Unintentional firearm death across the urban-rural landscape in the United States.
Unintentional injuries are one of the leading causes of death in the United States. Many of these injuries are preventable, and unintentional firearm injuries, in particular, may be responsive to prevention efforts. We investigated the relationship between unintentional firearm death and urbanicity among adults. This study was a retrospective analysis of national death certificate data. Unintentional adult firearm deaths in the United States from 1999 to 2006 were identified using the Multiple Cause of Death Data files from the National Center for Health Statistics. Decedents were assigned to a county of death and classified along an urban-rural continuum defined by population density and proximity to metropolitan areas. Total unintentional firearm death rates by county were analyzed in adjusted analyses using negative binomial regression. A total of 4,595 unintentional firearm injury deaths of adults occurred in the United States during the study period (a mean of 574.4 per year). Adjusted rates of unintentional firearm death showed increases from urban to rural counties. Americans in the most rural counties were significantly more likely to die of unintentional firearm deaths than those in the most urban counties (relative rate, 2.16; 95% confidence interval, 1.44-3.21, p = 0.002). Rates of unintentional firearm death are significantly higher in rural counties than in urban counties. Prevention strategies should be tailored to account for both geographic location and manner of firearm injury. Epidemiologic study, level III.


The gut microbiome modulates colon tumorigenesis.
Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorectal cancer, we characterized the gut microbiome in a murine model of inflammation-associated colorectal cancer that mirrors what is seen in humans. We followed the development of an abnormal microbial community structure associated with inflammation and tumorigenesis in the colon. Tumor-bearing mice showed enrichment in operational taxonomic units (OTUs) affiliated with members of the Bacteroides, Odoribacter, and Akkermansia genera and decreases in OTUs affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Conventionalization of germfree mice with microbiota from tumor-bearing mice significantly increased tumorigenesis in the colon compared to that for animals colonized with a healthy gut microbiome from untreated mice. Furthermore, at the end of the model, germfree mice colonized with microbiota from tumor-bearing mice harbored a higher relative abundance of populations associated with tumor formation in conventional animals. Manipulation of the gut microbiome with antibiotics resulted in a dramatic decrease in both the number and size of tumors. Our results demonstrate that changes in the gut microbiome associated with inflammation and tumorigenesis directly contribute to tumorigenesis and suggest that interventions affecting the composition of the microbiome may be a strategy to prevent the development of colon cancer. The trillions of bacteria that live in the gut, known collectively as the gut microbiome, are important for normal functioning of the intestine. There is now growing evidence that disruptive changes in the gut microbiome are strongly associated with the development colorectal cancer. However, how the gut microbiome changes with time during tumorigenesis and whether these changes directly contribute to disease have not been determined. We demonstrate using a mouse model of inflammation-driven colon cancer that there are dramatic, continual alterations in the microbiome during the development of tumors, which are directly responsible for tumor development. Our results suggest that interventions that target these changes in the microbiome may be an effective strategy for preventing the development of colorectal cancer.


A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC.
It is becoming increasingly apparent that many of the genes in the class III region of the human MHC encode proteins involved in the immune and inflammatory responses. Furthermore, genetic studies have indicated that genes within the class III region, particularly the telomeric segment containing the TNF gene, could contribute to susceptibility to diseases of immune-related etiology. We have sequenced an 82-kb segment of DNA around the TNF gene to identify candidate disease susceptibility genes in this region. The 10 known genes in this region have been precisely positioned with the order allograft inflammatory factor 1, G1, 1C7, leukocyte-specific transcript 1 (B144), lymphotoxin B, TNF, lymphotoxin A, NB6, IKBL, BAT1 (centromere to telomere), and their genomic structures have been defined. Comparison of the G1 genomic region with previously described cDNA and genomic sequences, together with the results of reverse transcriptase-PCR, indicates that three alternative transcripts, G1, allograft inflammatory factor 1, and IFN-gamma-responsive transcript, are all derived from this gene. The completion of the sequence of 1C7 (D6S2570) has revealed that this gene encodes a putative novel member of the Ig superfamily. A number of alternatively spliced transcripts of 1C7 were identified by reverse transcriptase-PCR, all of which are expressed in immune-related cell lines. Alternative splicing within the Ig domain-encoding region was seen to result in possible set switching between an IgV domain and an IgC2 domain. Lastly, a previously unidentified gene, homologous to a number of V-ATPase G subunits, has been located 1 kb telomeric of IKBL.


A radiographic analysis of alignment in 966 lower extremities with knee pain and its association with osteoarthritis in Indian population.
This study aimed to investigate the alignment based on deformity in knees affected by osteoarthritis (OA) at different stages and evaluate its association with OA. The following radiological parameters were measured from weight bearing long leg radiographs of 966 legs in the Indian subjects via a morphometric software (Matlab R2009a) (1)Hip-Knee-Ankle angle (HKAA), (2) Femoral bowing, (3) Tibial Bowing, (4) Condylar Plateau angle (CPA). The knees were classified according to the Kellegren and Lawrence grading and these parameters were evaluated with OA for its association using appropriate statistical tests. The mean HKAA angle was 174.5° ±6.5°, 65.8% of the limbs were in found to be in varus (<177°) and 3.8% in valgus (>183°). The mean femoral and tibial bowing was -1.19 ± 4.95° and -1.54 ± 3.58° respectively. 55.8% of femorae and 41.4% of the tibia were observed to have varus bowing while 24.12% of femorae and 12.11% the tibia were observed to have valgus bowing. An increase in odds of disease severity was observed with femoral and tibial bowing >2°. With an increase in the grades of OA a significant increase in the lateral bow of both femur and tibia was observed. The mean condylar plateau angle was observed to be -2.53° ±7.9°. Positive association was seen between the varus CPA, HKA and OA (p < 0.01). This study describes the various radiological parameters in Indian patients at different grades of OA and might elucidate the role of these factors in OA initiation and progression.


Haemostasis in normal pregnancy: a balancing act?
Pregnancy is a risk factor for venous thrombosis and the incidence of venous thromboembolism during normal pregnancy is 6-fold higher during pregnancy than in the general female population of child-bearing age. This incidence is, however, remarkably low given the increases in markers of haemostatic activation observed during normal pregnancy. During normal healthy pregnancy there are substantial changes in the haemostatic system, many of which are procoagulant and supposed to be in preparation for the haemostatic challenge of delivery. Normal haemostasis requires a balance between coagulation and fibrinolysis to maintain the integrity of the vasculature, and complex physiological changes are evident during pregnancy which appear to ensure a constant coagulation/fibrinolysis balance. This balance is maintained, at least partly, by an increase in fibrinolytic activity, but decreases in other factors such as factor XI and monocyte tissue factor expression may also serve to counterbalance procoagulant changes.


Changes in eating in dementia.
Changes in eating and weight are not uncommon in dementia although they have yet to be systematically studied. These changes are of clinical importance since they can seriously affect patients' physical health and they are often a major problem for carers. These changes are also of theoretical interest since certain abnormalities may be a direct expression of specific brain pathology. Studying these changes in eating and weight may therefore further our understanding of certain of the pathological processes underlying dementia and suggest new approaches to the management of these problems.


Genotoxic evaluation of newly synthesized iminothiazolidinones.
The current study was designed to assess the potential toxicological effects of newly synthesized iminothiazolidinones by employing Ames Salmonella, Escherichia coli WP2, Zea mays seed germination, and random amplified polymorphic DNA (RAPD) assay systems. The bacterial tester strains S. typhimurium TA1535, TA1537, TA1538, TA98, TA100, and E. coli WP2 uvrA were chosen to test the direct gene mutation inducing capabilities of the test materials in prokaryotic systems and Z. mays seeds for determination of potential toxicological effects in eukaryotic systems. OPA-3 and OPA-6 primers were used in the RAPD analysis to determine genotoxic activities on the eukaryotic genomes. According to the results, none of the test materials showed significant mutagenic activity on the bacterial tester strains at the chosen concentrations. Additionally, none of the tested compounds showed inhibition of the germination of Z. mays seeds. In contrast, the RAPD analysis results were inconsistent with the bacterial reversion assays and the seed germination assay results. All test materials significantly changed the RAPD profiles for OPA-3; however, only compound 5 showed a significant change for OPA-6 when compared with the control groups. In conclusion, the newly synthesized iminothiazolidinone derivatives (C1-C5) were determined as potentially genotoxic compounds and they should be checked with multiple toxicology test systems before further studies to determine their actual use.


Rationale and design of the familial hypercholesterolemia foundation CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia registry.
Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to 500 individuals, <10% of FH patients are formally diagnosed, and many are not appropriately treated. Contemporary data are needed to more fully characterize FH disease prevalence, treatment strategies, and patient experiences in the United States. The Familial Hypercholesterolemia Foundation (a patient-led nonprofit organization) has established the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE FH) Registry as a national, multicenter initiative to identify US FH patients, track their treatment, and clinical and patient-reported outcomes over time. The CASCADE FH will use multiple enrollment strategies to maximize identification of FH patients. Electronic health record screening of health care systems will provide an efficient mechanism to identify undiagnosed patients. A group of specialized lipid clinics will enter baseline and annual follow-up data on demographics, laboratory values, treatment, and clinical events. Patients meeting prespecified low-density lipoprotein or total cholesterol criteria suspicious for FH will have the opportunity to self-enroll in an online patient portal with information collected directly from patients semiannually. Registry patients will be provided information on cascade screening and will complete an online pedigree to assist with notification of family members. The Familial Hypercholesterolemia Foundation CASCADE FH Registry represents a novel research paradigm to address gaps in knowledge and barriers to comprehensive FH screening, identification, and treatment.


Mutations in DNA repair genes are associated with increased neo-antigen load and activated T cell infiltration in lung adenocarcinoma.
Mutations in DNA repair genes lead to increased genomic instability and mutation frequency. These mutations represent potential biomarkers for cancer immunotherapy efficacy, as high tumor mutational burden has been associated with increased neo-antigens and tumor infiltrating lymphocytes. While mismatch repair mutations have successfully predicted response to anti-PD-1 therapy in colorectal and other cancers, they have not yet been tested for lung cancer, and few have investigated genes from other DNA repair pathways. We utilized TCGA samples to comprehensively immunophenotype lung tumors and analyze the links between DNA repair mutations, neo-antigen and total mutational burden, and tumor immune infiltration. Overall, 73% of lung tumors contained infiltration by at least one T cell subset, with high mutational burden tumors containing significantly increased infiltration by activated CD4 and CD8 T cells. Further, mutations in mismatch repair genes, homologous recombination genes, or POLE accurately predicted increased tumor mutational burden, neo-antigen load, and T cell infiltration. Finally, neo-antigen load correlated with expression of M1-polarized macrophage genes, PD-1, PD-L1, IFNγ, GZMB, and FASLG, among other immune-related genes. Overall, after defining the immune infiltrate in lung tumors, we demonstrate the potential value of utilizing gene mutations from multiple DNA repair pathways as biomarkers for lung cancer immunotherapy.


Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): a reevaluation of the concept of stromal microinvasion.
Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the current diagnostic criteria for stromal microinvasion because of either qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations not meeting criteria for classic destructive invasion. This group of cases included those meeting the definition of microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features, but did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5 mo) and were covariant with other adverse prognostic features (invasive implants, nodular lymph node aggregates, high stage, and unresectable disease). Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion (ie, individual cells, cell clusters, and simple papillae). Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001), and was not associated with adverse outcome in that setting, but follow-up was limited. Based on the cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratifies patients at long-term risk for disease progression, but does not warrant a diagnosis of carcinoma or a change in current management schemes. Maintaining classification as a serous tumor of low malignant potential (serous borderline tumor) with stromal invasion seems appropriate even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher-risk lesion with a clinical course analogous to that of low-grade serous carcinoma, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until sufficient data is acquired to form more definitive conclusions regarding its prognosis.


Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools.
Protein glycosylation fundamentally impacts biological processes. Nontemplated biosynthesis introduces unparalleled complexity into glycans that needs tools to understand their roles in physiology. The era of quantitative biology is a great opportunity to unravel these roles, especially by mass spectrometry glycoproteomics. However, with high sensitivity come stringent requirements on tool specificity. Bioorthogonal metabolic labeling reagents have been fundamental to studying the cell surface glycoproteome but typically enter a range of different glycans and are thus of limited specificity. Here, we discuss the generation of metabolic 'precision tools' to study particular subtypes of the glycome. A chemical biology tactic termed bump-and-hole engineering generates mutant glycosyltransferases that specifically accommodate bioorthogonal monosaccharides as an enabling technique of glycobiology. We review the groundbreaking discoveries that have led to applying the tactic in the living cell and the implications in the context of current developments in mass spectrometry glycoproteomics.


Modelling sensory limitation: the role of tree selection, memory and information transfer in bats' roost searching strategies.
Sensory limitation plays an important role in the evolution of animal behaviour. Animals have to find objects of interest (e.g. food, shelters, predators). When sensory abilities are strongly limited, animals adjust their behaviour to maximize chances for success. Bats are nocturnal, live in complex environments, are capable of flight and must confront numerous perceptual challenges (e.g. limited sensory range, interfering clutter echoes). This makes them an excellent model for studying the role of compensating behaviours to decrease costs of finding resources. Cavity roosting bats are especially interesting because the availability of tree cavities is often limited, and their quality is vital for bats during the breeding season. From a bat's sensory point of view, cavities are difficult to detect and finding them requires time and energy. However, tree cavities are also long lasting, allowing information transfer among conspecifics. Here, we use a simple simulation model to explore the benefits of tree selection, memory and eavesdropping (compensation behaviours) to searches for tree cavities by bats with short and long perception range. Our model suggests that memory and correct discrimination of tree suitability are the basic strategies decreasing the cost of roost finding, whereas perceptual range plays a minor role in this process. Additionally, eavesdropping constitutes a buffer that reduces the costs of finding new resources (such as roosts), especially when they occur in low density. We conclude that natural selection may promote different strategies of roost finding in relation to habitat conditions and cognitive skills of animals.


Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2.
Migraine is a highly prevalent, debilitating, episodic headache disorder affecting roughly 15% of the population. Familial hemiplegic migraine type 2 (FHM2) is a rare subtype of migraine caused by mutations in the ATP1A2 gene, encoding the α2 isoform of the Na+/K+-ATPase, predominantly expressed in astrocytes. Differential comorbidities such as epilepsy and psychiatric disorders manifest in patients. Using a mouse model harboring the G301R disease-mutation in the α2 isoform, we set to unravel whether α2+/G301R mice show an increased susceptibility for epilepsy and cortical spreading depression (CSD). We performed in vivo experiments involving cortical application of KCl in awake head-restrained male and female mice of different age groups (adult and aged). Interestingly, α2+/G301R mice indeed showed an increased susceptibility to both CSD and epileptiform activity, closely replicating symptoms in FHM2 patients harboring the G301R and other FHM2-causing mutations. Additionally, this epileptiform activity was superimposed on CSDs. The age-related alteration towards CSD indicates the influence of female sex hormones on migraine pathophysiology. Therefore, the FHM2, α2+/G301R mouse model can be utilized to broaden our understanding of generalized epilepsy and comorbidity hereof in migraine, and may be utilized toward future selection of possible treatment options for migraine.


Autosomal Dominant Tubulointerstitial Kidney Disease Due to MUC1 Mutation.
Mucin 1 kidney disease, previously referred to as medullary cystic kidney disease type 1, is a rare hereditary kidney disease. It is one of several diseases now termed autosomal dominant tubulointerstitial kidney disease, as proposed by a KDIGO (Kidney Disease: Improving Global Outcomes) consensus report in 2014. Autosomal dominant tubulointerstitial kidney diseases share common clinical findings, such as autosomal dominant inheritance, bland urinary sediment, absent to mild proteinuria, and progressive loss of kidney function. Although the pathophysiology of mucin 1 kidney disease is still under investigation, genetic testing has been developed to detect the most well-known mutation, a single cytosine insertion into a string of 7 cytosines in the variable-number tandem repeat (VNTR) region of the MUC-1 gene. With this diagnostic tool, nephrologists can offer genetic counseling to affected families and monitor closely for progression of disease. We report a Hispanic patient with a strong family history of chronic kidney disease who tested positive for the MUC1 mutation.


A Systematic Review on the Health Effects of Plums (Prunus domestica and Prunus salicina).
In recent times, plums have been described as foods with health-promoting properties. Research on the health effects of plum continue to show promising results on its antiinflammatory, antioxidant and memory-improving characteristics. The increased interest in plum research has been attributed to its high phenolic content, mostly the anthocyanins, which are known to be natural antioxidants. A systematic review of literature was carried out to summarize the available evidence on the impact of plums (Prunus species; domestica and salicina) on disease risk factors and health outcomes. A number of databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for relevant studies on plum health effects in vitro, animal studies and clinical trials. A total of 73 relevant peer-reviewed journal articles were included in this review. The level of evidence remains low. Of the 25 human studies, 6 were confirmatory studies of moderate quality, while 19 were exploratory. Plums have been shown to possess antioxidant and antiallergic properties, and consumption is associated with improved cognitive function, bone health parameters and cardiovascular risk factors. Most of the human trials used the dried version of plums rather than fresh fruit, thus limiting translation to dietary messages of the positioning of plums in a healthy diet. Evidence on the health effect of plums has not been extensively studied, and the available evidence needs further confirmation. Copyright © 2016 John Wiley & Sons, Ltd.


A method for positioning the premaxilla during impression making for a patient with bilateral cleft lip and palate: a clinical report.
In patients with bilateral cleft lip and palate (BCLP), orthodontic and facial orthopedic treatments alone occasionally fail to resolve problems because of the absence of alveolar and palatal hard and soft tissue or contraction resulting from previous surgical repair. Prosthetic reconstruction of the anterior maxilla is important for these patients. Patients with BCLP have premaxillary displacement in up to 3 dimensions. It may be difficult to make impressions without deformation. This clinical report describes a method for positioning the mobile premaxilla during impression making for a patient with BCLP.


Investigating the Relationship between Insulin-like Growth Factor-1 (IGF-1) in diabetic mother's breast milk and the blood serum of their babies.
Since research investigating IGF-1 levels in breast milk are few, the goal of this study was to analyze the IGF-1 levels in the breast milk of diabetic mothers as well as in the serum of their newborn babies and to identify what relationship exists between blood serum and IGF-1 milk levels through patient measurement of mothers and their babies. This case control study was undertaken under the auspices of the Clinic of Neonatology at Al Minia University Pediatric Hospital over May 2012 through May 2013. With a total of 30 diabetic mothers and their babies forming the experimental group and the control group consisting of 15 non-diabetic mothers and their babies. A detailed medical history, anthropometric assessments, as well as the measurement of the baby's serum IGF-1 and their mother's breast milk IGF-1 levels were taken from all participants using ELSIA. The resulting data were analyzed via Statistical Package for the Social Sciences (SPSS) version 16 and measurements of descriptive statistics, t-test, Chi-square test, as well as the Pearson Correlation Coefficient. The Infants born to Diabetic Mothers (IDMs) demonstrated significantly greater anthropometric measurement. Both the serum levels and the milk IGF-1 levels as well as all of the physical measurements taken were found to have a positive correlation between the level of IGF-1 in mother's milk and all of the anthropometric measurements studied with the exception of delivered baby's length. Higher levels of IGF-1 are present in the milk of diabetic mothers and the blood serum of their babies and this characteristic could be used as a prenatal biomarker for macrosomia.


Somatic gene mutation analysis of triple negative breast cancers.
The aims of this study were to analyze triple negative breast cancer (TNBC) using an expanded next generation sequencing (NGS) assay, assess the clinical relevance using a recently described database, and correlate tumor morphology with detected genetic alterations. DNA was isolated from twenty primary TNBCs and genes of interest were enriched and sequenced with hybrid capture, followed by variant detection and functional and clinical annotation. The JAX-CTP™ assay detects actionable variants in the form of single nucleotide variations, small insertions and deletions (≤50 bp), and copy number variants in 358 genes in specimens containing a neoplastic cell content of ≥50%. The JAX-CKB is a comprehensive database that curates tumor phenotype, genetic variant and protein effect, therapeutic relevance, and available treatment options. 18/20 (90%) of TNBCs contained at least one somatic mutation detected by the JAX-CTP™. MYC amplification was the most common alteration, present in 75% of tumors. TP53, AURKA, and KDR mutations were each present in 30% (6/20) of cases. Related recruiting clinical trials, extracted from JAX-CKB, included 166 for breast cancer, of which 17 were specific to only the TNBC subtype. All 17 trials were testing at least one therapy that targets a mutation identified in this sample set. The majority (89%) of tumors with basal-like histologic features had MYC amplification. The expanded gene panel identified a variety of clinically actionable gene alterations in TNBCs. The identification of such variants increases the possibility for new therapeutic interventions and clinical trial eligibility for TNBC patients.


Structure-Kinetics Correlations in Isostructural Crystals of α-(ortho-Tolyl)-acetophenones: Pinning Down Electronic Effects Using Laser-Flash Photolysis in the Solid State.
Aqueous suspensions of nanocrystals in the 200-500 nm size range of isostructural α-(ortho-tolyl)-acetophenone (1a) and α-(ortho-tolyl)-para-methylacetophenone (1b) displayed good absorption characteristics for flash photolysis experiments in a flow system, with transient spectra and decay kinetics with a quality that is similar to that recorded in solution. In contrast to solution measurements, reactions in the solid state were characterized by a rate limiting hydrogen transfer reaction from the triplet excited state and a very short-lived biradical intermediate, which does not accumulate. Notably, the rate for δ-hydrogen atom transfer of 1a (2.7 × 10(7) s(-1)) in the crystalline phase is 18-fold larger than that of 1b (1.5 × 10(6) s(-1)). With nearly identical molecular and crystal structures, this decrease in the rate of δ-hydrogen abstraction can be assigned unambiguously to an electronic effect by the para-methyl group in 1b, which increases the contribution of the (3)π,π* configuration relative to the reactive (3)n,π* configuration in the lowest triplet excited state. These results highlight the potential of relating single crystal X-ray structural data with absolute kinetics from laser flash photolysis.


Photoacoustic and Magnetic Resonance Imaging Bimodal Contrast Agent Displaying Amplified Photoacoustic Signal.
Progress in photoacoustic (PA) and magnetic resonance imaging (MRI) bimodal contrast agents has been achieved mainly by utilizing the imaging capability of single or multiple components and consequently realizing the desired application for both imaging modalities. However, the mechanism of the mutual influence between components within a single nanoformulation, which is the key to developing high-performance multimodal contrast agents, has yet to be fully understood. Herein, by integrating conjugated polymers (CPs) with iron oxide (IO) nanoparticles using an amphiphilic polymer, a bimodal contrast agent named CP-IO is developed, displaying 45% amplified PA signal intensity as compared to bare CP nanoparticle, while the performance of MRI is not affected. Further experimental and theoretical simulation results reveal that the addition of IO nanoparticles in CP-IO nanocomposites contributes to this PA signal amplification through a synergistic effect of additional heat generation and faster heat dissipation. Besides, the feasibility of CP-IO nanocomposites acting as PA-MRI bimodal contrast agents is validated through in vivo tumor imaging using mice models. From this study, it is demonstrated that a delicately designed structural arrangement of various components in a contrast agent could potentially lead to a superior performance in the imaging capability.


IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones.
We investigated the role of IL-12 in proliferation of various Th cell clones (class II-alloreactive (4-86 and 4-55) and keyhole limpet hemocyanin + self I-Ek-reactive (9-16)) following stimulation with Ag on APCs. These clones proliferated in response to stimulation with rIL-2, rIL-12, or Ag/APC. The proliferation induced by Ag/APC stimulation was not affected by anti-IL-2 Ab but was markedly inhibited by anti-IL-12 Abs. Consistent with this finding was the absence of detectable IL-2 activity in culture supernatants 12 to 48 h after Ag/APC stimulation, and the detection of significant levels of IL-12 in an Ab-capture bioassay. IL-12 was produced within 12 h after Ag/APC stimulation, reaching a peak after 18 to 24 h. The production of IL-12 in cultures of Th clones and APC contrasted with the production of IL-2 but not IL-12 upon allostimulation of primary T cells and the inhibition of their proliferation exclusively by anti-IL-2 Abs. Analysis of the expression of IL-12-binding sites on Th cells revealed low levels of IL-12 receptors in resting Th clones but high IL-12R levels 2 to 3 days after Ag/APC stimulation, declining gradually thereafter. The changes in IL-12R expression levels correlated closely with the IL-12 responsiveness of Th populations at various times after Ag/APC stimulation; Th populations obtained 3 and 10 days after Ag/APC stimulation exhibited very high and weak or marginal responsiveness to rIL-12, respectively, whereas the responses to rIL-2 were comparable in both Th populations. These results indicate that the Ag/APC-stimulated proliferation of terminally differentiated Th clones, in contrast to naive T cells, depends on the production of IL-12 by APC and on the simultaneous up-regulation of IL-12R on Th cells rather than on an IL-2 autocrine mechanism.


Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects.
Effects on airway dynamics, heart rate, and the central nervous system of various doses of delta9-tetrahydrocannabinol administered in a random, double blind fashion using a Freon-propelled, metered-dose nebulizer were evaluated in 11 healthy men and 5 asthmatic subjects. Effects of aerosolized delta9-tetrahydrocannabinol were compared with aerosolized placebo and isoproterenol and with 20 mg of oral and smoked delta9-tetrahydrocannabinol. In the normal subjects, after 5 to 20 mg of aerosolized delta9-tetrahydrocannabinol, specific airway conductance increased immediately, reached a maximum (33 to 41 per cent increase) after 1 to 2 hours, and remained significantly greater than placebo values for 2 to 3 hours. The bronchodilator effect of aerosolized delta9-tetrahydrocannabinol was less than that of isoproterenol after 5 min, but significantly greater than that of isoproterenol after 1 to 3 hours. The magnitude of bronchodilatation after all doses of aerosolized delta9-tetrahydrocannabinol was comparable, but 5 mg of delta9-tetrahydrocannabinol caused a significantly smaller increase in heart rate and level of intoxication than the 20-mg dose. Smoked delta9-tetrahydrocannabinol produced greater cardiac and intoxicating effects than either aerosolized or oral delta9-tetrahydrocannabinol. Side effects of aerosolized delta9-tetrahydrocannabinol included slight cough and/or chest discomfort in 3 of the 11 normal subjects. Aerosolized delta9-tetrahydrocannabinol caused significant bronchodilatation in 3 of 5 asthmatic subjects, but caused moderate to severe bronchoconstriction associated with cough and chest discomfort in the other 2. These findings indicate that aerosolized delat9-tetrahydrocannabinol, although capable of causing significant bronchodilatation with minimal systemic side effects, has a local irritating effect on the airways, which may make it unsuitable for therapeutic use.


Efficient adenoviral vector transduction of human hematopoietic SCID-repopulating and long-term culture-initiating cells.
This article presents our studies on the adenoviral transduction efficiency, level of transgene expression, cell cycle status, and multilineage reconstitution ability of human CD34+ hematopoietic cells transduced under proliferating and survival growth conditions. Bone marrow and umbilical cord blood CD34+ cells were cultured in serum-free medium under survival conditions with thrombopoietin (Tpo) alone, or under proliferating conditions with Tpo, c-Kit ligand (KL), and Flt3 ligand (FL). Adenoviral vectors carrying the enhanced green fluorescent protein (EGFP) gene under the control of the PGK-1 promoter were used to transduce CD34+ cells. Approximately 10% of CD34+ cells were EGFP+ under both culture conditions. In contrast, up to 50% of CD34+CD38- cells were EGFP+, whereas a maximum of 8% of CD34+CD38(high) cells were EGFP+ (p < 0.001). Both colony-forming unit cells (CFU-C) and 5-week long-term culture-initiating cells (LTC-ICs) were efficiently transduced. Under survival conditions, a substantial fraction of transduced CD34+ cells remained quiescent. The nondividing CD34+EGFP+ cells contained LTC-ICs capable of reconstituting longterm culture for as long as 10 weeks. CD34+EGFP+ cells also retained the ability to engraft and multilineage-reconstitute NOD/SCID mice. These observations demonstrate that primitive human hematopoietic progenitor cells can be efficiently transduced by adenoviral vectors.


The monoplace hyperbaric chamber and management of decompression illness.
Three cases of decompression illness are reported. Two patients presented with joint pain and skin signs, while one patient presented with joint pain and neurological signs and symptoms. The patients received emergency recompression therapy in a Hong Kong clinic, using a monoplace hyperbaric chamber. All three patients were treated successfully and no residual signs or symptoms were evident on review at 90 days' post-treatment. Issues concerning the use of monoplace and multiplace hyperbaric chambers are also discussed, along with additional clinical applications of the monoplace hyperbaric chamber.


Bilateral sphenopalatine ganglion block reduces blood pressure in never treated patients with essential hypertension. A randomized controlled single-blinded study.
Sympathetic fibers connect sphenopalatine ganglion (SPG) with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension. We performed bilateral SPG block with lidocaine 2% in 33 hypertensive patients (mean age 48±12years, 24 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51±12years, 8 men). All patients have been subjected to 24h ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24h SBP decrease ≥5mmHg. We found that 24h and daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding BP were found in the sham operation group. SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure.


Electrochemistry of Sputtered Hematite Photoanodes: A Comparison of Metallic DC versus Reactive RF Sputtering.
The water splitting activity of hematite is sensitive to the film processing parameters due to limiting factors such as a short hole diffusion length, slow oxygen evolution kinetics, and poor light absorptivity. In this work, we use direct current (DC) magnetron sputtering as a fast and cost-effective route to deposit metallic iron thin films, which are annealed in air to obtain well-adhering hematite thin films on F:SnO2-coated glass substrates. These films are compared to annealed hematite films, which are deposited by reactive radio frequency (RF) magnetron sputtering, which is usually used for depositing metal oxide thin films, but displays an order of magnitude lower deposition rate. We find that DC sputtered films have much higher photoelectrochemical activity than reactive RF sputtered films. We show that this is related to differences in the morphology and surface composition of the films as a result of the different processing parameters. This in turn results in faster oxygen evolution kinetics and lower surface and bulk recombination effects. Thus, fabricating hematite thin films by fast and cost-efficient metallic iron deposition using DC magnetron sputtering is shown to be a valid and industrially relevant route for hematite photoanode fabrication.


[Introduction to Research Electronic Data Capture (REDCap) and REDCap2SDTM, a Conversion Tool to Facilitate Clinical Research Data Sharing].
Clinical Data Interchange Standards Consortium (CDISC), Study Data Tabulation Model (SDTM) is used in new drug application studies and for sharing and reuse of accumulated clinical research data. Clinical trial manuscripts submitted to International Committee of Medical Journal Editors member journals are required to contain a statement on data sharing. We introduce here Research Electronic Data Capture (REDCap) and REDCap2SDTM, a tool for converting research data to CDISC SDTM for facilitating data sharing. This tool will help reduce the workload in new drug application studies and allow the effective reuse of clinical research data.


ACCCN national nursing workforce survey of intensive care units.
A descriptive study was designed and implemented by the Australian College of Critical Care Nurses (ACCCN) Workforce Planning Advisory Committee to capture data pertaining to workforce issues of intensive care nurses. All intensive care units (ICUs) within Australia were mailed a self reporting survey. Despite a low response rate (52 per cent) and difficulty reported by respondents in gaining the appropriate data requested, the results revealed an interesting snapshot of the intensive care nursing workforce. Types of services offered by units varied considerably; paid overtime hours were low (< 2 per cent of total hours worked) and use of both part-time and agency staff was also low (10 per cent of total hours worked). Private hospitals utilised a greater proportion of part-time and agency nursing staff than public hospitals (20:10 per cent). The turnover rate for registered nursing staff was estimated at 18 per cent, with education, skill acquisition and improved communication reported as the major incentives used by managers to attract and retain staff. This study demonstrated that valuable data are currently uncaptured and recommends a more refined process of a national database to record and manage this important information for future workforce planning.


Mazzanema n. gen. and Mazzanema fortuita n. comb. for Longistriata fortuita Freitas, Lent, and Almeida, 1937 (Nematoda: Heligmonellidae), a parasite of the marsh rat Holochilus chacarius (Rodentia: Cricetidae) from northern Argentina.
The species described as Longistriata fortuita Freitas, Lent, and Almeida, 1937 is here redescribed from new material collected from the type host, Holochilus chacarius balnearum Thomas, and the type locality, San Martín del Tabacal, Salta, Argentina. Neotypes are designed for the species since the type material deposited by the authors is lost. The original description did not include the synlophe or the female and both are here described. Several characters of the synlophe as the number of ridges (14-19), the ridges continuous and all around body, and the presence of a gradient of size of the ridges allow us to place the species within the Heligmonellidae, Nippostrongylinae. The species possesses a unique combination of characters as the synlophe having a carene together with characters of the caudal bursa as the pattern 1-3-1 and the strong development of the dorsal lobe and ray, which precludes its inclusion in any known genus of Nippostrongylinae. A new genus Mazzanema n. gen. is proposed for it, resulting in the new combination Mazzzanema fortuita n. comb.


Detection of innocent systolic murmurs by auscultation and their relation to hematologic and echocardiographic findings in clinically normal Whippets.
To determine murmur prevalence by auscultation of 105 apparently healthy Whippets without signs of cardiac disease, to determine the origin of these murmurs, and to evaluate the influence of sex, type of pedigree (ie, bred for showing or racing), and training on these murmurs. Cross-sectional study. 105 client-owned Whippets. All dogs were auscultated by the first author and underwent a complete physical and cardiological examination, together with a hematologic assessment. Several RBC variables and echocardiographic variables were compared between dogs with or without a murmur at the level of the aortic valve. 44 of 105 (41.9%) dogs had no murmur. A soft systolic murmur was present with point of maximal intensity at the level of the aortic valve in 50 (47.6%) dogs, at the level of the pulmonic valve in 8 (7.6%) dogs, and at the level of the mitral valve in 3 (2.9%) dogs. No significant differences were found in heart rate, rhythm, murmur presence, point of maximal intensity, and murmur grade between males and females, between dogs with race- and show-type pedigrees, or between dogs in training and not in training. Dogs with a murmur at the level of the aortic valve had a significantly higher aortic and pulmonic blood flow velocity and cardiac output, compared with dogs without a murmur. Whippets have a high prevalence of soft systolic murmurs in the absence of any structural abnormalities, which fit the description of innocent murmurs. No influence of sex, pedigree type, or training was found on the occurrence of these murmurs in Whippets.


The effect of lumbar epidural anesthesia on maternal middle cerebral artery blood flow in normal pregnancy: a prospective, randomized, double-blind comparison study.
Lumbar epidural anesthesia is associated with a transient elevation in intracranial pressure in both animals and humans and decreased cerebral blood flow in animals. We sought to determine the effect of medium-onset and slow-onset local anesthetic lumbar epidural anesthesia on maternal cerebral blood flow in normal human pregnancy. In an Institutional Review Board-approved, double-blind study, 24 healthy, normotensive, nonlaboring, term gravida women undergoing elective cesarean section were prospectively placed into random groups to receive either 2% lidocaine with 8.4% sodium bicarbonate (1:10) or 0.5% bupivacaine lumbar epidural anesthesia. After prehydration with 20 mL/kg crystalloid and 15-degree left-wedged supine positioning with 15-degree head tilt, transcranial Doppler ultrasound (Nicolet Pioneer EME) and simultaneous electrocardiogram, automatic blood pressure (Dinamap), and end-tidal CO2 (SAR-Trans) monitoring were performed. Pulse, blood pressure, respiratory rate, end-tidal CO2, middle cerebral artery blood flow velocity, and pulsatility index were measured at (1) baseline (once supine positioning was assumed); (2) immediately after administration of 20 mL local anesthetic; and (3) every 5 minutes for 25 minutes. Timing of the attainment of a T4 dermatome anesthetic level was noted. Comparisons were made by t test, rank sum tests, chi2, and repeated measures analysis of variance. P <.05 was considered significant. Maternal heart rate, blood pressure, respiratory rate, and end-tidal CO2 were not significantly different within or between groups. No significant difference was found in baseline middle cerebral artery blood flow velocity or pulsatility index values between groups. Neither middle cerebral artery blood flow velocity nor pulsatility index changed significantly within or between groups up to 25 minutes after institution of epidural anesthesia. Maternal middle cerebral artery blood flow velocity, as measured by transcranial Doppler ultrasonography, is maintained in normotensive, nonlaboring term gravida women receiving either lidocaine or bupivacaine lumbar epidural anesthesia, which supports intact cerebrovascular autoregulation in normal pregnancy.


Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.
The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.


Kinetic and e.p.r. studies of cyanide and azide binding to the copper sites of dopamine (3,4-dihydroxyphenethylamine) beta-mono-oxygenase.
The kinetics of inhibition of dopamine (3,4-dihydroxyphenethylamine) beta-mono-oxygenase by cyanide (CN-) and azide (N3-) ions have been investigated by using steady-state methods. Both anions show complex non-competitive-inhibition patterns with respect to ascorbate, suggestive of anion binding at two different sites on the oxidized enzyme. To further investigate this finding, e.p.r. titrations of CN- and N3- binding to the 63Cu-reconstituted enzyme were carried out. Addition of approx. 2 equiv. of CN- to copper elicits a new signal with g = 2.217, g = 2.025, A = 17.0 mT characteristic of a copper (II)-cyano complex. Simulations show that this signal accounts for half the copper (II) in the enzyme. The remainder of the enzyme-bound copper is expressed by a signal close to, but not identical with, that of native enzyme. Further addition of CN- induces a simultaneous decrease in intensity of both of these signals so that their 1:1 ratio is maintained. Binding of N3-, on the other hand, changes the e.p.r. spectrum to a form different from either that of the native or CN- -treated enzyme, and integrates to 100% of the copper in the enzyme (g = 2.252, g = 2.050, A = 16.5 mT). Resolved superhyperfine structure is apparent in the g region. N3- binding is also accompanied by the appearance of a broad charge-transfer band centred at 387 nm. Neither 9 nor 35 GHz e.p.r. spectra show evidence for more than one (non-interacting) species of Cu(II) in native enzyme and N3- derivatives. The binding and reactivity of CN-, on the other hand, argues against independent copper sites in the enzyme.


Increasing incidence of celiac disease in a North American population.
The prevalence of celiac disease (CD) varies greatly, potentially because of incomplete ascertainment of cases and small study samples with limited statistical power. Previous reports indicate that the incidence of CD is increasing. We examined the prevalence of CD in a well-defined US county. Population-based study in Olmsted County, Minnesota, USA. Using the infrastructure of the Rochester Epidemiology Project, medical, histopathology, and CD serology records were used to identify all new cases of CD in Olmsted County since 2000. Age- and sex-specific and adjusted (to the US white 2000 population) incidence rates for CD were estimated. Clinical presentation at diagnosis was also assessed. Between 2000 and 2010, 249 individuals (157 female or 63%, median age 37.9 years) were diagnosed with CD in Olmsted County. The overall age- and sex-adjusted incidence of CD in the study period was 17.4 (95% confidence interval (CI)=15.2-19.6) per 100,000 person-years, increasing from 11.1 (95% CI=6.8-15.5) in 2000-2001 to 17.3 (95% CI=13.3-21.3) in 2008-2010. The temporal trend in incidence rates was modeled as a two-slope pattern, with the incidence leveling off after 2004. Based on the two classic CD symptoms of diarrhea and weight loss, the relative frequency of classical CD among incident cases decreased over time between 2000 and 2010 (P=0.044). The incidence of CD has continued to increase in the past decade in a North-American population.


Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10(-5), odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.


About the Foreskin: Parents' Perceptions and Misconceptions.
To determine parents' understanding of the foreskin, in an effort to improve parent education. A questionnaire was administered to parents of patients attending outpatient clinics at the Wendy Fitzwilliam Paediatric Hospital (Eric Williams Medical Sciences Complex), the San Fernando General Hospital and the Scarborough General Hospital during an eight-month period. It comprised 15 questions, 10 of which asked about the role of the foreskin, retraction and views on circumcision. There were 520 completed questionnaires. The majority of participants were mothers. Twelve per cent of parents had a child who was circumcised. The reasons for circumcision were mostly because of phimosis (31%), religious reasons (26% Islamic), personal reference (21%) and infection (20%). Regarding the need for circumcision, 31% of parents believed all boys should be circumcised and 36% did not agree. The majority of parents felt that by one year, full retraction should occur and 66% of parents felt that circumcision should be performed if the foreskin is not retractable. With respect to hygiene, 75% felt that circumcision made cleaning the penis easier and 43% believed the foreskin causes infections. Concerning HIV/AIDS, 67% did not believe that circumcision helps to prevent its transmission. When considering penile cancer and sexual function, more than 50% of parents did not know the role of the foreskin. Approximately 25% of parents answered 'do not know' to most of the questions. Despite foreskin pathology being a common paediatric problem, it is clear that there is a lot of misunderstanding and ignorance of the facts relating to the function of the foreskin in children. There is an obvious need for better parent education.


A Rubisco-binding protein is required for normal pyrenoid number and starch sheath morphology in Chlamydomonas reinhardtii.
A phase-separated, liquid-like organelle called the pyrenoid mediates CO2 fixation in the chloroplasts of nearly all eukaryotic algae. While most algae have 1 pyrenoid per chloroplast, here we describe a mutant in the model alga Chlamydomonas that has on average 10 pyrenoids per chloroplast. Characterization of the mutant leads us to propose a model where multiple pyrenoids are favored by an increase in the surface area of the starch sheath that surrounds and binds to the liquid-like pyrenoid matrix. We find that the mutant's phenotypes are due to disruption of a gene, which we call StArch Granules Abnormal 1 (SAGA1) because starch sheath granules, or plates, in mutants lacking SAGA1 are more elongated and thinner than those of wild type. SAGA1 contains a starch binding motif, suggesting that it may directly regulate starch sheath morphology. SAGA1 localizes to multiple puncta and streaks in the pyrenoid and physically interacts with the small and large subunits of the carbon-fixing enzyme Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase), a major component of the liquid-like pyrenoid matrix. Our findings suggest a biophysical mechanism by which starch sheath morphology affects pyrenoid number and CO2-concentrating mechanism function, advancing our understanding of the structure and function of this biogeochemically important organelle. More broadly, we propose that the number of phase-separated organelles can be regulated by imposing constraints on their surface area.


Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.
Rats display conditioned rejection reactions during an oral infusion of a flavor previously paired with an emetic drug; considerable evidence indicates that these rejection reactions reflect nausea. Here we report that cannabidiol, a major non-psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl homolog interfere with nausea elicited by lithium chloride and with conditioned nausea elicited by a flavor paired with lithium chloride. These results suggest that cannabinoids without psychoactive side-effects may have therapeutic value in the treatment of chemotherapy-induced nausea.


Childbirth: life event or start of a long-term difficulty? Further data from the Stoke-on-Trent controlled study of postnatal depression.
This paper reports further data from the Stoke study of postnatal depression and examines whether psychosocial characteristics and symptom profiles differ between postnatal and control depression. Two hundred and thirty-two postnatal and non-postnatal control women were screened with the Edinburgh Postnatal Depression Scale; all high scorers and a sample of low scores were interviewed with the Standardised Psychiatric Interview and modified Social Maladjustment Schedule. Depression was diagnosed using the Research Diagnostic Criteria. Postnatal but not control depression was associated with a poor relationship with the woman's own mother and greater occupational instability. Depression in control women was associated with low income, having three or more children, performing manual work and occupational dissatisfaction, but postnatal depression was not. There were no differences in the symptom profiles of the postnatal and control women nor between early and late onset postnatal depression. Depression is a common and socially disabling disorder affecting mothers of young children. Postnatal depression is more contingent on acute biopsychosocial stresses caused by the arrival of a new family member. Depression in women with older children is more closely related to longer term social adversity.


Novel design of highly [110]-oriented barium titanate nanorod array and its application in nanocomposite capacitors.
Nanocomposites in capacitors combining highly aligned one dimension ferroelectric nanowires with polymer would be more desirable for achieving higher energy density. However, the synthesis of the well-isolated ferroelectric oxide nanorod arrays with a high orientation has been rather scant, especially using glass-made substrates. In this study, a novel design that is capable of fabricating a highly [110]-oriented BaTiO3 (BT) nanorod array was proposed first, using a three-step hydrothermal reaction on glass-made substrates. The details for controlling the dispersion of the nanorod array, the orientation and the aspect ratio are also discussed. It is found that the alkaline treatment of the TiO2 (TO) nanorod array, rather than the completing transformation into sodium titanate, favors the transformation of the TO into the BT nanorod array, as well as protecting the glass-made substrate. The dispersity of the nanorod array can be controlled by the introduction of a glycol ether-deionized water mixed solvent and soluble salts. Moreover, the orientation of the nanorod arrays could be tuned by the ionic strength of the solution. This novel BT nanorod array was used as a filler in a nanocomposite capacitor, demonstrating that a large energy density (11.82 J cm-3) can be achieved even at a low applied electric field (3200 kV cm-1), which opens us a new application in nanocomposite capacitors.


Importance of healthy lifestyle factors and ideal cardiovascular health metrics for risk of heart failure in Chinese adults.
The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults. A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called 'ideal cardiovascular health metrics' (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank. A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P < 0.001 for linear trend). Compared with participants with 0-1 HLS, the multivariable-adjusted HR of those with 4-5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0-2 ICVHMs, the adjusted HR (95% CIs) of those who had 7-8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P < 0.001) than healthy lifestyle factors alone. Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.


Gender dysphoria in adolescence.
Adolescents presenting with gender-related concerns are increasingly seeking support from providers from a variety of disciplines within health care settings across the world. For those treating young people who meet the criteria for the DSM 5 diagnosis of gender dysphoria (GD), complex decisions in clinical care are common. Defining best practice with this population with respect to interventions that span mental health, physical, and surgical domains can be challenging, given a relative dearth of empirical data available; yet practice guidelines have emerged from different professional organizations which can aid with this. For this review paper, a broad literature search was performed to identify relevant studies pertaining to the care of adolescents with GD. In addition, an overview of trends in clinical practice, including shifts in conceptualization of how clinicians and patients define care that is considered affirming when working with this population, is described. This paper explores the characteristics of referral patterns to specialized clinics, provides a brief overview of gender identity development in adolescence, and then describes the phenomenology of known aetiological factors and co-occurring psychiatric issues in adolescents with GD. Additionally, clinical management considerations that detail assessment aims and common treatment interventions across disciplines will be explored.


Encephalocraniocutaneous lipomatosis.
Encephalocraniocutaneous lipomatosis (ECCL) is a sporadically occurring neurocutaneous disorder of unknown aetiology. It has repeatedly been discussed as a localised form of Proteus syndrome. In 2006, the first large series of patients was reported, and diagnostic criteria were proposed. To better define the phenotypic spectrum and natural history of ECCL and to revise diagnostic criteria. 54 patients with ECCL were reviewed. Eye anomalies (mainly choristomas) and skin lesions (non-scarring alopecia, naevus psiloliparus, subcutaneous fatty masses, nodular skin tags, aplastic scalp defects) may be unilateral or bilateral and occur in a consistent pattern. Central nervous system anomalies consist of intracranial and intraspinal lipomas, congenital abnormalities of the meninges, and putative focal vascular defects resulting in highly asymmetrical changes. About two-thirds of patients have a normal development or mild retardation only, and half of them have seizures. No correlation between the extent of central nervous system anomalies and neurological features could be established. Aortic coarctation, progressive bone cysts and jaw tumours may be associated. Revised diagnostic criteria are proposed. ECCL is considered to differ from Proteus syndrome in particular, but oculoectodermal syndrome is possibly a mild variant. Pathogenetically, mosaicism for a mutated autosomal gene involved in multiple mesenchymal tumours and vasculogenesis, with or without a second hit event, is discussed.


Crohn's disease and intestinal tuberculosis: challenging from every angle.
A woman in her 20s with a recent diagnosis of Crohn's disease (CD) affecting the ileocaecal valve was started on adalimumab, after routine tuberculosis (TB) tests were negative. Her abdominal symptoms got worse and she started presenting respiratory distress and fever. Tomography revealed a left pleural effusion, pneumonia and peritonitis with pelvic abscess. The diagnosis of disseminated TB with digestive involvement was suggested and sputum cultures were positive for Mycobacterium tuberculosis Treatment for TB was started and immunosuppressants discontinued, leading to respiratory improvement. Abdominal imaging was repeated, showing worsening signs of multisegmental ileal wall thickening, ileocaecal valve obstruction and a persistent pelvic abscess. She was then submitted to a laparoscopic ileocaecal resection for suspicion of worsening CD. Histopathology showed chronic ileocolitis compatible with CD and ganglionic tuberculosis, revealing the diagnosis of intestinal tuberculosis superimposed in CD. Recovery was uneventful.


Validity of One-Day Physical Activity Recall for Estimating Total Energy Expenditure in Elderly Residents at Long-Term Care Facilities: CLinical EValuation of Energy Requirements Study (CLEVER Study).
Malnutrition is a severe problem among elderly residents living in long-term care facilities. A simple and accurate estimation for total daily energy expenditure (TEE) is required in order to provide them with an adequate amount of food. The purpose of this study was to validate a physical activity assessment tool for estimating TEE among elderly residents. The data of 58 subjects aged 69-99 y were analyzed in this study. The one-day physical activity recall was filled out by facility staff for a typical day. TEE was measured by the doubly labeled water (DLW) method (TEEDLW), and predicted by one-day physical activity recall using the basal metabolic rate (pTEEBMR) and body weight (pTEEBW). The TEEDLW, pTEEBMR and pTEEBW were 1,129±196 kcal/d, 1,186±251 kcal/d and 1,326±236 kcal/d, respectively. In a regression model, body weight, movement means and sex explained 39.0% of the variance in the difference between pTEEBMR and TEEDLW (p<0.05). Percentage of fat mass, body weight, and Barthel Index except mobility explained 47.3% of the variance in the difference between pTEEBW and TEEDLW (p<0.05). The current results suggested that pTEEBW is not recommended to estimate TEE because the error depends on body size, and pTEEBMR was significantly correlated with TEEDLW but also included systematic errors in elderly residents. In order to improve the accuracy of the present assessment to estimate TEE, it is necessary to establish a new equation of basal metabolic rate for elderly residents and consider sex and movement means to estimate TEE.


ActivityAware: An App for Real-Time Daily Activity Level Monitoring on the Amulet Wrist-Worn Device.
Physical activity helps reduce the risk of cardiovascular disease, hypertension and obesity. The ability to monitor a person's daily activity level can inform self-management of physical activity and related interventions. For older adults with obesity, the importance of regular, physical activity is critical to reduce the risk of long-term disability. In this work, we present ActivityAware, an application on the Amulet wrist-worn device that measures daily activity levels (sedentary, moderate and vigorous) of individuals, continuously and in real-time. The app implements an activity-level detection model, continuously collects acceleration data on the Amulet, classifies the current activity level, updates the day's accumulated time spent at that activity level, logs the data for later analysis, and displays the results on the screen. We developed an activity-level detection model using a Support Vector Machine (SVM). We trained our classifiers using data from a user study, where subjects performed the following physical activities: sit, stand, lay down, walk and run. With 10-fold cross validation and leave-one-subject-out (LOSO) cross validation, we obtained preliminary results that suggest accuracies up to 98%, for n=14 subjects. Testing the ActivityAware app revealed a projected battery life of up to 4 weeks before needing to recharge. The results are promising, indicating that the app may be used for activity-level monitoring, and eventually for the development of interventions that could improve the health of individuals.


Nitric oxide and castor oil-induced diarrhea.
The effect of NG-nitro-L-arginine methyl ester (L-NAME) on castor oil-induced diarrhea was studied in control rats and those treated with isosorbide dinitrate or isosorbide-5-mononitrate. Castor oil (2 ml) produced diarrhea that lasted at least 8 h. Pretreatment of the rats with L-NAME (1-25 mg/kg i.p.) 15 min before castor oil did not block the castor oil-induced diarrhea beyond 3 h after challenge but delayed its appearance (P < .05-.001). However, diarrhea was inhibited (P < .01-.001) during the entire 8 h if rats were treated twice with L-NAME (25 mg/kg) (15 min before and 3 h after castor oil). These findings suggest that L-NAME, once administered, loses its activity 3 h after its administration. The nitric oxide synthase substrate, L-arginine (150-600 mg/kg), reversed (P < .05-.01) the inhibitory effect of L-NAME on diarrhea induced by castor oil. This effect is enantiomer-specific because D-arginine (900 mg/kg) was without an effect. These results suggest that castor oil-induced diarrhea in rats involves the L-arginine nitric oxide pathway. This is further supported by the effect of isosorbide dinitrate (0.6-120 mg/kg) and isosorbide-5-mononitrate (0.6-120 mg/kg). When administered to castor oil-treated rats, these two nitric oxide-generating agents prevented in a dose-dependent fashion (P < .01-.001) the inhibitory effect of L-NAME (25 mg/kg).


A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis.
NF-kappa B is a transcription factor that can protect from or contribute to apoptosis. Here we report identification of HSCO that binds to NF-kappa B and inhibits apoptosis. HSCO mRNA was overexpressed in 20 of 30 hepatocellular carcinomas analyzed. Overexpression of HSCO inhibited caspase 9 activation and apoptosis induced by DNA damaging agents, while it augmented apoptosis induced by TNFalpha. Like I kappa B alpha, HSCO inhibited NF-kappa B activity and abrogated p53-induced apoptosis. However, the underlying mechanism was different. HSCO is a nuclear-cytoplasmic shuttling protein, bound to RelA NF-kappa B, and HSCO sequestered it in the cytoplasm by accelerating its export from the nucleus. These results suggest that overexpression of HSCO suppresses p53-induced apoptosis by preventing nuclear localization of NF-kappa B during signaling and thus contributes to hepatocarcinogenesis.


Enhanced Acousto-Optic Diffraction Efficiency in a Symmetric SrTiO(3)/BaTiO(3)/SrTiO(3) Thin-Film Heterostructure.
Guided-wave acousto-optic Bragg diffraction and surface acoustic-wave propagation in epitaxially matched SrTiO(3)/BaTiO(3)(001)/SrTiO(3) thin-film heterostructures have been theoretically studied. The optimum electromechanical coupling and Bragg diffraction efficiency have been determined at several acoustic frequencies by means of varying the thickness of the SrTiO(3) overlayer and the BaTiO(3) waveguiding layer. A strain-controlling nonpiezoelectric SrTiO(3) overlayer upon the BaTiO(3)/SrTiO(3) structure is found to enhance the coupling coefficient (k(2)) and the diffraction efficiency significantly. A comparison of asymmetric and symmetric structures shows an increase in the diffraction efficiency from 10.5% to 43.0% and a decrease in the untuned-transducer conversion efficiency from 36 to 23 dB at an operating frequency of 1 GHz with an interaction length of 1 mm and an acoustic power of 1 mW.


Patients' expectations of the benefits and harms of treatments, screening, and tests: a systematic review.
Unrealistic patient expectations of the benefits and harms of interventions can influence decision making and may be contributing to increasing intervention uptake and health care costs. To systematically review all studies that have quantitatively assessed patients' expectations of the benefits and/or harms of any treatment, test, or screening test. A comprehensive search strategy was used in 4 databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO) up to June 2013, with no language or study type restriction. We also ran cited reference searches of included studies and contacted experts and study authors. Two researchers independently evaluated methodological quality and extracted participants' estimates of benefit and harms and authors' contemporaneous estimates. Of the 15,343 records screened, 36 articles (from 35 studies) involving a total of 27,323 patients were eligible. Fourteen studies focused on a screen, 15 on treatment, 3 a test, and 3 on treatment and screening. More studies assessed only benefit expectations (22 [63%]) than benefit and harm expectations (10 [29%]) or only harm (3 [8%]). Fifty-four outcomes (across 32 studies) assessed benefit expectations: of the 34 outcomes with overestimation data available, the majority of participants overestimated benefit for 22 (65%) of them. For 17 benefit expectation outcomes, we could not calculate the proportion of participants who overestimated or underestimated, although for 15 (88%) of these, study authors concluded that participants overestimated benefits. Expectations of harm were assessed by 27 outcomes (across 13 studies): underestimation data were available for 15 outcomes and the majority of participants underestimated harm for 10 (67%) of these. A correct estimation by at least 50% of participants only occurred for 2 outcomes about benefit expectations and 2 outcomes about harm expectations. The majority of participants overestimated intervention benefit and underestimated harm. Clinicians should discuss accurate and balanced information about intervention benefits and harms with patients, providing the opportunity to develop realistic expectations and make informed decisions.


Distribution of the main malaria vectors in Kenya.
A detailed knowledge of the distribution of the main Anopheles malaria vectors in Kenya should guide national vector control strategies. However, contemporary spatial distributions of the locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili are lacking. The methods and approaches used to assemble contemporary available data on the present distribution of the dominant malaria vectors in Kenya are presented here. Primary empirical data from published and unpublished sources were identified for the period 1990 to 2009. Details recorded for each source included the first author, year of publication, report type, survey location name, month and year of survey, the main Anopheles species reported as present and the sampling and identification methods used. Survey locations were geo-positioned using national digital place name archives and on-line geo-referencing resources. The geo-located species-presence data were displayed and described administratively, using first-level administrative units (province), and biologically, based on the predicted spatial margins of Plasmodium falciparum transmission intensity in Kenya for the year 2009. Each geo-located survey site was assigned an urban or rural classification and attributed an altitude value. A total of 498 spatially unique descriptions of Anopheles vector species across Kenya sampled between 1990 and 2009 were identified, 53% were obtained from published sources and further communications with authors. More than half (54%) of the sites surveyed were investigated since 2005. A total of 174 sites reported the presence of An. gambiae complex without identification of sibling species. Anopheles arabiensis and An. funestus were the most widely reported at 244 and 265 spatially unique sites respectively with the former showing the most ubiquitous distribution nationally. Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis were reported at sites located in all the transmission intensity classes with more reports of An. gambiae in the highest transmission intensity areas than the very low transmission areas. A contemporary, spatially defined database of the main malaria vectors in Kenya provides a baseline for future compilations of data and helps identify areas where information is currently lacking. The data collated here are published alongside this paper where it may help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling.


Brain activity and functional coupling changes associated with self-reference effect during both encoding and retrieval.
Information that is processed with reference to oneself, i.e. Self-Referential Processing (SRP), is generally associated with better remembering compared to information processed in a condition not related to oneself. This positive effect of the self on subsequent memory performance is called as Self-Reference Effect (SRE). The neural basis of SRE is still poorly understood. The main goal of the present work was thus to highlight brain changes associated with SRE in terms of activity and functional coupling and during both encoding and retrieval so as to assess the relative contribution of both processes to SRE. For this purpose, we used an fMRI event-related self-referential paradigm in 30 healthy young subjects and measured brain activity during both encoding and retrieval of self-relevant information compared to a semantic control condition. We found that SRE was associated with brain changes during the encoding phase only, including both greater activity in the medial prefrontal cortex and hippocampus, and greater functional coupling between these brain regions and the posterior cingulate cortex. These findings highlight the contribution of brain regions involved in both SRP and episodic memory and the relevance of the communication between these regions during the encoding process as the neural substrates of SRE. This is consistent with the idea that SRE reflects a positive effect of the reactivation of self-related memories on the encoding of new information in episodic memory.


Changes in the secretory acinar cells of the rat parotid gland during aging.
The secretory acinar cells of parotid glands from rats of varying ages have been examined by electron microscopy to determine what age-related changes occur in these cells. The most prominent change noted in these cells is the progressive increase in the amount of lipofuscin granules with age. Lipofuscin granules are membrane-bound structures consisting of lipids, other subcomponents, and a matrix. In addition, these cells contain lipid droplets that are not associated with any other components and tend to accumulate at the base of the cells in older rats. Also, many acinar cells in the glands of old rats contain altered secretory granules which appear to be in the process of degeneration. The accumulation of lipid and degenerating secretory granules appears to be related to the reduced level of cellular secretory activity in the glands of older rats. It is possible that these two types of inclusions contribute to the formation of lipofuscin granules. Lipofuscin and degenerating secretory granules are associated with acid phosphatase, which is demonstrated cytochemically, indicating that these granules are lysosomal structures.


Thyroid morphology in lethal non-thyroidal illness: a post-mortem study.
Non-thyroidal illness (NTI) is associated with alterations in thyroid hormone metabolism. Whether morphological changes of the thyroid gland accompany NTI is unknown. The aim of the present study was to describe thyroid morphology in patients with lethal non-thyroidal disease. In an autopsy study 267 cases have been examined. Clinical data were obtained from medical records. Subjects were patients with chronic disease (group A), intensive care patients (group B) or persons who had died suddenly without pre-existing illnesses (group C). Patients (n = 93) who did not fit into one of these categories and subjects with pre-existing thyroid disorders were excluded. Thyroid histology was assessed semi-quantitatively: grade I <25%, grade II 25--50% or grade III >75% occupation of the thyroid gland by follicles with a diameter <200 microm. Mean thyroid weight was 19.9 g in group A (n=75, age 19--96 (median 75) years, 48 males); 25.7 g in group B (n=64, age 24--93 (median 69) years, 43 males); and 26.0 g in group C (n=35, age 31--89 (median 69) years, 22 males) (P<0.0005, A vs B/C). Grade I thyroid histology was present in 6 out of 75 patients with chronic illness, in 3 out of 64 intensive care patients and in 33 out of 35 sudden-death subjects. Grade III thyroid histology occurred in 30 out of 75 chronically ill patients, in 17 out of 64 intensive care patients and in 0 out of 35 sudden-death subjects (P<0.0005, C vs A/B). NTI is associated with reduced thyroid follicular size that is accompanied by lower thyroid weight in chronically ill patients but not significantly in intensive care patients.


A Kinematic Comparison of the Judo Throw Harai-Goshi during Competitive and Non-Competitive Conditions.
The purpose of this study was to compare the kinematics of kuzushi/tsukuri (KT) phases of the harai-goshi throw under competitive and non-competitive conditions. A third degree black belt subject served as the tori (thrower) for both conditions. Two black belt participants ranked as first degree and fourth degree served as the uke (faller) for the competitive and non-competitive conditions, respectively. Two video cameras (JVC 60 Hz) and a three dimensional motion analysis system (Vicon-Peak Performance Technologies, Inc., Englewood, CO) were used to collect and analyze peak velocity for the center of mass (COM) of uke and tori and peak angular velocity of tori's trunk (TAV). Data were smoothed using a 4(th) order zero lag Butterworth filter with a cut-off frequency set by the Peak software optimization technique. All variables were normalized by time as a percentage of the KT phase. In general, the COM directional velocity patterns were similar between conditions. Uke's defensive efforts during the competitive condition created differences in timing and magnitude of peak COM and TAV velocities. During competition, tori created larger peak COM velocities onto uke which indicated greater throwing power. Peak velocities for tori's COM were larger during the non-competitive condition since uke's resistance was minimal. Findings of the competitive condition suggested that mediolateral COM movement towards tori's pulling (left) hand can be an ideal set-up movement prior to execution. Tori's TAV was also greater during the competitive condition. Two distinct TAVs were observed, a counterclockwise TAV created by tori turning their hips during the entrance of the throw and a clockwise TAV created by the shoulders turning to complete the 180 degree body turn with the simultaneous leg sweep. It is thought that the counterclockwise rotation aids in producing a pre-stretch of trunk muscles which helps to create greater trunk rotation power. Key pointsCOM directional velocity patterns were similar between conditions and were consistent with the findings from previous kinetic studies.Uke's defensive efforts during the competitive condition created differences in timing and magnitude of peak COM and TAV velocities.Mediolateral COM movement towards tori's pulling (left) hand can be an ideal set-up movement prior to execuation.It is thought that the counterclockwise rotation aids in producing a pre-stretch of trunk muscles which helps to create greater trunk rotation power.


Incidence of transient ischemic attacks in Oxfordshire, England.
The Oxfordshire Community Stroke Project is a prospective register of all new cases of stroke and transient ischemic attack (TIA) in a population of 105,000 residents of Oxfordshire, England. Between November 1, 1981, and October 31, 1986, 184 patients presented for the first time to a general practitioner or hospital with a TIA. The crude annual incidence rate was 0.35/1000, 0.42/1000 standardized to the 1981 population of England and Wales. We estimate that each year approximately 21,000 patients in England and Wales (about half of whom are greater than 70 years old) consult a doctor for the first time with a TIA. Approximately 80% of our 184 patients had TIAs in the carotid distribution; the remainder had TIAs in the vertebrobasilar distribution or TIAs of uncertain vascular distribution. The incidence of TIA increased sharply with increasing age, and the overall incidence in men was very similar to that in women (incidence ratio 1.3). However, in middle age, men were much more likely to suffer a TIA than women (odds ratio 2.6), which probably explains the marked male predominance in most hospital-based studies and treatment trials in which the elderly, and thus women, are underrepresented. This has important implications for the design and interpretation of clinical trials of treatment for TIAs.


Resource utilisation and outcomes of people with heart failure in England: a descriptive analysis of linked primary and secondary care data - the PULSE study.
Heart failure (HF) is associated with high levels of resource use and mortality, but prior UK studies have not compared outcomes by HF subtype (HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)) in large patient populations. This study investigated healthcare resource utilisation and mortality in patients with HF in England, overall and by HF subtype. This non-interventional cohort study linked data from the Clinical Practice Research Datalink database to Hospital Episode Statistics inpatient and UK Office for National Statistics mortality data. Patients with a recorded HF diagnosis (new (incident) or existing (prevalent)) based on clinical codes or measures of ejection fraction between 2015 and 2019 were included. Of 383 896 patients identified with HF, 100 224 patients (26%) had a recorded subtype: 68 780 patients with HFrEF (69%) and 31 444 patients (31%) with HFpEF. In total, 918 553 person-years (PY) were included (median follow-up: 2.1 years): 625 619 PY (68%) for unknown HF subtype, 204 862 PY (22%) for HFrEF and 88 017 PY (10%) for HFpEF. Overall, 11% of patients experienced ≥1 HF hospitalisation. After age and sex adjustment, hospitalisations for HF (HHF; including recurrent hospitalisations) and HF-related general practitioner consultations occurred at rates of approximately 80/1000 and 124/1000 PY, respectively, and were highest for patients with HFrEF and unknown subtype. Overall, all-cause and cardiovascular mortality rates were 132/1000 and 49/1000 PY, respectively. Patients with unknown subtype had the highest 1-year and 5-year mortality (20% and 48%), followed by HFrEF (8% and 35%) and HFpEF (6% and 25%). HF is associated with high levels of healthcare resource use, mortality, HHF and comorbidities. Ensuring that patients receive early and appropriate guideline-directed therapies to manage HF and associated comorbidities is likely to improve patient care and reduce the burden of HF on the English healthcare system.


A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes.
The optimal management strategy for men with newly diagnosed clinically localized prostate cancer remains a matter of debate. Numerous series have reported cancer control and quality-of-life (QoL) outcomes following treatment with radical prostatectomy (RP). Critically review published oncologic and functional outcomes after RP, and evaluate factors associated with these outcome measures. A review of the literature was performed using the Medline and Web of Sciences databases. Relevant reports published between 1980 and 2011 identified using the keywords prostate cancer, radical prostatectomy, prostate-specific antigen, biochemical recurrence, incontinence, and erectile dysfunction were reviewed and summarized. Cancer control rates following RP largely depend on the definition of treatment efficacy. While up to 40% of men have been reported to experience postoperative biochemical recurrence on long-term follow-up, death from prostate cancer has been noted in <10% of men at 15 yr after surgery in contemporary series. For men with high-risk disease, surgery affords pathologic staging, thereby facilitating the selective application of secondary therapies, and has been associated with decreased mortality risk versus radiation in retrospective series. Reported functional outcomes after surgery, particularly urinary continence and erectile dysfunction, have varied greatly to date. These assessments have been limited by nonstandardized reporting methodology. The use of robot-assisted radical prostatectomy has increased in recent years, and while follow-up is thus far short, available data do not suggest the superiority of either approach in terms of functional or oncologic outcomes. RP is associated with excellent long-term cancer control. Continued efforts to conduct prospective assessments of postoperative functional outcomes are necessary using validated QoL instruments. The importance of surgical approach will also require further study, incorporating comparative oncologic, functional, and economic data.


Effect of maternal-child home visitation on pregnancy spacing for first-time Latina mothers.
We examined the impact of a maternal-child home visitation program on birth spacing for first-time Latina mothers, focusing on adolescents and women who identified as Mexican or Puerto Rican. This was a retrospective cohort study. One thousand Latina women enrolled in the Pennsylvania Nurse-Family Partnership between January 1, 2003, and December 31, 2007, were matched to nonenrolled Latina women using propensity scores. The primary outcome was the time to second pregnancy that resulted in a live birth (interpregnancy interval). Proportional hazards models and bootstrap methods compared the time to event. Home visitation was associated with a small decrease in the risk of a short interpregnancy interval (≤ 18 months) among Latina women (hazards ratio [HR] = 0.86; 95% confidence interval [CI] = 0.75, 0.99). This effect was driven by outcomes among younger adolescent women (HR = 0.80; 95% CI = 0.65, 0.96). There was also a trend toward significance for women of Mexican heritage (HR = 0.74; 95% CI = 0.49, 1.07), although this effect might be attributed to individual agency performance. Home visitation using the Nurse-Family Partnership model had measurable effects on birth spacing in Latina women.


Hypoxia-regulated glucose transporter Glut-1 may influence chemosensitivity to some alkylating agents: results of EORTC (First Translational Award) study of the relevance of tumour hypoxia to the outcome of chemotherapy in human tumour-derived xenografts.
Tumour hypoxia confers poor prognosis in a wide range of solid tumours, due to an increased malignancy, increased likelihood of metastasis and treatment resistance. Poorly oxygenated tumours are resistant to both radiation therapy and chemotherapy. However, although the link between radiation therapy and hypoxia is well established in a range of clinical studies, evidence of its influence on chemotherapy response is lacking. In this study, a panel of human tumour-derived xenografts that have been characterised previously for in vivo response to a large series of anti-cancer agents, and have been found to show chemosensitivities that correlate strongly with the parent tumour, were used to address this issue. Immunohistochemistry was carried out on formalin-fixed, paraffin-embedded sections of xenograft samples to detect expression of the intrinsic hypoxia marker Glut-1 and adducts of the bioreductive hypoxia marker pimonidazole. Glut-1 scores correlated significantly with T/C values for CCNU sensitivity (r = 0.439, P = 0.036, n = 23) and showed a borderline significant correlation with dacarbazine T/C (r = 0.405, P = 0.076, n = 20). However, there was no correlation between both Glut-1 and pimonidazole scores and T/C obtained for the bioreductive drug mitomycin C. The use of human tumour-derived xenografts offers a potentially useful way of using archival material to determine the influence of hypoxia and other tumour-microenvironmental factors on chemosensitivity without the direct use of human subjects.


Prediction of adverse events in patients receiving rapid rituximab infusion: validation of a predictive model.
Rapid rituximab infusion was approved as treatment for non-Hodgkin lymphoma by the U.S. Food and Drug Administration in 2012, but it has been administered clinically since approval of the drug rituximab in 1997. Because of the delay between the approval of the drug and the approval of the procedure, researchers sought to discover predictors for adverse events related to rapid rituximab infusion. The current study is a retrospective cohort study using medical records from a cancer center in Singapore. The purpose of the study is to validate whether high absolute lymphocyte counts can predict the occurrence of adverse events from rapid rituximab infusion over 90-minute intervals. A total of 120 patients were selected by purposive sampling, and 394 cycles of rapid rituximab infusions were available for analysis. The authors found that high absolute lymphocyte count is highly specific in identifying patients who will not experience any adverse event from rapid rituximab infusion. However, lack of sensitivity can occur when screening potential patients for adverse events.


Optical constants of crystalline and fused quartz in the far ultraviolet.
Near-normal incidence reflectance measurements of crystal and fused quartz are reported in the 1026-1640-A interval. The reflectance spectra are extended either with known data or with extrapolations to allow a Kramers-Kronig analysis. The calculated complex index of refraction is in good agreement with the results obtained by other methods. This agreement even extends to the ir.