Kaplan-Meier estimate of overall survival (OS) for patients with and without an activating mutation was 34% versus 57%, respectively (P =.035). However, within this group, patients with FLT3/ALM (activation loop mutation) had good outcomes (OS, 86%). Exclusion of the FLT3/ALM from analysis decreased the OS for the remaining mutation-positive patients to 26% (P =.003). Ten of the 23 mutation-positive and 11 of the 34 mutation-negative patients received an allogeneic bone marrow transplant (BMT) in first complete remission (CR). In the mutation-positive group, the disease-free survival (DFS) for the allogeneic BMT recipients was 72% versus 23% for the 13 patients who received chemotherapy or autologous BMT (P =.01). DFS for the mutation-free patients with and without allogeneic BM transplantation was 55% and 40%, respectively (P =.38). Activating mutations in the RTK/ras signaling pathway are common in pediatric AML, and their presence may identify a population at higher risk of poor outcome who may benefit from allogeneic BM transplantation.


Organosulfates from pinene and isoprene over the Pearl River Delta, South China: seasonal variation and implication in formation mechanisms.
Biogenic organosulfates (OSs) are important markers of secondary organic aerosol (SOA) formation involving cross reactions of biogenic precursors (terpenoids) with anthropogenic pollutants. Until now, there has been rare information about biogenic OSs in the air of highly polluted areas. In this study, fine particle (PM2.5) samples were separately collected in daytime and nighttime from summer to fall 2010 at a site in the central Pearl River Delta (PRD), South China. Pinene-derived nitrooxy-organosulfates (pNOSs) and isoprene-derived OSs (iOSs) were quantified using a liquid chromatograph (LC) coupled with a tandem mass spectrometer (MS/MS) operated in negative electrospray ionization (ESI) mode. The pNOSs with MW 295 exhibited higher levels in fall (151 ± 86.9 ng m(-3)) than summer (52.4 ± 34.0 ng m(-3)), probably owing to the elevated levels of NOx and sulfate in fall when air masses mainly passed through city clusters in the PRD and biomass burning was enhanced. In contrast to observations elsewhere where higher levels occurred at nighttime, pNOS levels in the PRD were higher during the daytime in both seasons, indicating that pNOS formation was likely driven by photochemistry over the PRD. This conclusion is supported by several lines of evidence: the specific pNOS which could be formed through both daytime photochemistry and nighttime NO3 chemistry exhibited no day-night variation in abundance relative to other pNOS isomers; the production of the hydroxynitrate that is the key precursor for this specific pNOS was found to be significant through photochemistry but negligible through NO3 chemistry based on the mechanisms in the Master Chemical Mechanism (MCM). For iOSs, 2-methyltetrol sulfate ester which could be formed from isoprene-derived epoxydiols (IEPOX) under low-NOx conditions showed low concentrations (below the detection limit to 2.09 ng m(-3)), largely due to the depression of IEPOX formation by the high NOx levels over the PRD.


Cell-surface expression of a mutated Epstein-Barr virus glycoprotein B allows fusion independent of other viral proteins.
Epstein-Barr virus (EBV) infects human B lymphocytes and epithelial cells. We have compared the requirements for EBV glycoprotein-induced cell fusion between Chinese hamster ovary effecter cells and human B lymphoblasts or epithelial cells by using a virus-free cell fusion assay. EBV-encoded gB, gH, gL, and gp42 glycoproteins were required for efficient B cell fusion, whereas EBV gB, gH, and gL glycoproteins were required for Chinese hamster ovary effecter cell fusion with epithelial cell lines (AGS and SCC68) or the human embryonic kidney cell line 293-P. Fusion with human embryonic kidney 293-P cells was greater than fusion observed with B cells, indicative of an important role for cell contact. An antibody directed against the gH and gL complex inhibited epithelial cell fusion. Increased surface expression of gB alone as a result of truncations or point mutants in the carboxyl-terminal tail allowed gB-mediated fusion with epithelial cells, albeit at a lower level than with coexpression of gB, gH, and gL. Overall, gB appears to be the critical component for EBV glycoprotein-mediated cell fusion.


[Living with sexual diversity: experience report].
This study reports the experience of undergraduate students and faculty from the School of Nursing - Londrina State University, in a Civil Society Organization (CSO) that works with transvestites and men who provide sexual services for a fee. In the first school semester, students and faculty remained daily at CSO in order to care for immediate necessities and perform weekly lectures. In the second semester, workshops on sexual diversity were ministered by the transvestites to students and faculty followed by workshops, that were ministered, weekly, by students and faculty involving themes previously chosen by the transvestites. This experience is deemed to be enriching and contributes to students and faculty's personal and professional growth, as well as improves care quality and life quality of the transvestites.


Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients.
Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(+) group was significantly higher than in the HCV- group (37% vs. 22%, P <.001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P =.0001). Although survival has increased in the HCV- group in recent years, it has significantly decreased in HCV recipients (P <.0001). The main cause of death among the latter was decompensated graft cirrhosis (n = 23/105, 22%), whereas that of HCV- patients was infections (n = 10/52, 19%). Reasons for the recent worse outcome in HCV+ recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV+ recipients than among HCV- ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.


Cloning and characterization of the 5' region of the cell wall protein gene operon in Bacillus brevis 47.
Bacillus brevis 47 secretes vast amounts of proteins derived from both middle wall protein (MWP) and outer wall protein into the medium. The 5' region of the cell wall protein gene operon was cloned into Bacillus subtilis and subsequently into B. brevis 47. On the basis of the nucleotide sequence analysis, an open reading frame coding for MWP was identified on the cloned DNA fragment. Two potential translation initiation sites for the MWP gene are located tandemly in the same reading frame. Each of the sites contains a sequence highly homologous to the 3' end of B. brevis rRNA and an initiation codon. The translational fusion of the 5' region of the MWP gene with the Bacillus licheniformis alpha-amylase gene resulted in the efficient expression of the alpha-amylase gene in B. brevis 47. Of the two potential translation initiation sites, the one located upstream could be eliminated without affecting the expression of the MWP-alpha-amylase fusion gene, suggesting that MWP is synthesized in a precursor form with a signal peptide of 23 amino acid residues. S1 nuclease mapping of the cell wall protein gene transcripts suggested the possibility of the existence of several promoters in the 5' region within 300 base pairs from the translation initiation sites; one promoter was definitely localized within this part of the 5' region, and it was capable of expressing a heterologous gene fusion at a high level. The roles of the apparent structural complexity of the 5' region of the cell wall protein gene operon are discussed in connection with the efficient gene expression.


Automatic Approach Tendencies toward High and Low Caloric Food in Restrained Eaters: Influence of Task-Relevance and Mood.
Objective: Although restrained eaters are motivated to control their weight by dieting, they are often unsuccessful in these attempts. Dual process models emphasize the importance of differentiating between controlled and automatic tendencies to approach food. This study investigated the hypothesis that heightened automatic approach tendencies in restrained eaters would be especially prominent in contexts where food is irrelevant for their current tasks. Additionally, we examined the influence of mood on the automatic tendency to approach food as a function of dietary restraint. Methods: An Affective Simon Task-manikin was administered to measure automatic approach tendencies where food is task-irrelevant, and a Stimulus Response Compatibility task (SRC) to measure automatic approach in contexts where food is task-relevant, in 92 female participants varying in dietary restraint. Prior to the task, sad, stressed, neutral, or positive mood was induced. Food intake was measured during a bogus taste task after the computer tasks. Results: Consistent with their diet goals, participants with a strong tendency to restrain their food intake showed a relatively weak approach bias toward food when food was task-relevant (SRC) and this effect was independent of mood. Restrained eaters showed a relatively strong approach bias toward food when food was task-irrelevant in the positive condition and a relatively weak approach in the sad mood. Conclusion: The weak approach bias in contexts where food is task-relevant may help high-restrained eaters to comply with their diet goal. However, the strong approach bias in contexts where food is task-irrelevant and when being in a positive mood may interfere with restrained eaters' goal of restricting food-intake.