Molecular and antigenic characterization of triple-reassortant H3N2 swine influenza viruses isolated from pigs, turkey and quail in Canada.
In 2005, triple-reassortant H3N2 (trH3N2) influenza A viruses were isolated from swine and turkeys in Canada. Subsequently, these viruses were isolated from humans and mink in 2006 and 2007, respectively. Following full genome sequencing, H3N2 viruses isolated from turkeys (2005), quail (2008) and swine (2009) in Canada, were characterized as trH3N2. The 2005 turkey isolate was found to be almost identical to other viruses isolated in that year, with quail and pig isolates related very closely to the 2005 trH3N2. Minimal antigenic evolution of the swine isolates relative to the reference 2005 virus was observed. These results suggest the establishment of a stable lineage of trH3N2 in Canadian pigs, with evidence for interspecies transmission to turkeys and quails.


Professional background and the comprehension of family-centredness of rehabilitation for children with cerebral palsy.
Children with cerebral palsy have difficulties in several areas of functioning, and they need long-lasting rehabilitation with a clear focus on the individual's needs. Finnish guidelines emphasize family-centred service. The values of family-centred service are widely known, but how the principles of family-centred service are adopted in clinical practice is not well documented. The objective of this study was to analyse the family-centred behaviour of professionals working with children and adolescents with cerebral palsy. A translated version of the Measure of Processes of Care for Service Providers (MPOC-SP) questionnaire was used to evaluate the family-centred service. The questionnaire was sent to all the professionals in the multidisciplinary rehabilitation teams at all the hospitals and governmental special schools treating children and adolescents with cerebral palsy in Finland (n= 327). Furthermore, 438 physiotherapy service providers working in the children's home region were invited to participate. A total of 201 multidisciplinary team members and 311 physiotherapy service providers completed the questionnaire. Both the team members and the service providers generally rated their family-centred behaviour positively. There was statistically significant difference in how the team members in the multidisciplinary teams self-assessed their family-centred service. Physiotherapists working in multidisciplinary teams rated their family-centred service higher than physiotherapy service providers. The professional's apprehension of family-centred service increased with work experience. Professional background and professional context seem to affect the apprehension of family-centred service. Also work experience and being part of a multidisciplinary team have an influence on how the professionals embrace the family-centred service delivered. The MPOC-SP can be used to identify areas for improvement.


Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden.
To provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration. Patients ≥16 years assigned an RA diagnosis were identified from inpatient (n=96 560; 1964-2007) and specialist outpatient care (n=56 336; 2001-2007) in the Swedish National Patient Register, and the Swedish Rheumatology Quality Register (n=21 242; 1995-2007). Data on prescriptions, demography, vital status and educational level were retrieved from national registers. A total of 58 102 individuals (mean age 66 years; 73% women) assigned an RA diagnosis were alive in Sweden in 2008, corresponding to a cumulative prevalence of 0.77% (women 1.11%, men 0.43%). The 2001-2007 period prevalence was 0.70%. Restriction to patients with ≥2 visits or diagnosis from a rheumatologist/internist reduced the overall cumulative prevalence to 0.68%. Whereas urban/rural differences (crude 0.65-1.00%) were explained by age differences, the age/sex-adjusted prevalence remained higher in patients with ≤9 years education (0.86%) than for those with 10-12 years (0.82%) and >12 years (0.65%). Treatment exposures (76% any disease-modifying antirheumatic drugs (DMARDs) or steroids, 64% any DMARD, 15% biological agents) varied with age; use of biological agents decreased from 22% in 16-59 years olds to 3% in ≥80 years olds. Any DMARD use correspondingly decreased from 71% to 43%. Applying age cut-off points from previous northern European and North American prevalence studies reduced or eliminated between-study differences. This nationwide approach yielded a prevalence of RA similar to previous regional assessments. While displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level. Although most patients received antirheumatic drugs, age was a strong treatment determinant.


An epidemiological study of childhood development in an urban setting in Brazil.
Mental illness is an important public health concern, often starting early in life and particularly impacting children from low-and middle-income countries. Our aims were to 1) determine, in a representative sample of public preschool 4- to 5-year old children in Brazil, the prevalence of internalizing and externalizing disorders and socioemotional development delays; and 2) to identify modifiable risk factors associated with mental, behavioral, or developmental disorders (MBDD), such as microsystem (i.e., parent-child relationship), mesosystem (social support), and macrosystem contextual factors (neighborhood disadvantage). A random sample of public preschool children was recruited in the city of Embu das Artes (São Paulo metropolitan area) (n=1,292 from 30 public preschools). Six-month prevalence of MBDD was measured using the Child Behavior Checklist (CBCL) and the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE). Six-month prevalence estimates were 25.4% for internalizing disorders, 12.1% for externalizing disorders, and 30.3% for socioemotional development delays. MBDD prevalence estimates were higher in families with stressful relationships and parental depression or anxiety, and in families with lower social capital. At least 25% of preschool children living in an urban area in Brazil presented a mental health disorder. These mental disorder were associated with modifiable factors such as stressful family relationships and lower social capital. Prevention and intervention measures such as family therapy are needed to decrease such high prevalence.


Mini- versus standard percutaneous nephrolithotomy for treatment of pediatric renal stones: is smaller enough?
Miniaturized percutaneous nephrolithotomy (PCNL) has gained increased popularity owing to efforts in recent years to lower peri-operative morbidity while maintaining a high stone-free rate (SFR). The outcomes of pediatric renal stones treated by mini-PCNL (MPCNL) versus standard PCNL (SPCNL) were retrospectively assessed. A retrospective data analysis of 134 consecutive patients younger than 17 years who underwent PCNL between January 2014 and July 2018 was performed. The patients were categorized into two treatment groups depending on the tract size and instruments used. Seventy-five patients were treated by SPCNL using adult instruments via a 22-26 Fr tract, and 59 patients were treated by MPCNL using pediatric instruments via a 16-20 Fr tract. A total of 134 children (SPCNL = 75; MPCNL = 59) underwent PCNL and subsequent evaluation. Patient demographics and stone characteristics were comparable between the two groups. The mean stone size ranged from 1.9 ± 1.162 cm in the MPCNL group to 2.2 ± 1.424 cm in the SPCNL group, and the overall SFR was 89.5% in the MPCNL group and 94.7% in the SPCNL group. When comparing the common characteristics, no significant difference was found between the two surgical access regarding the mean operative duration, SFR, incidence of peri-operative complications, and the rate of bleeding requiring a blood transfusion. Conversely, the mean postoperative hemoglobin decrease was significantly lower in the MPCNL group relative to the SPCNL group, at 0.354 ± 0.299 g versus 0.568 ± 0.332 g, respectively (P = 0.001). In addition, the mean duration of hospitalization was significantly lower in the MPCNL group than in the SPCNL group, at 1.91 ± 1.154 days compared with 2.41 ± 1.14 days, respectively (P = 0.014). Herein, the authors report the first systematic review of the first center in the locality treating this cross section of patients. This review reveals that the use of these smaller instruments can deliver a strong safety profile while achieving good stone clearance. As an alternative to decreasing the peri-operative morbidity associated with SPCNL, MPCNL can be conveniently used without affecting the outcomes of the procedure. It is a safe and feasible procedure for maximal clearance of stones and should comprise the treatment of choice-regardless of age-for experienced endourologists. MPCNL represents a valuable way of treating simple and complex renal stones in children, with an operative time, SFR, and overall complication rate comparable with those of SPCNL. Mini-PCNL resulted in shorter hospitalization and fewer hemoglobin drops.


From memory to prospection: what are the overlapping and the distinct components between remembering and imagining?
Reflecting on past events and reflecting on future events are two fundamentally different processes, each traveling in the opposite direction of the other through conceptual time. But what we are able to imagine seems to be constrained by what we have previously experienced, suggesting a close link between memory and prospection. Recent theories suggest that recalling the past lies at the core of imagining and planning for the future. The existence of this link is supported by evidence gathered from neuroimaging, lesion, and developmental studies. Yet it is not clear exactly how the novel episodes people construct in their sense of the future develop out of their historical memories. There must be intermediary processes that utilize memory as a basis on which to generate future oriented thinking. Here, we review studies on goal-directed processing, associative learning, cognitive control, and creativity and link them with research on prospection. We suggest that memory cooperates with additional functions like goal-directed learning to construct and simulate novel events, especially self-referential events. The coupling between memory-related hippocampus and other brain regions may underlie such memory-based prospection. Abnormalities in this constructive process may contribute to mental disorders such as schizophrenia.


A mutation in the cystic fibrosis transmembrane conductance regulator gene associated with elevated sweat chloride concentrations in the absence of cystic fibrosis.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been shown to cause cystic fibrosis (CF) and male infertility due to congenital bilateral absence of the vas deferens. We report the identification of a 6.8 kb deletion (del14a) and a nonsense mutation (S1455X) in the CFTR genes of a mother and her youngest daughter with isolated elevated sweat chloride concentrations. Detailed clinical evaluation of both individuals found no evidence of pulmonary or pancreatic disease characteristic of CF. A second child in this family with classic CF was homozygous for the del14a mutation, indicating that this mutation caused severe CFTR dysfunction. CFTR mRNA transcripts bearing the S1455X mutation were stable in vivo , implying that this allele encoded a truncated version of CFTR missing the last 26 amino acids. Loss of this region did not affect processing of transiently expressed S1455X-CFTR compared with wild-type CFTR. When expressed in CF airway cells, this mutant generated cAMP-activated whole-cell chloride currents similar to wild-type CFTR. Preservation of chloride channel function of S1455X-CFTR was consistent with normal lung and pancreatic function in the mother and her daughter. These data indicate that mutations in CFTR can be associated with elevated sweat chloride concentrations in the absence of the CF phenotype, and suggest a previously unrecognized functional role in the sweat gland for the C-terminus of CFTR.


Physician board certification in hospice and palliative medicine.
The American Board of Hospice and Palliative Medicine (ABHPM) was formed in 1995 to establish and implement standards for certification of physicians practicing hospice and palliative medicine and, ultimately, accreditation of physician training in this discipline. The ABHPM has created a certification process that parallels other member boards of the American Board of Medical Specialties (ABMS). After 3(1/2) years and the administration of seven examinations, 623 physicians have achieved board certification in hospice and palliative medicine. Those with ABMS primary board certifications have been certified by anesthesiology, 4%; family practice, 23%; internal medicine, 55%; pediatrics, 1%; radiation oncology, 2%; and surgery, 2%. The majority describe their practice location as urban. Sixty-nine percent report more than 5 years of clinical experience in hospice/palliative medicine and 75% report an association with a hospice as medical director or hospice physician. Sixty-seven percent belong to the American Academy of Hospice and Palliative Medicine. Applicants were drawn from 48 states, Canada, and 3 foreign countries. The available data indicate only 20% were less than 40 years of age and that two-thirds were men. There is significant physician interest in seeking professional recognition of expertise in caring for terminally ill persons and their families through creation of a specialty in hospice and palliative medicine. Certification of physicians and accreditation of training programs are key elements in this process. This process will encourage more physicians to enter this field and provide needed expertise in the management of patients with progressive disease for whom the prognosis is limited, and the focus of care is quality of life.


Phonon excitations of composite-fermion landau levels.
Phonon excitations of fractional quantum Hall states at filling factors nu = 1/3, 2/5, 4/7, 3/5, 4/3, and 5/3 are experimentally shown to be based on Landau-level transitions of composite fermions. At filling factor nu = 2/3, however, a linear field dependence of the excitation energy in the high-field regime rather hints towards a spin transition excited by the phonons. We propose to explain this surprising observation by an only partially polarized 2/3 ground state, making the energetically lower lying spin transition also allowed for phonon excitations.


Annulus Fibrosus Repair Using High-Density Collagen Gel: An In Vivo Ovine Model.
Ovine in vivo study. To perform lateral approach lumbar surgery in an ovine model to administer an injectable riboflavin cross-linked high-density collagen (HDC) gel and to assess its ability to mitigate intervertebral disc (IVD) degeneration after induced annulus fibrosus (AF) injury. Biological-based injectable gels have shown efficacy in restoring biomechanical, radiographic, and histological parameters in IVD-injured animal models. Riboflavin cross-linked HDC gel has previously demonstrated retention of nucleus pulposus (NP) tissue, reduced loss of disc height, and prevention of terminal cellular degenerative changes in rat-tail spines. However, this biological therapy has never been tested in large animal models. Forty lumbar IVDs were accessed from eight sheep via lateral approach surgery. IVDs were randomly assigned to healthy control, injury and HDC treatment, or negative control with injury and no treatment. IVD injury was carried out using a drill-bit through the AF followed by needle puncture of the NP. Sheep were followed for 16 weeks and underwent qualitative/quantitative magnetic resonance imaging, x-ray, and histological analyses of collagen and proteoglycan content. The lateral approach to the ovine lumbar spine to deliver HDC gel proved to be safe and reproducible. IVDs treated with the HDC gel revealed less degenerative changes at the microscopic level based on AF and NP histology. However, mean Pfirrmann grade, T2 relaxation time, NP voxel size, and disc height index were not significantly different between the two injury groups. Injectable HDC gel can be administered safely via lateral approach surgery in an ovine AF injury model. IVDs treated with HDC gel demonstrated less degeneration at the microscopic level though radiographic changes were slight when comparing treated to untreated IVDs. Future studies will need to elucidate the role of injury technique and time frame for follow-up in correlating histological and radiographical outcomes. N /A.


Global Proteomic Profiling of Piscirickettsia salmonis and Salmon Macrophage-Like Cells during Intracellular Infection.
Piscirickettsiasalmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with numerous negative impacts in the Chilean salmon farming industry. Although transcriptomic studies of P. salmonis and its host have been performed, dual host-pathogen proteomic approaches during infection are still missing. Considering that gene expression does not always correspond with observed phenotype, and bacteriological culture studies inadequately reflect infection conditions, to improve the existing knowledge for the pathogenicity of P. salmonis, we present here a global proteomic profiling of Salmon salar macrophage-like cell cultures infected with P. salmonis LF-89. The proteomic analyses identified several P. salmonis proteins from two temporally different stages of macrophages infection, some of them related to key functions for bacterial survival in other intracellular pathogens. Metabolic differences were observed in early-stage infection bacteria, compared to late-stage infections. Virulence factors related to membrane, lipopolysaccharide (LPS) and surface component modifications, cell motility, toxins, and secretion systems also varied between the infection stages. Pilus proteins, beta-hemolysin, and the type VI secretion system (T6SS) were characteristic of the early-infection stage, while fimbria, upregulation of 10 toxins or effector proteins, and the Dot/Icm type IV secretion system (T4SS) were representative of the late-infection stage bacteria. Previously described virulence-related genes in P. salmonis plasmids were identified by proteomic assays during infection in SHK-1 cells, accompanied by an increase of mobile-related elements. By comparing the infected and un-infected proteome of SHK-1 cells, we observed changes in cellular and redox homeostasis; innate immune response; microtubules and actin cytoskeleton organization and dynamics; alteration in phagosome components, iron transport, and metabolism; and amino acids, nucleoside, and nucleotide metabolism, together with an overall energy and ATP production alteration. Our global proteomic profiling and the current knowledge of the P. salmonis infection process allowed us to propose a model of the macrophage-P. salmonis interaction.


Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction.
Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogen-detoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR.


Rapid degradation of PrxI and PrxII induced by silica in Rat2 cells.
Peroxidases of the peroxiredoxin (Prx) family catalyze the reduction of H(2)O(2) and lipid peroxides. The effects of H(2)O(2), 12-O-tetradecanoylphorbol 13-acetate (TPA), and silica on the abundance of two cytosolic isoforms of Prx (PrxI and PrxII) were examined in Rat2 cells. TPA induces the production of reactive oxygen species (ROS) in various mammalian cell types, and silica induces the production of ROS in Rat2 cells. Whereas H(2)O(2) and TPA did not affect the concentration of PrxI or Prx II, silica triggered a rapid degradation of both Prx enzymes. Silica also induced degradation of the NF-kappaB inhibitor IkappaB-alpha. N-Acetylcysteine and diphenyleneiodonium, both of which inhibit the accumulation of intracellular ROS, each blocked silica-induced degradation of IkappaB-alpha but had no effect on that of the Prx enzymes, suggesting that ROS do not contribute to Prx proteolysis. The silica-induced degradation of Prx enzymes was also insensitive to the proteasome inhibitors MG132 and lactacystin, whereas IkappaB-alpha proteolysis was completely blocked by these inhibitors. Experiments with the Ca(2+) ionophore A23187 indicated that a Ca(2+)-dependent protease such as calpain might contribute substantially to silica-induced degradation of PrxII, but only moderately to that of PrxI. These results indicate that silica increases cellular oxidative stress not only by inducing ROS production, but also by triggering the degradation of Prx enzymes that are responsible for elimination of cellular ROS. Such aggravated oxidative stress might be important in the initial pathogenesis of silica-associated pulmonary diseases.


[Does the selection of fox for tame and aggressive behavior changes their ability to focus attention, and training the motor skills?].
Foxes long time selected for tame and aggressive behavior were compared on ability to focus attention on the object of food reinforcement. Attenuation of this behavior and rate of training for motor skills also has been examined. Maximal duration of eye focusing was significantly higher in aggressive foxes, in comparison with tame ones. Our experiments allowed divide the group of tame foxes into two subgroups "calm" and "emotional", on the base of emotionality and motor activity during tests. Features of behavior of these two subgroups steadily differed in all tests. "Calm" tame foxes at the extinction test continued the trained skill longer than "emotional" and aggressive ones. Tame foxes were more successful than aggressive in the training for motor skills. The possible reasons of the data obtained are discussed.


Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer's disease.
Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs. Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14-17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running. Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins. Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.


Kinetic bacterial bioluminescence assay for contact sediment toxicity testing: relationships with the matrix composition and contamination.
The present study represents the first broader evaluation of the rapid 30-s kinetic bioluminescence assay with Vibrio fisheri (microplate format modification) for contact toxicity testing of whole sediments. The present study focused on river sediments from the Morava River basin, Czech Republic, repeatedly sampled during 2005 to 2006 and analyzed for geological and geochemical parameters, content of toxic metals, major organic pollutants, and toxicity. High natural variation in toxicity (50% inhibitory concentration [IC50] values ranging from 0.8 to >80 mg sediment dry wt/ml) was found (among different sampling periods and years, among sites), and this could be related to the sediment dynamics affected by spring high flows and summer droughts. From the 46 sediment descriptors, exchangeable protons (H(+)) was the only parameter that consistently correlated with toxicity. Three other descriptors (i.e., content of organic carbon plus two parameters from the detailed silicate analysis of sediments: percentage of SO(3) representing total sulfur content, structural water H(2)O+) also significantly correlated with toxicity. There were only minor and variable correlations with contamination. We propose sediment safety guideline categories for the V. fisheri kinetic test with severe toxicity threshold of IC50 < 1 mg dry wt/ml. Although sediments are considered a rather stable matrix in comparison with river water, we confirmed high variability and dynamics that should be reflected in monitoring plans and field studies.


Bacteraemia with Moryella indoligenes and Fastidiosipila sanguinis: a case report.
Moryella indoligenes and Fastidiosipila sanguinis are obligate anaerobic Gram-positive bacteria that are rarely involved in human infections. We present the first case of bacteraemia with M. indoligenes , which was part of a co-infection with F. sanguinis . Both micro-organisms were identified by 16S rRNA gene sequencing and M. indoligenes was also identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Prostate cancer involving the bladder suggests that the urinary tract was the most likely primary site of infection.


Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin.
The indiscriminate use, abuse and patients' noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.


The importance of patient selection for photochemotherapy in psoriasis.
Twenty-four patients with psoriasis were treated with orally administered 8-methoxypsoralen followed by exposure to high-intensity long-wavelength ultraviolet radiation (PUVA) at a psoriasis day care centre. Among the 20 with plaque type psoriasis the condition cleared in 13 (65%), after a mean of 20.7 treatment sessions, and improved but failed to clear in 4 (20%); the treatment failed in the other 3 (15%). The other four patients had erythrodermic, pustular or inflammatory psoriasis, and all failed to respond to PUVA therapy. Factors to be considered in patient selection for this form of therapy are the type of psoriasis, the patient's skin type and th proportion of the body surface area involved.


In-hospital source of airborne Penicillium species spores.
Between 16 July and 1 October 1984, prospectively monitored corridor air samples from a bone marrow transplant station revealed a marked increase in airborne thermotolerant Penicillium spores. Simultaneous cultures of outside air showed lower spore counts, which were unchanged before, during, and after the corridor outburst, establishing that the source was within the hospital. Although the corridor was equipped with recirculating high-efficiency particulate air filtration units which provided 16 air changes per h, the mean corridor air count rose to 64.4 thermotolerant Penicillium CFU/m3 during the outburst period. The in-hospital source was ultimately traced to rotting cabinet wood enclosing a sink with leaking pipes in the medication room. It produced approximately 5.5 X 10(5) thermotolerant Penicillium CFU/h. In a patient room supplied by corridor air, an in-room recirculating high-efficiency particulate air filter reduced the mean thermotolerant Penicillium count to 2.2 CFU/m3. No patient illness or colonization occurred as a result of this event, although the cabinet wood, after sterilization, was shown to sustain abundant growth of Aspergillus fumigatus and Aspergillus flavus. Wet organic substrates should be avoided in hospital areas with immunosuppressed patients.


Chloroplast genome variation and phylogenetic relationships of Atractylodes species.
Atractylodes DC is the basic original plant of the widely used herbal medicines "Baizhu" and "Cangzhu" and an endemic genus in East Asia. Species within the genus have minor morphological differences, and the universal DNA barcodes cannot clearly distinguish the systemic relationship or identify the species of the genus. In order to solve these question, we sequenced the chloroplast genomes of all species of Atractylodes using high-throughput sequencing. The results indicate that the chloroplast genome of Atractylodes has a typical quadripartite structure and ranges from 152,294 bp (A. carlinoides) to 153,261 bp (A. macrocephala) in size. The genome of all species contains 113 genes, including 79 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. Four hotspots, rpl22-rps19-rpl2, psbM-trnD, trnR-trnT(GGU), and trnT(UGU)-trnL, and a total of 42-47 simple sequence repeats (SSR) were identified as the most promising potentially variable makers for species delimitation and population genetic studies. Phylogenetic analyses of the whole chloroplast genomes indicate that Atractylodes is a clade within the tribe Cynareae; Atractylodes species form a monophyly that clearly reflects the relationship within the genus. Our study included investigations of the sequences and structural genomic variations, phylogenetics and mutation dynamics of Atractylodes chloroplast genomes and will facilitate future studies in population genetics, taxonomy and species identification.


Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence.
Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of Ldlr -/- mice on a high-cholesterol diet during lesion progression and regression phases. We found that the evolutionarily conserved lncRNA small nucleolar host gene-12 (SNHG12) is highly expressed in the vascular endothelium and decreases during lesion progression. SNHG12 knockdown accelerated atherosclerotic lesion formation by 2.4-fold in Ldlr -/- mice by increased DNA damage and senescence in the vascular endothelium, independent of effects on lipid profile or vessel wall inflammation. Conversely, intravenous delivery of SNHG12 protected the tunica intima from DNA damage and atherosclerosis. LncRNA pulldown in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that SNHG12 interacted with DNA-dependent protein kinase (DNA-PK), an important regulator of the DNA damage response. The absence of SNHG12 reduced the DNA-PK interaction with its binding partners Ku70 and Ku80, abrogating DNA damage repair. Moreover, the anti-DNA damage agent nicotinamide riboside (NR), a clinical-grade small-molecule activator of NAD+, fully rescued the increases in lesional DNA damage, senescence, and atherosclerosis mediated by SNHG12 knockdown. SNHG12 expression was also reduced in pig and human atherosclerotic specimens and correlated inversely with DNA damage and senescent markers. These findings reveal a role for this lncRNA in regulating DNA damage repair in the vessel wall and may have implications for chronic vascular disease states and aging.


Hydroperoxide metabolism in trout gill tissue: effect of glutathione on lipoxygenase products generated from arachidonic acid and docosahexaenoic acid.
The generation of oxygenated products from arachidonic acid and docosahexaenoic acid by the n-9 lipoxygenase of trout gill was monitored as a function of substrate concentration and added glutathione. In the absence of added glutathione up to 50% of the substrate consumed by the lipoxygenase was ultimately converted non-enzymatically to trihydroxy derivatives of the initial n-9 hydroperoxide enzyme product. The presence of added glutathione progressively increased conversion of the respective fatty acid hydroperoxides to the n-9 monohydroxy derivatives of arachidonic and docosahexaenoic acids while concomitantly decreasing the yield of trihydroxy derivatives, consistent with its role as a cosubstrate in the peroxidase reaction. The stability and net turnover of the lipoxygenase were also significantly improved by the addition of glutathione. The relative distribution of monohydroxy and trihydroxy products from either arachidonic acid or docosahexaenoic acid were similarly affected and equally sensitive to the glutathione concentration. These data suggest that in animals, the hydroperoxides of n-6 and n-3 polyunsaturated fatty acids generated by lipoxygenases are equally metabolized by the peroxide scavenging capabilities of the tissue.


From the Cover: Drug-Induced Taste Disorders in Clinical Practice and Preclinical Safety Evaluation.
More than 200 medications can induce taste disorders in patients. They not only reduce quality of life for those affected, but can lead to malnutrition, severe dehydration and difficulty in maintaining a therapeutic regimen. Nevertheless, the impact of drug candidates on taste is rarely evaluated in preclinical toxicology studies during the early stage of drug development. Moreover, knowledge about how to investigate these adverse effects is scarce in the toxicology field. Here, we discuss the clinical status of drug-induced taste disorders in patients, with the goal of providing toxicologists with a broad understanding of its prevalence, and how stressful and even dangerous it can be to affected patients. Because taste, smell, and oral trigeminal sensation are highly interdependent, we also address drug-induced changes in olfactory and oral somatosensory perceptions. We then review the biology of the gustatory system (including anatomy and histology), and the latest developments about how taste contributes to flavor perception. Finally, we feature recently optimized preclinical approaches to investigate drug-induced taste change in animal models, including morphological evaluation of taste buds and taste cells, gustatory nerve recording, and behavioral testing. Our goals are to raise awareness of drug-induced taste disorders among toxicologists, share an overview of new approaches and key studies that can be used to identify drug-induced gustatory system toxicity early in the drug development process, and to stimulate further research at this emerging interface of chemosensory disorders with toxicology.


Arabinogalactan proteins in root and pollen-tube cells: distribution and functional aspects.
Arabinogalactan proteins (AGPs) are complex proteoglycans of the cell wall found in the entire plant kingdom and in almost all plant organs. AGPs encompass a large group of heavily glycosylated cell-wall proteins which share common features, including the presence of glycan chains especially enriched in arabinose and galactose and a protein backbone particularly rich in hydroxyproline residues. However, AGPs also exhibit strong heterogeneities among their members in various plant species. AGP ubiquity in plants suggests these proteoglycans are fundamental players for plant survival and development. In this review, we first present an overview of current knowledge and specific features of AGPs. A section devoted to major tools used to study AGPs is also presented. We then discuss the distribution of AGPs as well as various aspects of their functional properties in root tissues and pollen tubes. This review also suggests novel directions of research on the role of AGPs in the biology of roots and pollen tubes.


Ceramide : A New Target in Anticancer Research?
An astute observer of chemotherapeutic progress concedes that anticancer research is, in effect, often more empirical that rational, and there are those who maintain that little gain has been made in the therapeutic outcome of cancer patients in the past 60 years, thus, questioning the wisdom of continued expenditure of funds for research in cancer chemotherapy. Half a decade ago few would have denied the importance of regarding the intimate drug-target interactions in cell death or in resistance thereof. However, the heretofore-parochial approach to drug screening and rationalization of structure-activity based on specific drug-target interactions has met with limited success. This standpoint has forced investigators to explore new and certainly provocative interpretations, which necessitate radical departure from accepted but perhaps outworn concepts of the action of drugs. The recent identification of a ceramide mediated apoptotic signaling pathway triggered by antitumor agents may offer new insights into mechanism of action of chemo- and radio-therapy. This review is intended to initiate a debate on the role of ceramide in apoptosis signaling: is it a consequence of cell damage, or part of an independent cytotoxic pathway ?


[Effect of enteroviruses on the ecology of intestinal bacteria].
The rate of isolation of some enteric bacteria from normal children and those suffering from diseases caused by ECHO viruses was studied. Enterovirus infection was shown to cause characteristic disturbance of microbial biocenosis in the large intestine differing from similar disorders in other intestinal diseases: a decrease in the total number of enterobacteria with predominant replication of escherichia not fermenting lactose. Enteroviruses exert a mediated effect on enteric microorganism population changing the physico-chemical properties of their environment.


Sepsis increases contraction-related generation of reactive oxygen species in the diaphragm.
Recent work indicates that free radicals mediate sepsis-induced diaphragmatic dysfunction. These previous experiments have not, however, established the source of the responsible free radical species. In theory, this phenomenon could be explained if one postulates that sepsis elicits an upregulation of contraction-related free radical formation in muscle. The purpose of the present study was to test this hypothesis by examination of the effect of sepsis on contraction-related free radical generation [i.e. , formation of reactive oxygen species (ROS)] by the diaphragm. Rats were killed 18 h after injection with either saline or endotoxin. In vitro hemidiaphragms were then prepared, and ROS generation during electrically induced contractions (20-Hz trains delivered for 10 min) was assessed by measurement of the conversion of hydroethidine to ethidium. ROS generation was negligible in noncontracting diaphragms from both saline- and endotoxin-treated groups (2.0 +/- 0. 6 and 2.8 +/- 1.0 ng ethidium/mg tissue, respectively), but it was marked in contracting diaphragms from saline-treated animals (19.0 +/- 2.8 ng/mg tissue) and even more pronounced (30.0 +/- 2.8 ng/mg tissue) in diaphragms from septic animals (P < 0.01). This enhanced free radical generation occurred despite the fact that the force-time integral (i.e., the area under the curve of force vs. time) for control diaphragms was higher than that for the septic group. In additional studies, in which we altered the stimulation paradigm in control muscles to achieve a force-time integral similar to that achieved in septic muscles, an even greater difference between control and septic muscle ROS formation was observed. These data indicate that ROS formation during contraction is markedly enhanced in diaphragms from endotoxin-treated septic animals. We speculate that ROS generated in this fashion plays a central role in producing sepsis-related skeletal muscle dysfunction.


Review of stem cell-based therapy for the treatment of cardiovascular disease.
Cardiovascular disease remains the number one cause of mortality in the United States. Nearly 2,400 Americans die of cardiovascular disease each day, an average of 1 every 37 s. One in three Americans has been diagnosed with one or more forms of cardiovascular disease. Most recent estimates show that, in the United States alone, 16 million people have coronary artery disease and 5.3 million have been diagnosed with heart failure. Unlike other forms of cardiovascular disease, heart failure is often the end-stage of a cardiovascular disease, frequently coronary artery disease. The 1-year mortality of people diagnosed with heart failure remains a sobering 20%. Heart failure is also very costly. The estimated direct and indirect cost of heart failure in the US for 2008 is 34.8 billion dollars. Therefore, advanced treatment options for these populations could greatly impact patient health outcomes and cost savings. Even with the advancements in pharmacologic therapies and improvements in mechanical support devices, the only definitive treatment for advanced heart failure remains heart transplantation. Given the limited availability of donor organs for use in orthotopic heart transplantation, alternative therapies including stem cell-based therapies have been explored. The past decade has seen an explosion of activity of the field of cardiac regeneration. New scientific techniques and discoveries have allowed rapid advancements but there have also been conflicting opinions and results. The concept of cardiac regeneration is now commonly accepted but the exact mechanisms and extent of regeneration is greatly debated. Several candidate cell populations, both cardiac and extracardiac, have been reported to be capable of cardiac regeneration. However, some studies question if these cell populations actually differentiate into cardiomyocytes but rather function through paracrine effects or through cell fusion. Despite these challenges, the field has also begun translating the preclinical animal studies into human clinical trials using several cell types for the treatment of many clinical disease states. This review will highlight the preclinical animal studies and review the results of the published clinical trials.


Proteomic analysis of salivary acidic proline-rich proteins in human preterm and at-term newborns.
A 1 year follow-up investigation of salivary acidic proline-rich proteins (aPRPs) in preterm and at-term newborns using HPLC-ESI-IT-MS showed that (i) this class of proteins is constitutive rather than inducible, as it is still found in the oral cavity of preterm newborns from 180 days of postconception age (PCA); (ii) the expression of PRH-2 locus anticipates that of PRH-1, since Db isoforms are expressed some months after the PRP-1 and PRP-2 isoforms. The evaluation of the relative abundances of the different aPRPs isoforms and derivatives (differently phosphorylated and cleaved) as a function of PCA showed that (iii) the proteolytic enzymes generating truncated isoforms are also constitutive because they are fully active since 180 days of PCA; (iv) the kinase involved in aPRP phosphorylation is not fully mature in preterm newborns, but its activity increases with PCA, synchronizing with that of at-term newborns and reaching the adult levels at about 500-600 days of PCA, in concomitance with the beginning of deciduous dentition.


Induction of clusterin in tubules of nephrotic rats.
Clusterin is a glycoprotein induced after renal tubular cell injury. The purpose of this study was to examine the expression of clusterin in a disease model characterized early in its course by predominant glomerular injury. Male Wistar rats (weighing 251 +/- 16 g) were treated with puromycin aminonucleoside (PAN: 15 mg/100 g body wt, subcutaneously; n = 7) or vehicle (control; n = 8). The kidneys were harvested 6 d after treatment, when rats were nephrotic. Clusterin mRNA was markedly induced in the kidneys of nephrotic rats (8.5-fold versus control). Immunohistochemistry studies demonstrated clusterin primarily in tubules in the cortex and medulla. Many of the tubules staining for clusterin were dilated but had no other differentiating morphologic features. Increased numbers of proliferating tubular cells were seen at 6 d, but there was no correlation between these cells and clusterin staining. In contrast to the extent and pattern of clusterin staining, vimentin was seen in only sporadic, dilated tubules, in addition to its expected glomerular localization. An increase in clusterin mRNA was not seen 1, 2, or 4 d after PAN injection. In conclusion, tubular epithelial cell induction of clusterin occurs in the kidneys of nephrotic rats. The appearance of clusterin precedes the development of tubulointerstitial disease and may be a response to the proteinuria.


HIV/AIDS knowledge, behaviour and beliefs among South African university students.
Globally, South Africa has the highest prevalence of HIV/AIDS. In the absence of cure, prevention is the only available method to reduce HIV prevalence rates. This can only be obtained through behavioural change, which is associated with a good knowledge about HIV. The study aims to determine the knowledge, beliefs, behaviours and sources of HIV and AIDS information among university students at two tertiary institutions in South Africa. The study was a quantitative, cross-sectional, descriptive and comparative survey. Students from the Western Cape Province and the KwaZulu-Natal Province participated in the study. The main findings of the study were that although students had an adequate general knowledge on HIV/AIDS, both groups scored the lowest in the transmission modes of HIV. The media was the main source of HIV/AIDS information for students and university health care facilities need to be more proactive in informing students about the transmission of HIV/AIDS.


Acridine orange fluorescent microscopy is more sensitive than India ink light microscopy in the rapid detection of cryptococcosis among CrAg positive HIV patients.
India ink microscopy on cerebrospinal fluid is still utilized in resource limited settings for the diagnosis of cryptococcal meningitis despite its poor sensitivity. We hypothesized that staining fungal nucleic acids with fluorescent dyes instead of the capsule with India ink might improve sensitivity for the diagnosis of cryptococcal meningitis. We enrolled 96 HIV-infected participants with cryptococcal meningitis who provided 194 CSF specimens at serial time points in Kampala, Uganda. Cryptococcosis was diagnosed by cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) test and only positive samples were included. We stained CSF with India ink and acridine orange. We cultured the same samples on standard fungal media. We compared acridine orange to CrAg, India ink and CSF culture. Acridine orange was more sensitive (96%) than India ink (79%) with reference to CSF CrAg. Acridine orange and India ink had a statistically significant difference (P<0.001) with a 25% correlation for detection of Cryptococcus yeasts. India ink had more negative results (22%) than acridine orange (4%). The sensitivity for India ink increased (86%) while that of acridine orange did not change (97%) when compared to CSF culture. However, both India ink and acridine orange had poor predictive values with reference to culture. Acridine orange is a better alternative to India ink in the rapid detection of cryptococcosis among CrAg positive HIV patients.


An appraisal of the process of protocol review by an ethics review conmmittee in a tertiary institution in Ibadan.
It is a well established norm that biomedical research involving human participants must conform to acceptable scientific principles and international codes of research ethics. The University of Ibadan/University College Hospital Health Research Ethics Committee (UI/UCH HREC) is the body that plays an oversight role and performs the function of a third party independent review of research protocols submitted by staff and students of the two institutions. A 6-year (2002-2007) retrospective audit of the protocols submitted to the HREC was performed to determine the profile of the lead investigator, sources of funding for the research and the duration for review using a 25 item questionnaire. A total of 752 protocols were submitted, 618 protocols (82%) were approved while 38 protocols were not approved. The principal investigators were mainly postgraduate students (67.1%) while academic staff constituted 21.3%. The average time from submission to approval was approximately 21 weeks (95% CI: 20-23 weeks). The period from submission to approval is significantly affected by the number of revision required and the funding agent (p < 0.05); it took a shorter time to review internationally funded research.


Emotional Aspects of Pediatric Post-Intensive Care Syndrome Following Traumatic Brain Injury.
Children with traumatic brain injury (TBI) requiring neurocritical care are at risk for neurocognitive, emotional, physical, and psychosocial difficulties, collectively known as Post-Intensive Care Syndrome. Our study assessed parent-reported emotional functioning and identified risk factors for emotional sequelae in the acute recovery phase. Fifty-three children between 5 and 18 years old hospitalized for TBI were assessed 1-month following discharge. Relevant injury-, child-, and family-specific variables were collected. Emotional functioning was assessed using PROMIS Parent Proxy Report Short Forms for Anxiety and Depressive Symptoms. We used Chi-square tests to evaluate differences between children with and without elevations in anxiety and depressive symptoms. Logistic regression determined predictors of elevations in symptoms among significant variables. Parents frequently endorsed moderate or worse anxiety (45.2%) and depressive (32.1%) symptoms among children. Mechanism of injury and elevated parent post-traumatic stress disorder (PTSD) symptoms were associated with elevated anxiety and depressive symptoms, while direct family involvement in the accident/injury was associated only with elevated anxiety symptoms. Results from logistic regression indicated that only elevated parent PTSD symptoms were a significant predictor for child anxiety and depressive symptoms. Anxiety and depressive symptoms are prevalent in the acute recovery phase of TBI. Consistent with previous research, elevations in anxiety and depressive symptoms were more related to psychosocial factors than injury severity. High levels of parent PTSD symptoms and their relationship with children's internalizing symptoms highlight the need for mental health treatment for TBI patients and their families.


The molecular biology of parasporal crystal body formation in Bacillus thuringiensis.
Data obtained using several experimental methods (curing, transconjugation, cloning, and hybridization) indicate that crystal protein genes in many subspecies of BT that are toxic to lepidopterans are located on one or more large plasmids; in some subspecies, the gene may be located on the chromosome. Detailed mapping has shown that in three plasmids (each from a different strain) the genes are surrounded by multiple copies of two repeated DNA elements; the arrangement of these elements is the same in the three plasmids. An analysis of the sequence of one of these repeated DNAs strongly suggests that it contains a transposase. Thus, transfer of crystal protein genes between plasmids and/or between plasmids and the chromosome would be possible either by transposition or by recombinational events mediated by the repeated DNAs. Crystal protein genes have been cloned from several plasmids and were expressed in E. coli and B. subtilis, whereas two genes cloned from chromosomal preparations were not expressed. Some of the factors that regulate expression of a plasmid-borne gene in E. coli and B. subtilis have been identified. Very little is known about the role of sporulation genes in regulating expression of the crystal protein gene in B. subtilis or BT. In BT, expression may also be affected by genes on other plasmids. Three homologous crystal protein genes have been identified and cloned from subsp. kurstaki and thuringiensis; different strains of these subspecies may contain one, two, or three of these genes. It seems probable that additional gene families will be found, since the crystals of different subspecies contain immunologically distinguishable proteins. The DNA sequences of the three homologous genes have been published as has the sequence of the crystal protein gene from subsp. sotto. These four genes have regions of identity (the promoter region) and similarity (the N-terminal approximately 280 amino acids, the C-terminal half of the protein, and the terminator). It is interesting that the divergent portions of the molecules are not in precisely the same positions and that all overlap the toxin-encoding portion of the gene. It would be worthwhile to determine if the differences in the amino acid sequence are related to differences in the toxicity and/or the host range of the cloned genes, and to establish how the complement of genes in a given strain contributes to the overall toxicity of that strain.(ABSTRACT TRUNCATED AT 400 WORDS)


Maternal deaths at Harare Maternity Hospital during 1983.
There were 51 maternal deaths at Harare Maternity Hospital, Zimbabwe, during 1983, 25 among patients from the greater Harare area and 26 among patients referred from peripheral hospitals or clinics. The overall maternal mortality rate among patients within the greater Harare area was 56/100 000 (including deaths related to abortion). Among 'booked' patients the maternal mortality rate was 29/100 000. Puerperal sepsis, haemorrhage, post-abortal sepsis and hypertensive disease accounted for 78.4% of the deaths. Avoidable factors, considered to be present in 34 cases (66.7%), are discussed.


Chest-tube thoracostomy causing Horner's syndrome.
Horner's syndrome developing early after lung biopsy is reported in a 42-year-old woman. At the end of the procedure a thoracostomy tube was inserted with its tip at the T1-2 posterior intercostal space. The authors conclude that direct injury to the second order preganglionic neuron in the vicinity of the stellate ganglion caused the Horner's syndrome. They recommend placing the tip of the thoracostomy tube below the level of the second rib posteriorly to prevent this complication.


Efficient Prevention of Marine Biofilm Formation Employing a Surface-Grafted Repellent Marine Peptide.
Creation of surfaces resistant to the formation of microbial biofilms via biomimicry has been heralded as a promising strategy to protect a range of different materials ranging from boat hulls to medical devices and surgical instruments. In our current study, we describe the successful transfer of a highly effective natural marine biofilm inhibitor to the 2D surface format. A series of cyclic peptides inspired by the natural equinatoxin II protein produced by Beadlet anemone (Actinia equine) have been evaluated for their ability to inhibit the formation of a mixed marine microbial consortium on polyamide reverse osmosis membranes. In solution, the peptides are shown to effectively inhibit settlement and biofilm formation in a nontoxic manner down to 1 nM concentrations. In addition, our study also illustrates how the peptides can be applied to disperse already established biofilms. Attachment of a hydrophobic palmitic acid tail generates a peptide suited for strong noncovalent surface interactions and allows the generation of stable noncovalent coatings. These adsorbed peptides remain attached to the surface at significant shear stress and also remain active, effectively preventing the biofilm formation over 24 h. Finally, the covalent attachment of the peptides to an acrylate surface was also evaluated and the prepared coatings display a remarkable ability to prevent surface colonization at surface loadings of 55 ng/cm2 over 48 h. The ability to retain the nontoxic antibiofilm activity, documented in solution, in the covalent 2D-format is unprecedented, and this natural peptide motif displays high potential in several material application areas.


Ginsenoside-Rb1 Protects Hypoxic- and Ischemic-Damaged Cardiomyocytes by Regulating Expression of miRNAs.
Ginsenoside (GS-Rb1) is one of the most important active compounds of ginseng, with extensive evidence of its cardioprotective properties. However, the miRNA mediated mechanism of GS-Rb1 on cardiomyocytes remains unclear. Here, the roles of miRNAs in cardioprotective activity of GS-Rb1 were investigated in hypoxic- and ischemic-damaged cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were first isolated, cultured, and then incubated with or without GS-Rb1 (2.5-40 μM) in vitro under conditions of hypoxia and ischemia. Cell growth, proliferation, and apoptosis were detected by MTT and flow cytometry. Expressions of various microRNAs were analyzed by real-time PCR. Compared with that of the control group, GS-Rb1 significantly decreased cell death in a dose-dependent manner and expressions of mir-1, mir-29a, and mir-208 obviously increased in the experimental model groups. In contrast, expressions of mir-21 and mir-320 were significantly downregulated and GS-Rb1 could reverse the differences in a certain extent. The miRNAs might be involved in the protective effect of GS-Rb1 on the hypoxia/ischemia injuries in cardiomyocytes. The effect might be based on the upregulation of mir-1, mir-29a, and mir-208 and downregulation of mir-21 and mir-320. This might provide us a new target to explore the novel strategy for ischemic cardioprotection.


Activity of daily living and its associated factors in war survivors with no visual acuity.
War is a known cause of tremendous physical injuries to different body organs, and eyes are not exceptions. War-related no visual acuity (NVA) affects both the victim and the family. Activity of daily living (ADL) can display personal life independency and is considered as a morbidity index. This study was designed to investigate the ADL profile of war survivors with NVA. This cross-sectional study was conducted in 2007 in Iran. In this study, 500 Iranian people with war related NVA were invited to take part in a camp in Mashhad city. ADL was evaluated using Barthel Index and demographic data were collected using a data sheet. Stepwise linear regression was used to determine the associates of ADL. The overall response rate to the invitation was 50%. From the total 250 participants 96.5% were male with a mean age of 43 ± 8 years. Only 8.3% had no dependency in ADL and other 91.7% had some ranges of dependency in at least one of the daily living activities. ADL score was higher in highly educated participants, those younger than 50 years old, those with less co-morbid physical problems (hearing loss) and those with regular physical exercises. According to regression analysis, age and duration of war related NVA were significant predictors of ADL. According to the results, both age and the time passed from war related NVA increase the dependency of people with war related NVA.


Assessment of 28-Day In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019: An International Cohort Study.
Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16-1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67-0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15-1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11-1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19-2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8-14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52-0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88-0.97; p = 0.003). This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.


A new immune-related gene signature predicts the prognosis and immune escape of bladder cancer.
The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. To elucidate the predictive value of IRGs for prognosis and immune escape in BC. We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.


Initial nipple damages in breastfeeding women: analysis of photographic images and clinical associations.
to analyze the initial nipple damage degree by breastfeeding practice and to associate findings with clinical manifestations of breastfeeding women. a retrospective, cross-sectional study with primary data and photographic images database from two randomized clinical trials. Photographic images were analyzed by two independent evaluators using the Nipple Trauma Score. For analysis, the chi-square, Mann-Whitney tests and Kappa coefficient were applied. 115 breastfeeding women and their respective 186 photographic images were analyzed. The degree of agreement of evaluators using the Nipple Trauma Score was 93.6%. The nipple pain score during breastfeeding was moderate and compromised more than 25% of the nipple surface area. assistance to breastfeeding women should prioritize nipple pain intensity instead of the nipple damage size.


Metastatic anterior chamber non-Hodgkin lymphoma in a patient with acquired immunodeficiency syndrome.
To alert ophthalmologists to the possibility of metastatic anterior chamber intraocular non-Hodgkin lymphoma in patients with acquired immunodeficiency syndrome (AIDS). We examined a 19-year-old man with AIDS who had an anterior uveitis with pseudohypopyon and a history of 2 months of malaise. A specimen of the lesion was obtained with a 25-gauge needle for pathologic examination. Systemic exploration showed hepatomegaly. Abdominal computed tomography showed multiple lesions in the liver and spleen. Fine-needle aspiration disclosed a high-grade non-Hodgkin lymphoma. The result of a fine-needle aspiration obtained from a lesion in the anterior chamber was consistent with the same diagnosis. An anterior chamber pseudohypopyon with uveitis can be the manifesting sign of a systemic lymphoma in a patient with AIDS and requires a thorough systemic evaluation.


[Efficacy and safety of ixabepilone (BMS-247550), a novel epothilone B analogue].
The epothilones are a new class of non-taxane tubulin polymerization agents obtained by natural fermentation of the myxobacteria Sorangium cellulosum. The cytotoxic activities of the epothilones, like those of the taxanes, have been linked to stabilization of microtubules, but they also have important differences. Among the epothilone family, ixabepilone (BMS247550) is a semisynthetic derivative of the natural product epothilone B. Ixabepilone was evaluated in vivo in a panel of human and rodent tumour models, the majority of which were chosen because of their known, well-characterized resistance to paclitaxel, and seems able to overcome the over-expression of multidrug resistance and to be unaffected by mutations in the beta tubulin gene. The interest of ixabepilone was clinically confirmed in clinical studies of phase II which demonstrated a strong activity at the patients with metastatic breast cancer resistant to taxanes and in patients suffering of other types of chemoresistant tumors.


Site-specific effect of thymine dimer formation on dAn.dTn tract bending and its biological implications.
dAn.dTn sequences, otherwise known as A tracts, are hotspots for cis-syn thymine dimer formation and deletion mutations induced by UV light. Such A tracts are also known to bend DNA, suggesting that some biological effects of UV light might be related to the distinctive structure and properties of cis-syn dimer-containing A tracts. To investigate the effect of thymine dimer formation on A-tract bending multimers of all possible dimer monoadducts of a dA6.dT6-containing decamer known to bend DNA were prepared along with multimers of a dimer-containing 21-mer of heterogeneous sequence. The characteristic anomalous electrophoretic behavior of the phased A-tract multimers was essentially abolished by dimer formation at the center of the A tract and was only slightly reduced by dimer formation at the ends. These effects are attributed to disruption of the A-tract structure at the site of the dimer, resulting in intact A tracts of reduced length and, hence, reduced bending. This model was suggested by the ability to formulate the estimated bend angles of the dimer-containing A tracts as approximately equal to the sum of the bend angles induced by the dimer and the remaining intact portion of the A tract. Contrary to a previous experimental study that concluded that the thymine dimer bends DNA by approximately 30 degrees, the dimer was determined to bend DNA by only approximately 7 degrees. Reduction of the bending of a DNA sequence by dimer formation may have a number of unpredicted and important biological consequences.


[Hemodynamic parameters and saturation of the cerebral cortex blood with oxygen during extracorporeal circulation in heart surgery].
Sixty-three patients were intraoperatively examined during heart surgery with extracorporeal circulation (AEC). They were operated on for an affected heart-valve apparatus (AHVA) and ischemic heart disease (IHD). There was a perioperative monitoring of central hemodynamics, pressure in the bulb of superior jugular vein (BSJV) and electroencephalography (EEG). Regional oxygenation of the brain was made in real time by a INVOS3100 oximeter (SOMANETICS, USA). A maximal saturation of the cortex blood with oxygen at AEC was registered in patients with AHVA at an average pressure below 70 mm Hg, and in patients with IHD--at 85 mm Hg. An increased pressure in BSJV at a constant mean arterial pressure and at AEC is related with blood outflow from the venous collector of the brain.


Aortoiliac operations and sexual dysfunction.
Male sexual dysfunction after aortoiliac operations can be a distressing complication. Since previous studies dealing with this problem have not excluded other causes of sexual dysfunction, the true incidence of this complication has been difficult to ascertain. We assessed preoperative and postoperative sexual function in a group of patients with no identifiable organic or functional etiology of sexual dysfunction other than aortoiliac operations or arterial occlusive disease. Seventy-six male patients had no evidence of sexual dysfunction of ambiguous etiology before or after operation. Preoperatively, 33% of patients with abdominal aortic aneurysm and 22% of those with aortoiliac occlusive disease were functionally impotent. Conventional dissection techniques rendered an additional 30% of each group functionally impotent. Postoperative impotence was twice as common in those with minor dysfunction preoperatively.


Human mesenchymal stem cells as delivery of osteoprotegerin gene: homing and therapeutic effect for osteosarcoma.
Biological treatments have been studied extensively and previous studies have proved that osteoprotegerin (OPG) can inhibit the development and progress of human osteosarcoma. However, the utility of biologic agents for cancer therapy has a short half-life, which can hardly deliver to and function in tumor sites efficiently. Mesenchymal stem cells (MSCs) have the potential to migrate to tumor sites. In this study, MSCs transfected with adenoviruses carrying the OPG gene (MSCs-OPG) were used via the tail vein to treat athymic nude mice (nu/nu) bearing osteosarcoma. In vivo and ex vivo images were used to validate the MSCs homing to tumors. The therapeutic effect for osteosarcoma was evaluated by observations on growth of tumors and bone destruction. The results showed that infected MSCs-OPG labeled with red fluorescent protein (RFP) can migrate to tumor sites and express OPG protein. The treatment by MSCs-OPG reduced the tumor growth and inhibited bone destruction in vivo. All these indicated that MSCs can deliver OPG to tumor sites, which could be a new direction of biological treatment for human osteosarcoma.


Mindfulness in Parenting and Coparenting.
Mindfulness has been established as a critical psychosocial variable for the well-being of individuals; however, less is understood regarding the role of mindfulness within the family context of parents, coparents, and children. This study tested a model examining the process by which parent dispositional mindfulness relates to parenting and coparenting relationship quality through mindful parenting and coparenting. Participants were 485 parents (59.2% mothers) from three community samples of families with youth across three developmental stages: young childhood (3 - 7 yrs.; n = 164), middle childhood (8 - 12 yrs.; n = 161), and adolescence (13 - 17 yrs.; n = 160). Path analysis using maximum likelihood estimation was employed to test primary hypotheses. The proposed model demonstrated excellent fit. Findings across all three youth development stages indicated both direct effects or parent dispositional mindfulness, as well as indirect effects through mindful parenting and mindful coparenting, with parenting and coparenting relationship quality. Implications for intervention and prevention efforts are discussed.


Systematic integration of biomedical knowledge prioritizes drugs for repurposing.
The ability to computationally predict whether a compound treats a disease would improve the economy and success rate of drug approval. This study describes Project Rephetio to systematically model drug efficacy based on 755 existing treatments. First, we constructed Hetionet (neo4j.het.io), an integrative network encoding knowledge from millions of biomedical studies. Hetionet v1.0 consists of 47,031 nodes of 11 types and 2,250,197 relationships of 24 types. Data were integrated from 29 public resources to connect compounds, diseases, genes, anatomies, pathways, biological processes, molecular functions, cellular components, pharmacologic classes, side effects, and symptoms. Next, we identified network patterns that distinguish treatments from non-treatments. Then, we predicted the probability of treatment for 209,168 compound-disease pairs (het.io/repurpose). Our predictions validated on two external sets of treatment and provided pharmacological insights on epilepsy, suggesting they will help prioritize drug repurposing candidates. This study was entirely open and received realtime feedback from 40 community members.


Cranial ossifying fibroma causing visual disorder.
Fibrous lesions of the head and the maxillofacial region are generally slow-developing benign tumors that may aggressively take course in clinical terms. These locally destructive lesions show a high recurrence rates unless they are removed gross totally. Sarcomatoid degeneration is also reported to develop in recurring lesions. Difficulties in the diagnosis, classification, and treatment make this entity complex for several years. These tumors are frequently seen among children and young adults. The maxilla and the mandibula are the 2 most common sites that the tumor originates. In our article, we discuss a 59-year-old man whose condition was diagnosed as an ossified fibroma revealing craniofacial extension. Accompanied by literature findings, it has been underlined that, as well as with the pathologic criteria, clinical features and radiologic images should be evaluated together for a specific diagnosis in fibrous lesions.


Spin crossover dynamics studies on the thermally activated molecular oxygen binding mechanism on a model copper complex.
The theoretical description of the primary dioxygen (O2) binding and activation step in many copper or iron enzymes, suffers from the intrinsically electronic non-adiabaticity of the spin flip events of the triplet dioxygen molecule (3O2), mediated by spin-orbit couplings. In this work, we presented the early-stage ultrafast spin flip dynamics of O2 binding for a simplified monocopper complex, involving the coupled singlet and triplet electronic states. The on-the-fly trajectory surface hopping (TSH) simulations have identified the dynamical effects that may influence the mode of O2 coordination (end-on vs. side-on), and the electronic structures can be viewed as complexes of molecular O2 with Cu(i) or as Cu(ii)-superoxide compounds. In addition, significant spin flip events are obversed within the sub-picosecond regime. We hope this work may provide complimentary insights on the traditional interpretation of O2 binding on copper complexes and subsequent catalytic reaction mechanisms.


Colony-forming assay of human salivary gland tumors. Applications for chemosensitivity and histogenetic studies.
Eight malignant and nine benign salivary gland neoplasms were cultured using a soft agar technique. Eleven of these tumors were successfully grown, two were contaminated, and only four demonstrated no growth. Cloning efficiency varied from 0.004% to 0.225%. These efficiencies and the 65% successful growth rate are much higher than those reported for head and neck squamous cell carcinomas. Single cell disaggregation with resultant clonal growth can be accomplished with salivary gland neoplasms. Ultrastructural study of colonies from three mixed tumors did not demonstrate distinct epithelial and mesenchymal populations of cells, the expected finding if mixed tumors were composed of two independent cell lines. Rather, mixed tumors invariably consisted of a monoclonal population of cells with evidence of ambivalent, mesenchymal, and epithelial differentiation. Myoepithelial cells were not present.


Ocular manifestations of cavernous sinus thrombosis.
A 17-year-old male presented with a 10-day history of symptoms of upper respiratory tract infection, headaches, photophobia and progressive swelling around both eyes. Clinical examination revealed a temperature of 39 °C and bilateral periorbital swelling which was worse on the left side. Initial ophthalmological examination revealed a dilated non-reactive pupil on the left side and a sluggish pupillary reflex on the right side. The patient also had a lateral rectus palsy of the left eye. Fundoscopy showed bilateral papilloedema, and visual acuity on admission was 6/12 in the right and 6/18 in the left eye. Ear, nose and throat examination revealed a rhinitic nasal mucosa with thick mucopus in the left middle meatus. The patient required surgical intervention to drain his sinuses followed by long-term intravenous antibiotic therapy and anticoagulation. After 6 weeks of therapy and close observation, he recovered with minimal sequelae.


Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands.
Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.


Intercostal and forearm muscle deoxygenation during respiratory fatigue in patients with heart failure: potential role of a respiratory muscle metaboreflex.
The purpose of this study was to determine the effect of respiratory muscle fatigue on intercostal and forearm muscle perfusion and oxygenation in patients with heart failure. Five clinically stable heart failure patients with respiratory muscle weakness (age, 66 ± 12 years; left ventricle ejection fraction, 34 ± 3%) and nine matched healthy controls underwent a respiratory muscle fatigue protocol, breathing against a fixed resistance at 60% of their maximal inspiratory pressure for as long as they could sustain the predetermined inspiratory pressure. Intercostal and forearm muscle blood volume and oxygenation were continuously monitored by near-infrared spectroscopy with transducers placed on the seventh left intercostal space and the left forearm. Data were compared by two-way ANOVA and Bonferroni correction. Respiratory fatigue occurred at 5.1 ± 1.3 min in heart failure patients and at 9.3 ± 1.4 min in controls (P<0.05), but perceived effort, changes in heart rate, and in systolic blood pressure were similar between groups (P>0.05). Respiratory fatigue in heart failure reduced intercostal and forearm muscle blood volume (P<0.05) along with decreased tissue oxygenation both in intercostal (heart failure, -2.6 ± 1.6%; controls, +1.6 ± 0.5%; P<0.05) and in forearm muscles (heart failure, -4.5 ± 0.5%; controls, +0.5 ± 0.8%; P<0.05). These results suggest that respiratory fatigue in patients with heart failure causes an oxygen demand/delivery mismatch in respiratory muscles, probably leading to a reflex reduction in peripheral limb muscle perfusion, featuring a respiratory metaboreflex.


DNp73 improves generation efficiency of human induced pluripotent stem cells.
Recent studies have found that p53 and its' associated cell cycle pathways are major inhibitors of human induced pluripotent stem (iPS) cell generation. In the same family as p53 is p73, which shares sequence similarities with p53. However, p73 also has distinct properties of its own, such as two alternative promoters to express transactivation of p73 (TAp73) and N terminal deleted p73 (DNp73). Functionally, TAp73 acts similarly to p53 in tumor suppression. However, DNp73, on the other hand acts as an oncogene to suppress p53 and p73 induced apoptosis. Therefore, how can p73 have opposing roles in human iPS cell generation? Transcription factors, Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) are used as basal conditions to generate iPS cells. In addition, the factor of DNp73(actually alpha splicing DNp73, DNp73α) is used to generate iPS cells. The experiment found that the addition of DNp73 gene increases human iPS cell generation efficiency by 12.6 folds in comparison to human fibroblast cells transduced with only the basal conditions. Also, iPS cells generated with DNp73 expression are more resistant to in vitro and in vivo differentiation. This study found DNp73, a family member of p53, is also involved in the human iPS cell generation. Specifically, that the involvement of DNp73 generates iPS cells that are more resistant to in vitro and in vivo differentiation. Therefore, this data may prove to be useful in future developmental studies and cancer researches.


Photoperiodic control of hamster testis.
The response of the testes of juvenile and adult hamsters to various photoperiods was examined. The testes of juvenile animals reached maturity regardless of the light cycle on which the animals were raised. However, the testes of adult hamsters required at least 12.5 hours of light per day to maintain spermatogenesis and prevent degeneration. This is one of the few demonstrations of a response suitable for study in investigations of the photoperiodic control of testicular function in a laboratory mammal.


The homocysteine controversy.
Mild to moderate hyperhomocysteinemia has been identified as a strong predictor of cardiovascular disease, independent from classical atherothrombotic risk factors. In the last decade, a number of large intervention trials using B vitamins have been performed and have shown no benefit of homocysteine-lowering therapy in high-risk patients. In addition, Mendelian randomization studies failed to convincingly demonstrate that a genetic polymorphism commonly associated with higher homocysteine levels (methylenetetrahydrofolate reductase 677 C>T) is a risk factor for cardiovascular disease. Together, these findings have cast doubt on the role of homocysteine in cardiovascular disease pathogenesis, and the homocysteine hypothesis has turned into a homocysteine controversy. In this review, we attempt to find solutions to this controversy. First, we explain that the Mendelian randomization analyses have limitations that preclude final conclusions. Second, several characteristics of intervention trials limit interpretation and generalizability of their results. Finally, the possibility that homocysteine lowering is in itself beneficial but is offset by adverse side effects of B vitamins on atherosclerosis deserves serious attention. As we explain, such side effects may relate to direct adverse effects of the B-vitamin regimen (in particular, the use of high-dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions.


Health and literacy in first- and second-generation Moroccan Berber women in the Netherlands: Ill literacy?
AIM: The present study was aimed at investigating the role of literacy and generation in the self-reported general health status of Moroccan Berber speaking women in the Netherlands. METHOD: Fifty women in our sample (N = 75) were first generation women, from which group 25 were literates and 25 illiterates. Another group of 25 literate women belonged to the second generation. The three groups were matched for demographic characteristics. Questionnaires were administered reflecting all concepts under study. We hypothesized that, within the first generation, illiterates compared with literates would report worse health. Our second hypothesis was that literates of the first generation compared with those of the second generation would have a similar health condition. RESULTS: After controlling for age, having a job, and having an employed partner, the first generation literates compared with the illiterates of the first generation indeed reported significantly better health. Additionally, we did not find any differences in health condition between both literate groups, even after controlling for age, number of children, and marital status. Health complaints that were most frequently reported by both groups, concerned pain in shoulders, back and head. CONCLUSIONS: Our results underline the importance of offering immigrants optimal access to opportunities and facilities that can improve their literacy and reading ability.


Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor.
The presence of mast cells near capillary sprouting sites suggests an association between mast cells and angiogenesis. However, the role of mast cells in blood vessel development remains to be defined. In an attempt to elucidate this relationship, we investigated the effect of human mast cells (HMC-1) and their products on human dermal microvascular endothelial cell (HDMEC) tube formation. Coculture of HMC-1 with HDMEC led to a dose-response increase in the network area of vascular tube growth. Moreover, the extent of neovascularization was enhanced greatly when HMC-1 were degranulated in the presence of HDMEC. Further examination using antagonists to various mast cell products revealed a blunted response (73-88% decrease) in the area of vascular tube formation if specific inhibitors of tryptase were present. Tryptase (3 microg/ml) directly added to HDMEC caused a significant augmentation of capillary growth, which was suppressed by specific tryptase inhibitors. Tryptase also directly induced cell proliferation of HDMEC in a dose-dependent fashion (2 pM-2 nM). Our results suggest that mast cells act at sites of new vessel formation by secreting tryptase, which then functions as a potent and previously unrecognized angiogenic factor.


Evaluating Barriers and Opportunities in Delivering High-Quality Oncology Care in a Resource-Limited Setting Using a Comprehensive Needs Assessment Tool.
Despite recognition of both the growing cancer burden in low- and middle-income countries and the disproportionately high mortality rates in these settings, delivery of high-quality cancer care remains a challenge. The disparities in cancer care outcomes for many geographic regions result from barriers that are likely complex and understudied. This study describes the development and use of a streamlined needs assessment questionnaire (NAQ) to understand the barriers to providing quality cancer care, identifies areas for improvement, and formulates recommendations for implementation. Using a comprehensive NAQ, in-depth interviews were conducted with 17 hospital staff involved in cancer care at two teaching hospitals in Nigeria. Data were analyzed using content analysis and organized into a framework with preset codes and emergent codes, where applicable. Data from the interviews were organized into six broad themes: staff, stuff, system, space, lack of palliative care, and provider bias, with key barriers within themes including: financial, infrastructural, lack of awareness, limited human capacity resources, lack of palliative care, and provider perspective on patient-related barriers to cancer care. Specific solutions based on ability to reasonably implement were subcategorized into short-, medium-, and long-term goals. This study provides a framework for a streamlined initial needs assessment and a unique discussion on the barriers to high-quality oncology care that are prevalent in resource-constrained settings. We report the feasibility of collecting and organizing data using a streamlined NAQ and provide a thorough and in-depth understanding of the challenges in this setting. Knowledge gained from the assessments will inform steps to improve oncology cancer in these settings.


The ELSI Virtual Forum, 30 Years of the Genome: Integrating and Applying ELSI Research.
This paper reports our analysis of the ELSI Virtual Forum: 30 Years of the Genome: Integrating and Applying ELSI Research, an online meeting of scholars focused on the ethical, legal, and social implications (ELSI) of genetics and genomics.


One-pot synthesis of 3,5-disubstituted 1,2,4-thiadiazoles from nitriles and thioamides via I2-mediated oxidative formation of an N-S bond.
A simple and practical method for I2-mediated one-pot synthesis of 3-alkyl-5-aryl-1,2,4-thiadiazoles has been developed; the one-pot reaction includes sequential intermolecular addition of thioamides to nitriles, and intramolecular oxidative coupling of N-H and S-H bonds mediated by molecular iodine. Meanwhile the protocol uses readily available nitriles and thioamides as the starting materials, molecular iodine as the oxidant, and generates various 1,2,4-thiadiazoles in moderate to good yields with a wide array of functional groups. This method is an efficient approach for the synthesis of unsymmetrically disubstituted 1,2,4-thiadiazoles.


A stopped-flow dual-wavelength spectrophotometer suitable for the study of respiratory chains.
The requirements for a dual-wavelength stopped-flow spectrophotometer to be suitable for studying limited quantities of respiratory-chain preparations are described. They can be met by a design using mainly commercially available components. The constructed apparatus has a dead-time of approx. 2.6 ms, a mixing ratio of 17:1, and a minimal requirement for 0.5 ml of mixed reactants per flow.


FACT: functional annotation transfer between proteins with similar feature architectures.
The increasing number of sequenced genomes provides the basis for exploring the genetic and functional diversity within the tree of life. Only a tiny fraction of the encoded proteins undergoes a thorough experimental characterization. For the remainder, bioinformatics annotation tools are the only means to infer their function. Exploiting significant sequence similarities to already characterized proteins, commonly taken as evidence for homology, is the prevalent method to deduce functional equivalence. Such methods fail when homologs are too diverged, or when they have assumed a different function. Finally, due to convergent evolution, functional equivalence is not necessarily linked to common ancestry. Therefore complementary approaches are required to identify functional equivalents. We present the Feature Architecture Comparison Tool http://www.cibiv.at/FACT to search for functionally equivalent proteins. FACT uses the similarity between feature architectures of two proteins, i.e., the arrangements of functional domains, secondary structure elements and compositional properties, as a proxy for their functional equivalence. A scoring function measures feature architecture similarities, which enables searching for functional equivalents in entire proteomes. Our evaluation of 9,570 EC classified enzymes revealed that FACT, using the full feature, set outperformed the existing architecture-based approaches by identifying significantly more functional equivalents as highest scoring proteins. We show that FACT can identify functional equivalents that share no significant sequence similarity. However, when the highest scoring protein of FACT is also the protein with the highest local sequence similarity, it is in 99% of the cases functionally equivalent to the query. We demonstrate the versatility of FACT by identifying a missing link in the yeast glutathione metabolism and also by searching for the human GolgA5 equivalent in Trypanosoma brucei. FACT facilitates a quick and sensitive search for functionally equivalent proteins in entire proteomes. FACT is complementary to approaches using sequence similarity to identify proteins with the same function. Thus, FACT is particularly useful when functional equivalents need to be identified in evolutionarily distant species, or when functional equivalents are not homologous. The most reliable annotation transfers, however, are achieved when feature architecture similarity and sequence similarity are jointly taken into account.


Decompressive surgery for treating nerve damage in leprosy.
Leprosy causes nerve damage which may result in nerve function impairment and disability. Decompressive surgery is used for treating nerve damage, although the effect is uncertain. This is an update of a review first published in 2009 and previously updated in 2010. To assess the effects of decompressive surgery on nerve damage in leprosy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 October 2012), CENTRAL (2012, Issue 9 in The Cochrane Library), MEDLINE (January 1966 to October 2012), EMBASE (January 1980 to October 2012), AMED (January 1985 to October 2012), CINAHL Plus (January 1937 to October 2012) and LILACS (from January 1982 to October 2012). We checked reference lists of the studies identified, the Current Controlled Trials Register (www.controlled-trials.com) (1 November 2012), conference proceedings and contacted trial authors. Randomised controlled trials (RCTs) and quasi-RCTs of decompressive surgery for nerve damage in leprosy. The primary outcome was improvement in sensory and motor nerve function after one year. Secondary outcomes were improvement in nerve function after two years, change in nerve pain and tenderness, and adverse events. Two authors independently extracted data and assessed trial quality. We contacted trial authors for additional information. We collected adverse effects information from the trials and non-randomised studies. We included two RCTs involving 88 participants. The trials were at high risk of bias. The trials examined the added benefit of surgery over prednisolone for treatment of nerve damage of less than six months duration. After two years' follow-up there was only very low quality evidence of no significant difference in nerve function improvement between participants treated with surgery plus prednisolone or with prednisolone alone. Adverse effects of decompressive surgery were not adequately described. Decompressive surgery is used for treating nerve damage in leprosy but the available evidence from RCTs is of very low quality and does not show a significant added benefit of surgery over steroid treatment alone. Well-designed RCTs are needed to establish the effectiveness of the combination of surgery and medical treatment compared to medical treatment alone.