External validation of the US and UK kidney donor risk indices for deceased donor kidney transplant survival in the Australian and New Zealand population.
The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population. Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n = 6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1 + transplant characteristics; Model 3: Model 2 + recipient characteristics) and compared using Harrell's C-statistics for the outcomes of death-censored graft survival and overall graft survival. Both scores were strongly associated with death-censored and overall graft survival (P < 0.0001 in all models). In the KDRI-only models, discrimination of death-censored graft survival was moderately good with C-statistics of 0.63 and 0.59 for the US and UK scores, respectively. Adjusting for transplant characteristics resulted in marginal improvements of the US KDRI to 0.65 and the UK KDRI to 0.63. The addition of recipient characteristics again resulted in marginal improvements of the US KDRI to 0.70 and the UK KDRI to 0.68. Similar trends were seen for the discrimination of overall graft survival. The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.


Different G(i)-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils.
fMLP- or TNF-alpha-stimulated neutrophils produced H(2)O(2) when they adhered to fibrinogen-coated surfaces but not when they adhered to collagen I-, collagen IV-, or Matrigel-coated surfaces. In contrast, LTB4- or IL-8-stimulated neutrophils did not produce H(2)O(2) when they adhered to any of these surfaces. fMLP and TNF-alpha were much more potent than LTB4 and IL-8 in stimulating neutrophils to up-regulate and to activate their alpha(M)beta(2) integrins, as measured by the binding of specific monoclonal antibodies. Pretreatment of neutrophils with pertussis toxin completely blocked their production of H(2)O(2) on fibrinogen-coated surfaces in response to fMLP and their migration through Matrigel in response to fMLP, LTB4, and IL-8. These data show that although the fMLP, LTB4, and IL-8 receptors are coupled to pertussis toxin-sensitive Galpha proteins, they signal neutrophils to initiate qualitatively different effector functions. We propose that the qualitative differences in effector functions signaled by different chemoattractants reflect qualitative differences in using G-protein beta and/or gamma subunits or other factors by their cognate receptors.


Factor assay (VIII and IX) results in the College of American Pathologists Survey Program (1980-1982).
It has become apparent that mild factor deficiency states (i.e., Factor VIII, IX, and von Willebrand's syndrome) are frequent causes of postoperative bleeding and hemorrhagic complications following trauma. Despite their incidence, they frequently are not diagnosed or in some instances are misdiagnosed. In an attempt to improve the level of performance of factor assays, the College of American Pathologists recently has introduced factor-deficient plasmas into their proficiency testing program. Initially, plasmas deficient in Factor VIII were evaluated and more recently, plasmas deficient in Factors IX and XI were included. The results of the initial survey programs indicated a lack of precision and accuracy of Factor VIII and IX assays. Similar difficulties also were encountered with plasmas deficient in Factor XI. Extensive information also was gathered on the fundamentals of laboratory performance of factor assays. This information included data regarding preparation of the standard activity curves, source of deficient substrate plasmas, number of patient sample dilutions, etc. Also, it was evident that various thromboplastins have different degrees of sensitivity to the various deficiency states. A portion of this variability may be attributable to the choice of activator, however, it would appear that the phospholipid content of the partial thromboplastins is of equal importance.


Thoracic Deformity Correction and Changes of Vital Capacity, Forced Expiratory Volume in 1 Second, and Expiratory Flow in Adolescent Idiopathic Scoliosis Five Years or More after Posterior Spinal Fusion with Thoracoplasty.
The purpose of this study is to investigate thoracic deformity correction and pulmonary function changes in patients with adolescent idiopathic scoliosis (AIS) five years or more after undergoing posterior spinal fusion with thoracoplasty for correction of a thoracic deformity. Subjects were 57 patients with AIS who underwent posterior spinal fusion between 2004 and 2010. 24 patients who had undergone thoracoplasty at least five years earlier agreed to participate in this research. X-rays, pulmonary function tests, and thoracic cage computed tomography (CT) were performed, and the Scoliosis Research Society Outcomes Questionnaire (SRS-22) was administered. CT axial images were used at the apex of the main thoracic (MT) curve. Apical vertebral rotation was evaluated using rotation angle to the sagittal plane (RAsag). Thoracic deformities were evaluated using the rib hump index (RHi) and the posterior hemithoracic symmetry ratio (PHSr). There were no significant differences between the preoperative and the final observation forced vital capacity (FVC) or the preoperative and the final observation %FVC. The forced expiratory volume in 1 s (FEV1) and %FEV1 were significantly improved at the final observation: FEV1 (preoperative: 1.88 L, final observation: 2.05 L, p = 0.045) and %FEV1 (preoperative: 57.1%, final observation: 66.2%, p = 0.001). FEV1/FVC was also significantly improved at the final observation (preoperative: 83.0%, final observation: 86.4%, p = 0.019). The peak expiratory flow (PEF) was significantly improved at the final observation (preoperative: 3.67 L/s, final observation: 4.38 L/s, p = 0.029). On the CT assessment for thoracic deformities, there were no significant changes in RAsag or RHi. PHSr was significantly increased at the final observation compared with the preoperative period. With posterior spinal fusion in combination with thoracoplasty for AIS, although the correction of deformities was limited, the pulmonary function testing demonstrated the preservation of vital capacity (VC) and improvements in the forced expiratory volume in 1 s and expiratory flow.


Prevalence of obesity and dyslipidemia in middle-aged men and women in Tanzania, Africa: relationship with resting energy expenditure and dietary factors.
The prevalence of obesity and dyslipidemia and the mean frequency of intake of selected dietary factors were studied in 545 participants aged 46-58 y and living in three areas in Tanzania. The prevalence of obesity (body mass index of > or = 30 kg/m2) was 22.5% among women and 5.4% among men, p < 0.001. Higher rates of obesity were observed in both men and women in an urban (U) area of Dar. The prevalence of dyslipidemia [(TC-HDL-C)/HDL-C > 5] among men was higher in a pastoralists (P) population of the Maasai in Monduli (22.6%) than in Dar (9.6%) and rural (R) Handeni (7.3%, p < 0.05). The mean resting energy expenditure (REE) was higher in subjects from the rural and pastoralists populations than in urban dwellers (0.024 kcal/min/kg, p < 0.001). The three areas showed different dietary patterns with subjects from the urban area consuming coconut milk (4 d/wk, p < 0.001) and meat (2.5 d/wk, p < 0.05), more often than the rural population of Handeni which had the highest consumption of green vegetables (4.2 d/wk, p < 0.001). Participants from Monduli had the highest consumption of milk per day (1,219 mL/d, p < 0.001). A simple correlation analysis showed that body mass index (BMI) correlated positively with the frequency of intake of coconut milk, fish and meat, and negatively with REE and milk consumption. Total cholesterol (TC) was negatively correlated with the frequency of intake of green vegetables, fish and the REE, and correlated positively with meat consumption and BMI in both genders. Independent of other factors, important contributors to obesity and dyslipidemia in this population were dietary factors such as meat (p < 0.001) and fish (p < 0.05), and a lower REE (p < 0.05). These findings suggest that unhealthy diet and lower energy expenditure are important contributors to obesity and dyslipidemia in Tanzania.


Lymphadenopathy associated virus infection of a blood donor--recipient pair with acquired immunodeficiency syndrome.
A retrovirus isolated from three patients with the acquired immunodeficiency syndrome (AIDS) in the United States was morphologically and antigenically identical to lymphadenopathy associated virus isolated in France. Two of these isolates were from a blood donor-recipient pair, each of whom developed AIDS. Lymphadenopathy associated virus was isolated from the blood donor's lymphocytes 12 months after his onset of AIDS symptoms and from the blood recipient's lymphocytes 1 month after her onset of AIDS symptoms. Two isolates from the blood donor-recipient pair and an isolate from an epidemiologically unrelated homosexual man were examined by competitive radioimmunoassay to determine their antigenic relatedness to each other and to other human retroviruses. The major core proteins (p25) of the isolates were antigenically identical and all three isolates were identical to prototype lymphadenopathy associated virus isolated in France.


[Cancer pain and its influence on quality of life].
Pain is an important problem for patients with cancer, occurring in half of all cancer patients and more than 90% of patients with advanced disease. Pain related to cancer is a complex, multidimensional phenomenon composed of sensory, affective, cognitive, and behavioural components. The World Health Organization (WHO) has identified cancer pain as a major international problem and pain control has become a critical element in the comprehensive care of many cancer patients. Pain and quality of life are phenomena that share several fundamental characteristics. Pain control plays a key role in determining health-related quality of life (HRQOL). Pain, when it is ongoing and uncontrolled, has a detrimental, deteriorating effect on virtually every aspect of a patient's life. It produces anxiety and emotional distress; undermines well-being; interferes with functional capacity; and hinders the ability to fulfill familial, social, and vocational roles. With such broad-based effects, it is apparent that pain would have the effect of diminishing quality of life. In patients with moderate or severe pain, interference with sleep, daily life activities, enjoyment of life, work ability, and social interactions have been reported.


High-resolution, single-molecule measurements of biomolecular motion.
Many biologically important macromolecules undergo motions that are essential to their function. Biophysical techniques can now resolve the motions of single molecules down to the nanometer scale or even below, providing new insights into the mechanisms that drive molecular movements. This review outlines the principal approaches that have been used for high-resolution measurements of single-molecule motion, including centroid tracking, fluorescence resonance energy transfer, magnetic tweezers, atomic force microscopy, and optical traps. For each technique, the principles of operation are outlined, the capabilities and typical applications are examined, and various practical issues for implementation are considered. Extensions to these methods are also discussed, with an eye toward future application to outstanding biological problems.


Transcriptome analysis of islets from diabetes-resistant and diabetes-prone obese mice reveals novel gene regulatory networks involved in beta-cell compensation and failure.
The mechanisms underpinning beta-cell compensation for obesity-associated insulin resistance and beta-cell failure in type 2 diabetes remain poorly understood. We used a large-scale strategy to determine the time-dependent transcriptomic changes in islets of diabetes-prone db/db and diabetes-resistant ob/ob mice at 6 and 16 weeks of age. Differentially expressed genes were subjected to cluster, gene ontology, pathway and gene set enrichment analyses. A distinctive gene expression pattern was observed in 16 week db/db islets in comparison to the other groups with alterations in transcriptional regulators of islet cell identity, upregulation of glucose/lipid metabolism, and various stress response genes, and downregulation of specific amino acid transport and metabolism genes. In contrast, ob/ob islets displayed a coordinated downregulation of metabolic and stress response genes at 6 weeks of age, suggestive of a preemptive reconfiguration in these islets to lower the threshold of metabolic activation in response to increased insulin demand thereby preserving beta-cell function and preventing cellular stress. In addition, amino acid transport and metabolism genes were upregulated in ob/ob islets, suggesting an important role of glutamate metabolism in beta-cell compensation. Gene set enrichment analysis of differentially expressed genes identified the enrichment of binding motifs for transcription factors, FOXO4, NFATC1, and MAZ. siRNA-mediated knockdown of these genes in MIN6 cells altered cell death, insulin secretion, and stress gene expression. In conclusion, these data revealed novel gene regulatory networks involved in beta-cell compensation and failure. Preemptive metabolic reconfiguration in diabetes-resistant islets may dampen metabolic activation and cellular stress during obesity.


Change in meniscal strain with anterior cruciate ligament injury and after reconstruction.
Meniscal injury has been well documented in association with injury to the anterior cruciate ligament. The purpose of this study was to evaluate the effect of anterior cruciate ligament transection and reconstruction on meniscal strain. Four differential variable reluctance transducer strain gauges were placed in the medial and lateral menisci of nine cadaveric knees. Each specimen was mounted to a six-degree-of-freedom knee testing device. Testing was conducted with the knee fully extended and at 45 degrees and 90 degrees of flexion, both with and without applied axial load. At each angle of flexion, an anterior and posterior tibial load was applied. Next, the anterior cruciate ligament was transected and the testing sequence was repeated. Finally, the ligament was reconstructed using a central one-third patellar tendon graft and the testing sequence was repeated. The results demonstrated statistically significant increases in meniscal strain in ligament-transected knees compared with intact specimens. A reduction in meniscal strain to a level similar to that detected in the ligament-intact knees was observed after anterior cruciate ligament reconstruction. These results have important clinical implications regarding the potentially deleterious effect of the anterior cruciate ligament-deficient knee on meniscal strain and the potential benefit of anterior cruciate ligament reconstruction.


The potential impact of experiencing social inclusion in recreation for children with and without disabilities.
Inclusive recreation programs can have individual and community impacts for children with and without disabilities. However, studies that explore the impact of such programs on children's attitudes are mixed. The purpose of this study was to explore the perspectives of children with and without disabilities on the individual impact of an inclusive recreation program. This study adopted a generic qualitative methodology. Interviews were conducted with participants between the ages of eight and 18 enrolled in the same program and each participant was interviewed twice. Inductive thematic analysis was used to analyze results. 17 participants were recruited for this study, which included nine children without disabilities (CWODs) and eight children with disabilities (CWDs). This study revealed five themes: a) CWODs have limited exposure to people with disabilities; b) CWODs and CWDs' hopes of change; c) CWODs learned how to interact with people with disabilities; d) CWODs reported greater perceived similarity in functional ability and hobbies/interests between themselves and CWDs, and; e) CWODs become more comfortable being around people with disabilities. This study helps broaden understandings of how inclusive experiences in recreation settings impact children with and without disability.IMPLICATIONS FOR REHABILITATIONChildren without disabilities can develop more positive attitudes toward children with disabilities in affective and cognitive domains after participating in an inclusive recreation program.Incorporating inclusive language into program design and implementation may promote positive attitudes toward diversity in recreation settings.Children without disabilities would benefit from more opportunities to interact with children with disabilities in unstructured, inclusive or integrated recreation settings.


Perceived health and alcohol use in individuals with HIV and Hepatitis C who use drugs.
Individuals who use illicit drugs are at heightened risk for HIV and/or Hepatitis C Virus (HCV). Despite the medical consequences of drinking for drug-using individuals with these infections, many do drink. In other studies, how individuals perceive their health relates to their engagement in risk behaviors such as drinking. However, among drug-using individuals with HIV and HCV, whether perceived health relates to drinking is unknown. We examine the association between perceived health and drinking among drug-using individuals with HIV and/or HCV. In a large, cross-sectional study, we utilized samples of individuals with HIV (n=476), HCV (n=1145), and HIV/HCV co-infection (n=180), recruited from drug treatment centers from 2005 to 2013. In each sample, we investigated the relationship between perceived health and drinking, using ordinal logistic regressions. We present uncontrolled models as well as models controlled for demographic characteristics. Among samples of drug using individuals with HIV and with HCV, poorer perceived health was associated with risky drinking only when demographic characteristics were taken into account (Adjusted Odds Ratios: 1.32 [1.05, 1.67] and 1.16 [1.00, 1.34], respectively). In the smaller HIV/HCV co-infected sample, the association of similar magnitude was not significant (AOR=1.32 [0.90, 1.93]). Drug using patients with HIV or HCV with poor perceived health are more likely to drink heavily, which can further damage health. However, when demographics are not accounted for, these effects can be masked. Patients' reports of poor health should remind providers to assess for health risk behaviors, particularly heavy drinking.


Many Faces of Parkinson's Disease: Non-Motor Symptoms of Parkinson's Disease.
Parkinson's disease (PD) is a multi-systemic disorder that is characterized by a combination of motor and non-motor symptoms (NMS). The dopaminergic neurodegeneration of PD is involved in the genesis of NMS, but other conditions and side effects of levodopa are also associated with NMS. NMS can develop at all stage of PD and rapid eyeball movement sleep behavior disorder (RBD), constipation, depression, and olfactory dysfunction are considered prodromal signs of PD. Many NMS related with motor deficits and cognitive dysfunction. Some NMS including olfactory dysfunction, RBD and abnormal stereopsis are associated with presence of other NMS of PD. In addition, several NMS can be helpful to differentiate between idiopathic PD and other parkinsonian disorders. Early recognition and management of NMS in PD patients is important for preserving quality of life.


Human DnaJ homologs dj2 and dj3, and bag-1 are positive cochaperones of hsc70.
DnaJ is an essential cochaperone of mammalian heat shock cognate 70 (hsc70) protein. We previously found that dj2 (HSDJ/hdj-2/rdj1), rather than dj1 (hsp40/hdj-1), is a partner DnaJ for the hsc70-based chaperone system. Here, we compared the distribution of dj1, dj2, and the newly found dj3 (cpr3/DNJ3/HIRIP4/rdj2) in cultured cells. Both dj3 as well as dj2 were farnesylated and were ubiquitously expressed. In immunocytochemical and subfractionation studies, these two proteins colocalized with hsc70 under normal conditions. However, dj1 and hsc70 apparently colocalized in the nucleoli after heat shock. Simultaneous depletion of dj2 and dj3 from rabbit reticulocyte lysate markedly reduced mitochondrial import of pre-ornithine transcarbamylase and refolding of guanidine-denatured luciferase. Re-addition of either dj2 or dj3 led to recovery of these reactions. In a reconstituted system, both hsc70-dj2 and hsc70-dj3 were effective in protein refolding. Anti-apoptotic protein bag-1 further stimulated ATP hydrolysis and protein refolding by both pairs. Thus, dj2 and dj3 are the partner DnaJs of hsc70 within the cell, functionally similar and much more efficient than dj1, and bag-1 is a positive cochaperone of the hsc70-dj2 and hsc70-dj3 systems.


The role of dorsolateral and ventromedial prefrontal cortex in the processing of emotional dimensions.
The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand, these regions are also involved in cognitive processing of emotions but their contribution to emotional processing is not well-studied. In the present study, we investigated the role of these regions in three dimensions (valence, arousal and dominance) of emotional processing of stimuli via ratings of visual stimuli performed by the study participants on these dimensions. Twenty- two healthy adult participants (mean age 25.21 ± 3.84 years) were recruited and received anodal and sham transcranial direct current stimulation (tDCS) (1.5 mA, 15 min) over the dorsolateral prefrontal cortex (dlPFC) and and ventromedial prefrontal cortex (vmPFC) in three separate sessions with an at least 72-h interval. During stimulation, participants underwent an emotional task in each stimulation condition. The task included 100 visual stimuli and participants were asked to rate them with respect to valence, arousal, and dominance. Results show a significant effect of stimulation condition on different aspects of emotional processing. Specifically, anodal tDCS over the dlPFC significantly reduced valence attribution for positive pictures. In contrast, anodal tDCS over the vmPFC significantly reduced arousal ratings. Dominance ratings were not affected by the intervention. Our results suggest that the dlPFC is involved in control and regulation of valence of emotional experiences, while the vmPFC might be involved in the extinction of arousal caused by emotional stimuli. Our findings implicate dimension-specific processing of emotions by different prefrontal areas which has implications for disorders characterized by emotional disturbances such as anxiety or mood disorders.


Antisocial peer affiliation and externalizing disorders: Evidence for Gene × Environment × Development interaction.
Gene × Environment interaction contributes to externalizing disorders in childhood and adolescence, but little is known about whether such effects are long lasting or present in adulthood. We examined gene-environment interplay in the concurrent and prospective associations between antisocial peer affiliation and externalizing disorders (antisocial behavior and substance use disorders) at ages 17, 20, 24, and 29. The sample included 1,382 same-sex twin pairs participating in the Minnesota Twin Family Study. We detected a Gene × Environment interaction at age 17, such that additive genetic influences on antisocial behavior and substance use disorders were greater in the context of greater antisocial peer affiliation. This Gene × Environment interaction was not present for antisocial behavior symptoms after age 17, but it was for substance use disorder symptoms through age 29 (though effect sizes were largest at age 17). The results suggest adolescence is a critical period for the development of externalizing disorders wherein exposure to greater environmental adversity is associated with a greater expression of genetic risk. This form of Gene × Environment interaction may persist through young adulthood for substance use disorders, but it appears to be limited to adolescence for antisocial behavior.


Visible-light-mediated deuteration of silanes with deuterium oxide.
Isotopically labeled compounds are highly desirable as they can serve as both mechanistic probes in chemistry and diagnostic tools in medicinal research. Herein, we report an unprecedented visible-light-mediated metal-free deuteration of silanes using D2O as an inexpensive, readily available, and easy to handle deuterium source. A broad range of aryl- and alkyl-substituted silanes were deuterated with high deuterium incorporations and yields. Furthermore, a 100 gram-scale synthesis was demonstrated using continuous-flow micro-tubing reactors, where enhanced reaction efficiency was obtained. The photoredox-catalyzed polarity matched hydrogen atom transfer (HAT) between silanes and the thiol HAT catalyst was responsible for the efficient deuteration.


Identification of an acid-activated Cl(-) channel from human skeletal muscles.
ClC-4 gene was isolated as a putative Cl(-) channel. Due to a lack of functional expression of ClC-4, its physiological role remains unknown. We isolated a human ClC-4 clone (hClC-4sk) from human skeletal muscles and stably transfected it to Chinese hamster ovary cells. Whole cell patch-clamp studies showed that the hClC-4sk channel was activated by external acidic pH and inhibited by DIDS. It passed a strong outward Cl(-) current with a permeability sequence of I(-) > Cl(-) > F(-). The hClC-4sk has consensus sites for phosphorylation by protein kinase A (PKA); however, stimulation of PKA had no effect on the currents. hClC-4sk mRNA was expressed in excitable tissues, such as heart, brain, and skeletal muscle. These functional characteristics of hClC-4sk provide a clue to its physiological role in excitable cells.


Does the use of 50% oxygen at birth in preterm infants reduce lung injury?
Bronchopulmonary dysplasia is an inflammatory fibrotic condition produced as a consequence of injurious influences in the neonatal lung. Exposing the premature lung to high concentrations of oxygen is thought to play an important part in lung injury pathogenesis. To see if the amount of oxygen used during resuscitation at birth triggers events that lead to the subsequent lung injury and if a reduction in oxygen used leads to a reduction in lung injury. The outcomes of newborn babies less than 31 weeks gestation who were resuscitated using either 50% or 100% oxygen were examined. Eight of the babies receiving 50% oxygen required an increase in their oxygen concentration. Evidence of pulmonary inflammation was determined by quantifying interleukin 6, 1beta, and 10 and tumour necrosis factor alpha in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. There were no significant differences in any of the cytokines studied in either of the groups. Death occurred in 5/26 (19%) babies who received 100% oxygen and 4/26 (15%) babies who received 50% oxygen. Survival without bronchopulmonary dysplasia at 36 weeks postmenstrual age occurred in 14/26 (54%) and 13/26 (50%). Reducing the oxygen to 50% at resuscitation did not influence either short or long term outcomes, but a small benefit could not be excluded. There was no increase in adverse clinical outcomes in babies who received 100% oxygen.


Changes in retrograde memory following temporal lobectomy.
Extensive retrograde memory deficits have been detected in patients with temporal lobe epilepsy (TLE) and in patients who have undergone temporal lobectomy (TL). To date, no group study has used a prospective longitudinal design. We assessed memory for public and autobiographical facts and events in patients (n=15) with focal left- or right-sided TLE before and after TL using a battery of tests that covered the life span. Patients who underwent TL demonstrated material-specific memory decline in retrograde memory. Left TL was associated with a significant drop in recall of famous people's names. Patients who underwent right TL exhibited a significant decline in the recall of autobiographical events from across the life span. Our study indicates for the first time that TL is associated with a risk of mild, material-specific retrograde memory decline. Verifications with a larger sample size and other measures of remote memory are needed.


Punctuational ecological changes rather than global factors drive species diversification and the evolution of wing phenotypes in Morpho butterflies.
Assessing the relative importance of geographical and ecological drivers of evolution is paramount to understand the diversification of species and traits at the macroevolutionary scale. Here, we use an integrative approach, combining phylogenetics, biogeography, ecology and quantified phenotypes to investigate the drivers of both species and phenotypic diversification of the iconic Neotropical butterfly genus Morpho. We generated a time-calibrated phylogeny for all known species and inferred historical biogeography. We fitted models of time-dependent (accounting for rate heterogeneity across the phylogeny) and paleoenvironment-dependent diversification (accounting for global effect on the phylogeny). We used geometric morphometrics to assess variation of wing size and shape across the tree and investigated their dynamics of evolution. We found that the diversification of Morpho is best explained when considering variable diversification rates across the tree, possibly associated with lineages occupying different microhabitat conditions. First, a shift from understory to canopy was characterized by an increased speciation rate partially coupled with an increasing rate of wing shape evolution. Second, the occupation of dense bamboo thickets accompanying a major host-plant shift from dicotyledons towards monocotyledons was associated with a simultaneous diversification rate shift and an evolutionary 'jump' of wing size. Our study points to a diversification pattern driven by punctuational ecological changes instead of a global driver or biogeographic history.


Depth extraction with offset pixels.
Numerous depth extraction techniques have been proposed in the past. However, the utility of these techniques is limited as they typically require multiple imaging units, bulky platforms for computation, cannot achieve high speed and are computationally expensive. To counter the above challenges, a sensor with Offset Pixel Apertures (OPA) has been recently proposed. However, a working system for depth extraction with the OPA sensor has not been discussed. In this paper, we propose the first such system for depth extraction using the OPA sensor. We also propose a dedicated hardware implementation for the proposed system, named as the Depth Map Processor (DMP). The DMP can provide depth at 30 frames per second at 1920 × 1080 resolution with 31 disparity levels. Furthermore, the proposed DMP has low power consumption as for the aforementioned speed and resolution it only requires 290.76 mW. The proposed system makes it an ideal choice for depth extraction systems in constrained environments.


SPRY2 is an inhibitor of the ras/extracellular signal-regulated kinase pathway in melanocytes and melanoma cells with wild-type BRAF but not with the V599E mutant.
BRAF mutations result in constitutively active BRAF kinase activity and increased extracellular signal-regulated kinase (ERK) signaling and cell proliferation. Initial studies have shown that BRAF mutations occur at a high frequency in melanocytic nevi and metastatic lesions, but recent data have revealed much lower incidence of these mutations in early-stage melanoma, implying that other factors may contribute to melanoma pathogenesis in a wild-type (WT) BRAF context. To identify such contributing factors, we used microarray gene expression profiling to screen for differences in gene expression between a panel of melanocytic and melanoma cell lines with WT BRAF and a group of melanoma cell lines with the V599E BRAF mutation. We found that SPRY2, an inhibitor homologous to SPRY4, which was previously shown to suppress Ras/ERK signaling via direct binding to Raf-1, had reduced expression in WT BRAF cells. Using small interfering RNA-mediated SPRY2 knockdown, we showed that SPRY2 acts as an inhibitor of ERK signaling in melanocytes and WT BRAF melanoma cells, but not in cell lines with the V599E mutation. We also show that SPRY2 and SPRY4 directly bind WT BRAF but not the V599E and other exon 15 BRAF mutants. These data suggest that SPRY2, an inhibitor of ERK signaling, may be bypassed in melanoma cells either by down-regulation of its expression in WT BRAF cells, or by the presence of the BRAF mutation.


The role of integrative oncology in a tertiary prevention survivorship program.
Since 64% of cancer patients survive more than 5 years beyond diagnosis, oncologists are challenged to expand their focus from acute care to managing the long-term health consequences of cancer treatment and ensuring the integration of cancer prevention into their practices. This review defines the cancer prevention role of integrative oncology as a key component in survivorship programs. A narrative review consisting of the results of preclinical studies, randomized controlled trials and systematic reviews that may contribute to cancer prevention. Integrative oncology focuses on the complexities of health and proposes a multitude of approaches. Its categories are mind-body techniques, physical therapies, nutrition plus supplements, and botanicals or natural health products. Behavioral modification, through selected integrative oncology interventions may enhance cancer prevention. Opportunities exist for oncologists to promote lifestyle changes that improve patients' length and quality of life. Integrative oncology utilizes techniques for self-empowerment, individual responsibility, and lifestyle changes that could potentially reduce both cancer recurrence and second primary tumors. Education in the principles of integrative oncology and evidence-based complementary therapies is lacking. There is a need for studies on cost-utility and effectiveness of whole systems programs of integrative oncology for the tertiary prevention of cancer.


Quantitative comparison of ginsenosides and polyacetylenes in wild and cultivated American ginseng.
Quantitative comparison of seven ginsenosides in wild and cultivated American ginseng revealed that the Rg(1)/Rd ratio presented a significantly large difference between cultivated and type-I (one of the defined chemotypes) wild American ginseng, facilitating this ratio as a characteristic marker for differentiating these two groups. Similarly, the ratio (Rg(1)+Re)/Rd, and the ratio of protopanaxatriol (PPT)-type ginsenosides to protopanaxadiol (PPD)-type ginsenosides showed a large difference between these two groups. On the other hand, type-II wild samples were found to have high Rg(1)/Rb(1) and Rg(1)/Re ratios and low panaxydol/panaxynol ratio, which is entirely different from Type-I American ginseng, but is very similar to that of Asian ginseng. This not only suggests that the chemotype should be taken into consideration properly when using these parameters for differentiating American and Asian ginseng, but also indicates that type-II wild American ginseng may have distinct pharmacological activities and therapeutic effects.


Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs).
Asthma exacerbations are commonly precipitated by viral upper respiratory infections (URIs). Vitamin D insufficiency associates with susceptibility to URI in patients with asthma. Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking. To conduct a randomised controlled trial of vitamin D3 supplementation for the prevention of asthma exacerbation and URI (coprimary outcomes). 250 adults with asthma in London, UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 (n=125) or placebo (n=125) over 1 year. Secondary outcomes included asthma control test and St George's Respiratory Questionnaire scores, fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum. Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes. 206/250 participants (82%) were vitamin D insufficient at baseline. Vitamin D3 did not influence time to first severe exacerbation (adjusted HR 1.02, 95% CI 0.69 to 1.53, p=0.91) or first URI (adjusted HR 0.87, 95% CI 0.64 to 1.16, p=0.34). No clinically important effect of vitamin D3 was seen on any of the secondary outcomes listed above. The influence of vitamin D3 on coprimary outcomes was not modified by baseline vitamin D status or genotype. Bolus-dose vitamin D3 supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency. NCT00978315 (ClinicalTrials.gov).


Significant Changes in Metabolic Profiles after Intervention with Selenium and Coenzyme Q10 in an Elderly Population.
Selenium and coenzyme Q10 (SeQ10) are important for normal cellular function. Low selenium intake leads to increased cardiovascular mortality. Intervention with these substances with healthy elderly persons over a period of four years in a double-blind, randomised placebo-controlled prospective study showed reduced cardiovascular mortality, increased cardiac function, and a lower level of NT-proBNP. Therefore, we wanted to evaluate changes in biochemical pathways as a result of the intervention with SeQ10 using metabolic profiling. From a population of 443 healthy elderly individuals that were given 200 µg selenium and 200 mg coenzyme Q10, or placebo daily for four years, we selected nine males on active intervention and nine males on placebo for metabolic profiling in the main study. To confirm the results, two validation studies (study 1 n = 60 males, study 2 n = 37 males) were conducted. Principal component analyses were used on clinical and demographic data to select representative sets of samples for analysis and to divide the samples into batches for analysis. Gas chromatography time-of-flight mass spectrometry-based metabolomics was applied. The metabolite data were evaluated using univariate and multivariate approaches, mainly T-tests and orthogonal projections to latent structures (OPLS) analyses. Out of 95 identified metabolites, 19 were significantly decreased due to the intervention after 18 months of intervention. Significant changes could be seen in the pentose phosphate, the mevalonate, the beta-oxidation and the xanthine oxidase pathways. The intervention also resulted in changes in the urea cycle, and increases in the levels of the precursors to neurotransmitters of the brain. This adds information to previous published results reporting decreased oxidative stress and inflammation. This is the first-time metabolic profiling has been applied to elucidate the mechanisms behind an intervention with SeQ10. The study is small and should be regarded as hypothesis-generating; however, the results are interesting and, therefore, further research in the area is needed. This study was registered at Clinicaltrials.gov, with the identifier NCT01443780.


Corporal diagnostic work and diagnostic spaces: clinicians' use of space and bodies during diagnosis.
An emerging body of literature in sociology has demonstrated that diagnosis is a useful focal point for understanding the social dimensions of health and illness. This article contributes to this work by drawing attention to the relationship between diagnostic spaces and the way in which clinicians use their own bodies during the diagnostic process. As a case study, we draw upon fieldwork conducted with a multidisciplinary clinical team providing deep brain stimulation (DBS) to treat children with a movement disorder called dystonia. Interviews were conducted with team members and diagnostic examinations were observed. We illustrate that clinicians use communicative body work and verbal communication to transform a material terrain into diagnostic space, and we illustrate how this diagnostic space configures forms of embodied 'sensing-and-acting' within. We argue that a 'diagnosis' can be conceptualised as emerging from an interaction in which space, the clinician-body, and the patient-body (or body-part) mutually configure one another. By conceptualising diagnosis in this way, this article draws attention to the corporal bases of diagnostic power and counters Cartesian-like accounts of clinical work in which the patient-body is objectified by a disembodied medical discourse.


Angiotensin-converting enzyme gene polymorphism in Behçet's disease.
Endothelial cell activation and/or injury is a characteristic feature of Behçet's disease (BD). The local renin-angiotensin system (RAS) in the vessel wall plays a prominent role in the endothelial control of vascular tonus and contributes to inflammatory processes. Angiotensin-converting enzyme (ACE) is the regulatory component of the RAS. In this study, we investigated the distribution of different alleles of the ACE gene in patients with BD, and the influence of the I/D polymorphism on different clinical manifestations of the disease. A cohort of 90 patients with BD were evaluated for their ACE genotype (male/female: 49/41, mean age: 36.9+/-10.6 years, min/max: 16-66 years). The mean duration of symptoms was 9.5+/-6.9 years (min/max: 1-35 years). The control population was composed of 30 healthy subjects (male/female: 15/15, mean age: 31.2+/-7.1 years, min/max: 20-45). The distribution of DD, ID and II genotypes of the ACE gene was 22 (24.5%), 56 (62.2%) and 12 (13.3%) for patients with BD, and 9 (30%), 16 (53.3%) and 5 (16.7%) for healthy controls, respectively. There was no significant difference between the groups (p>0.05). Similarly, there was no significant association between the ACE gene polymorphism and ocular, neurologic or vascular involvement of BD. The ACE gene polymorphism does not seem to play a role in the pathogenesis of BD. Moreover, possession of either the D or the I allele does not have an impact on the development of ocular, neurologic or vascular manifestations of the disease.


Pain relief assessment by aromatic essential oil massage on outpatients with primary dysmenorrhea: a randomized, double-blind clinical trial.
This study assessed the effectiveness of blended essential oils on menstrual cramps for outpatients with primary dysmenorrhea and explored the analgesic ingredients in the essential oils. A randomized, double-blind clinical trial was conducted. Forty-eight outpatients were diagnosed with primary dysmenorrhea by a gynecologist and had 10-point numeric rating scales that were more than 5. The patients were randomly assigned to an essential oil group (n = 24) and a synthetic fragrance group (n = 24). Essential oils blended with lavender (Lavandula officinalis), clary sage (Salvia sclarea) and marjoram (Origanum majorana) in a 2:1:1 ratio was diluted in unscented cream at 3% concentration for the essential oil group. All outpatients used the cream daily to massage their lower abdomen from the end of the last menstruation continuing to the beginning of the next menstruation. Both the numeric rating scale and the verbal rating scale significantly decreased (P < 0.001) after one menstrual cycle intervention in the two groups. The duration of pain was significantly reduced from 2.4 to 1.8 days after aromatherapy intervention in the essential oil group. Aromatic oil massage provided relief for outpatients with primary dysmenorrhea and reduced the duration of menstrual pain in the essential oil group. The blended essential oils contain four key analgesic components that amount to as much as 79.29%; these analgesic constitutes are linalyl acetate, linalool, eucalyptol, and β-caryophyllene. This study suggests that this blended formula can serve as a reference for alternative and complementary medicine on primary dysmenorrhea.


An investigation into the similarities and differences governing the cryopreservation success of koala (Phascolarctos cinereus: goldfuss) and common wombat (Vombatus ursinus: shaw) spermatozoa.
The aim of this study was to determine the relative cryopreservation success of koala and wombat spermatozoa and to investigate reasons for their respective post-thaw survival by examining the sperm's response to a range of osmotic media and determining the presence and distribution of F-actin. An hypothesis was proposed that F-actin may be imparting a degree of structural inflexibility to the koala sperm plasma membrane; hence, exposure of spermatozoa to cytochalasin D (5 microM), a F-actin depolymerisation agent, should result in increased plasticisation of the membrane and greater tolerance of cell volume changes that typically occur during cryopreservation. In experiment 1, koala (n = 4) and wombat (n = 4) spermatozoa packaged in 0.25 mL straws were cryopreserved using two freezing rates (fast-3 cm above liquid N2 interface; slow-6 degrees C/min in a freezing chamber) and two glycerol concentrations (8 and 14% v/v) in a tris-citrate glucose buffer with 15% (v/v) egg yolk. Wombat spermatozoa showed better (P < 0.01) post-thaw survival (% motile, % intact plasma membranes, % decondensed sperm heads) than koala spermatozoa. When exposed to media of varying osmolality, koala spermatozoa were less tolerant (% intact plasma membrane) of hyper-osmotic conditions (920 and 1410 mOsmol/kg) than wombat spermatozoa. F-actin was localised using a monoclonal antibody but only found in the wombat sperm head. When koala and wombat spermatozoa were exposed to media of varying osmolality, cytochalasin D had no beneficial effect on sperm survival (% intact plasma membranes). This study has demonstrated that wombat spermatozoa are highly tolerant of cryopreservation when compared to koala sperm but that spermatozoa from both species show greatest post-thaw survival when frozen slowly in 14% glycerol. Koala sperm are also particularly susceptible to hyper-osmotic environments but lack of detectable F-actin in the koala spermatozoan suggests that poor cryopreservation success in this species is unlikely to be associated with F-actin induced plasma membrane inflexibility.


Proteomic analysis reveals energy metabolic dysfunction and neurogenesis in the prefrontal cortex of a lipopolysaccharide-induced mouse model of depression.
Substantial evidence from previous studies has suggested an association between major depressive disorder (MDD) and inflammation, and previous studies have associated prefrontal cortex (PFC) dysfunction with MDD. Systemic administration of bacterial lipopolysaccharide has been used to study inflammation-associated behavioral changes in rodents. However, proteomic studies investigating PFC protein expression in an LPS-induced mouse model of depression have yet to be conducted. Using two-dimensional electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry, PFC proteomes were comparatively assessed in LPS-induced acute inflammation reaction mice, LPS-induced depressive-like behavior mice (Dep), and control mice. A total of 26 differentially expressed proteins were identified, two of which were selected for western blot analysis, the results of which revealed a significant increase in the expression levels of creatine kinase B and dihydropyrimidinase-like 3 in Dep mice, suggesting that changes in energy metabolism and neuro-genesis occur in the PFC of Dep mice. Further investigation on these processes and on the proteins of the PFC are required in order to elucidate the pathophysiological mechanism underlying MDD.


Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease.
Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians.


Kaolin as a management alternative for insecticide-resistant navel orangeworm (Lepidoptera: Pyralidae).
The production of almonds and pistachios in California's Central Valley employs insecticides for the management of their primary pest, navel orangeworm. The pyrethroid Bifenthrin is commonly used, and now a strain of Amyelois transitella Walker (Lepidoptera: Pyralidae) (R347) obtained from Kern County almond orchards with a history of Bifenthrin use has acquired >110-fold resistance toward pyrethroids. One method to improve control is to use additives and spray adjuvants, which are applied simultaneously with an insecticide to increase coverage and/or duration of control. We tested 2 levels of the naturally occurring clay Kaolin as an additive, alone and in combination with either Bifenthrin or the diamide Chlorantraniliprole, to determine if it could reduce feeding damage and decrease survival of pyrethroid-resistant A. transitella on almonds in the laboratory and improve the efficacy of Chlorantraniliprole in the field. Larval performance was measured for the strains R347 and ALM (34.7-fold resistance compared to susceptible lab strain) reared on treated almonds. Strain R347 had 1.9-fold greater survival and caused 1.3-fold more feeding damage than strain ALM across all treatments, although both strains were susceptible to the combination of Kaolin + insecticide. Kaolin synergized Bifenthrin for R347, decreasing survival by 10.0%. Kaolin did not reduce feeding damage for either strain. When combined with insecticide, feeding damage was similar to insecticide alone, but the addition of Kaolin to the insecticide generally decreased survival more than the insecticide alone. In the field, the addition of Kaolin to Chlorantraniprole during application helped retain activity against this challenging pest.


Semi-Quantitative Targeted Gas Chromatography-Mass Spectrometry Profiling Supports a Late Side-Chain Reductase Cycloartenol-to-Cholesterol Biosynthesis Pathway in Brown Algae.
Sterols are biologically important molecules that serve as membrane fluidity regulators and precursors of signaling molecules, either endogenous or involved in biotic interactions. There is currently no model of their biosynthesis pathways in brown algae. Here, we benefit from the availability of genome data and gas chromatography-mass spectrometry (GC-MS) sterol profiling using a database of internal standards to build such a model. We expand the set of identified sterols in 11 species of red, brown, and green macroalgae and integrate these new data with genomic data. Our analyses suggest that some metabolic reactions may be conserved despite the loss of canonical eukaryotic enzymes, like the sterol side-chain reductase (SSR). Our findings are consistent with the principle of metabolic pathway drift through enzymatic replacement and show that cholesterol synthesis from cycloartenol may be a widespread but variable pathway among chlorophyllian eukaryotes. Among the factors contributing to this variability, one could be the recruitment of cholesterol biosynthetic intermediates to make signaling molecules, such as the mozukulins. These compounds were found in some brown algae belonging to Ectocarpales, and we here provide a first mozukulin biosynthetic model. Our results demonstrate that integrative approaches can already be used to infer experimentally testable models, which will be useful to further investigate the biological roles of those newly identified algal pathways.


Issues in solid-organ transplantation in children: translational research from bench to bedside.
In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.


(E)-N,N-Diethyl-2,6-diisopropyl-4-[2-(4-nitro-phen-yl)ethen-yl]aniline.
The title compound, C24H32N2O2, was prepared by Horner olefination of 4-di-ethyl-amino-3,5-diiso-propyl-benzaldehyde and diethyl p-nitro-benzyl-phospho-nate. There are two independent mol-ecules (A and B) in the asymmetric unit. Their main axes, defined by the line connecting the N atoms of the nitro and amino groups, open an angle of 79.42 (3)°. Steric hindrance around the amino group is reflected in a long aryl C-N bond [1.434 (3) Å for mol-ecule A and 1.440 (3) Å for mol-ecule B], a pyramidal geometry [angle sum = 350.0 (2)° for mol-ecule A and 349.6 (2)° for mol-ecule B], and dihedral angles between the phenyl-ene group and the plane defined by the CH2-N-CH2 unit of 86.9 (3)° for mol-ecule A and 88.3 (3)° for mol-ecule B. This gives structural support for the electronic decoupling of the amino group from the nearly planar nitro-stilbene moiety (r.m.s. deviation for C, N and O atoms = 0.097 for mol-ecule A and 0.107 Å for mol-ecule B).


Inflammatory response in mouse lungs to haze episodes under different backgrounds of particulate matter exposure.
Particulate matter (PM) toxicity has mostly been investigated through in vitro exposure or tracheal infusion in animal models. However, given the complexity of ambient conditions, most animal studies do not mimic real-life PM exposure. In this work, we established a novel integrated exposure model to study the dynamic inflammatory response and defense strategies in ambient PM-exposed mice. Three groups of male C57BL/6 mice were kept in three chambers with pre-exposure to filtered air (FA), unfiltered air (UFA), or the air with a low PM concentration (PM2.5 ≤ 75 μg/m3) (LPM), respectively, for 37 days. Then all three groups of mice were exposed to haze challenge for 3 days, followed by exposure in filtered air for 7 days to allow recovery. Our results suggest that following a haze challenge, the defense strategies of mice of filtered air (FA) and low PM (LPM) groups comprised a form of "counterattack", whereas the response of the unfiltered air (UFA) group could be viewed as a "silence". While the latter strategy protected the lung tissues of mice from acute inflammatory damage, it also foreshadowed the development of chronic inflammatory diseases. These findings contribute to explaining previously documented PM-associated pathogenic mechanisms.


Mind the Gaps: A Qualitative Study Combining Patients' and Nurses' Reflections on Pain Care.
Chronic noncancer pain is a serious health problem, one that is often associated with physical debility and emotional suffering. Although chronic noncancer pain is one of the primary reasons that people seek medical care, a significant body of evidence indicates that chronic pain is underdiagnosed and undertreated. There is a consensus among professional stakeholders in pain care that there is a need to strengthen quality, capacity, and competence in pain management at all levels of health care. Thus, there is a need for more in-depth knowledge of both the recipients and the providers of pain care, and qualitative studies can contribute to this. The aim is to explore and combine the perspectives of patients receiving pain care and registered nurses providing care at pain clinics. A multimethod design was based on two qualitative studies consisting of semistructured interviews with patients receiving pain care (N = 10) and nurses providing pain care at pain clinics (N = 10). Qualitative content analysis was applied to interpret and abstract their experiences. The themes developed from triangulation revealed significant gaps between ideal pain care and actual practice: "Dissonance in reflections on personalized care," "A corresponding need for improved information flow in all levels," and "A corresponding need for improved structure in pain care." We suggest a stronger commitment to efficient information flow and person-centered communication to facilitate the patient involvement and self-management. In addition, more resources, education, and training are necessary to enable nurses and other professionals to act upon guidelines and ensure effective pain care.


Determining energy expenditure in a large seabird using accelerometry.
The trade off between energy gained and expended is the foundation of understanding how, why and when animals perform any activity. Based on the concept that animal movements have an energetic cost, accelerometry is increasingly being used to estimate energy expenditure. However, validation of accelerometry as an accurate proxy for field metabolic rate in free-ranging species is limited. In the present study, Australasian gannets (Morus serrator) from the Pope's Eye colony (38°16'42″S 144°41'48″E), south-eastern Australia, were equipped with GPS and tri-axial accelerometers and dosed with doubly labelled water (DLW) to measure energy expenditure during normal behaviour for 3-5 days. The correlation between daily energy expenditure from the DLW and vectorial dynamic body acceleration (VeDBA) was high for both a simple correlation and activity-specific approaches (R2=0.75 and 0.80, respectively). Varying degrees of success were observed for estimating at-sea metabolic rate from accelerometry when removing time on land using published energy expenditure constants (R2=0.02) or activity-specific approaches (R2=0.42). The predictive capacity of energy expenditure models for total and at-sea periods was improved by the addition of total distance travelled and proportion of the sampling period spent at sea during the night, respectively (R2=0.61-0.82). These results indicate that accelerometry can be used to estimate daily energy expenditure in free-ranging gannets and its accuracy may depend on the inclusion of movement parameters not detected by accelerometry.


White-Tailed Eagle (Haliaeetus albicilla) Body Feathers Document Spatiotemporal Trends of Perfluoroalkyl Substances in the Northern Environment.
We reconstructed the first long-term (1968-2015) spatiotemporal trends of perfluoroalkyl substances (PFAS) using archived body feathers of white-tailed eagles (Haliaeetus albicilla) from the West Greenland (n = 31), Norwegian (n = 66), and Central Swedish Baltic coasts (n = 50). We observed significant temporal trends of perfluorooctane sulfonamide (FOSA), perfluorooctane sulfonate (PFOS), and perfluoroalkyl carboxylates (∑PFCAs) in all three subpopulations. Concentrations of FOSA and PFOS had started decreasing significantly since the mid-1990s to 2000 in the Greenland and Norwegian subpopulations, consistent with the 3M phase-out, though in sharp contrast to overall increasing trends observed in the Swedish subpopulation. Moreover, ∑PFCA concentrations significantly increased in all three subpopulations throughout the study periods. These temporal trends suggest on-going input of PFOS in the Baltic and of ∑PFCAs in all three regions. Considerable spatial variation in PFAS concentrations and profiles was observed: PFOS concentrations were significantly higher in Sweden, whereas FOSA and ∑PFCA concentrations were similar among the subpopulations. PFOS dominated the PFAS profiles in the Swedish and Norwegian subpopulations, in contrast to the domination of FOSA and ∑PFCAs in the Greenland one. Our spatiotemporal observations underline the usefulness of archived bird of prey feathers in monitoring spatiotemporal PFAS trends and urge for continued monitoring efforts in each of the studied subpopulations.


Operculina turpethum (Linn.) Silva Manso as a Medicinal Plant Species: A Review on Bioactive Components and Pharmacological Properties.
Operculina turpethum (Linn.) (OT) Silva Manso belongs to the family Convolvulaceae. This review incorporates literature for the phytochemical and pharmacological profile of OT herb. Exhaustive literature survey was done using all the details on phytochemistry and pharmacology of OT available. This herb was found to be a potent source of bioactive compounds such as α- and β-turpethein, turpethinic acids (A, B, C, D, and E), coumarins, cycloartenol, lanosta-5-ene, 24-methylene-δ-5-lanosterol, α- and β-rhamnose, β-sitosterol, lupeol, scopoletin, betulin, acrylamide, stigma-5,22dien-3-O-β-D-glucopyranoside, β-sitosterol-β-D-glucoside (H-1), 22,23-dihydro-α-spinosterol-β-D-glucoside (H-2), and salicylic acid (CH-2), which are useful in fevers, edema, ascites, anorexia, constipation, hepatosplenomegaly, hemorrhoids, cervical lymphadenitis, fistulas, constipation, chronic gout, fever, bronchitis, ulcers, hemorrhoids, tumors, obesity, jaundice, herpes, induce lacrimation, and other skin disorders. From the aerial parts of OT, four new dammarane-type saponins that are operculinosides A-D (1-4) were isolated that showed particular hepatoprotective activities. All the compounds are reported to possess pharmacological properties such as antibacterial, anti-inflammatory, analgesic, hepatoprotective, anti-arthritic, ulcer protective, antidiarrheal, antidiabetic, and cytotoxic properties.


Striatal postsynaptic ultrastructural alterations following methylenedioxymethamphetamine administration.
Amphetamine derivatives, such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), act as monoaminergic neurotoxins in the central nervous system. Although there are slight differences in their mechanism of action, these compounds share a final common pathway, which involves dopamine release and oxidative stress. Apart from striatal toxicity involving monoamine axons, no previous report evidenced any alteration at the striatal level concerning postsynaptic sites. Given the potential toxicity for extracellular dopamine at the striatal level, and the hypothesis for neurotoxic effects of dopamine on striatal medium-sized neurons in Huntington's disease, we evaluated at an ultrastructural level the effects of MDMA on intrinsic striatal neurons of the mouse. In this study, administering MDMA, we noted ultrastructural alterations of striatal postsynaptic GABAergic cells consisting of neuronal inclusions shaped as whorls of concentric membranes. These whorls stained for ubiquitin but not for synuclein and represent the first morphologic correlate of striatal postsynaptic effects induced by MDMA.


Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.
Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.


Antimicrobial stewardship in residential aged care facilities: need and readiness assessment.
Information about the feasibility, barriers and facilitators of antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has been scant. Exploring the prevailing perceptions and attitudes of key healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS in the RACF setting is imperative to guide AMS interventions. Semi-structured interviews and focus groups were conducted with key RACF healthcare providers until saturation of themes occurred. Participants were recruited using purposive and snowball sampling. The framework approach was applied for data analysis. A total of 40 nurses, 15 general practitioners (GPs) and 6 pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions of current antibiotic prescribing behaviour, perceptions of antibiotic resistance, attitude towards and understanding of AMS, perceived barriers to and facilitators of AMS implementation, and feasible AMS interventions. A higher proportion of GPs and pharmacists compared with nurses felt there was over-prescribing of antibiotics in the RACF setting. Antibiotic resistance was generally perceived as an issue for infection control rather than impacting clinical decisions. All key stakeholders were supportive of AMS implementation in RACFs; however, they recognized barriers related to workload and logistical issues. A range of practical AMS interventions were identified, with nursing-based education, aged-care specific antibiotic guidelines and regular antibiotic surveillance deemed most useful and feasible. Areas of antibiotic over-prescribing have been identified from different healthcare providers' perspectives. However, concern about the clinical impact of antibiotic resistance was generally lacking. Importantly, information gathered about feasibility, barriers and facilitators of various AMS interventions will provide important insights to guide development of AMS programs in the RACF setting.


Preclinical PET imaging of glycoprotein non-metastatic melanoma B in triple negative breast cancer: feasibility of an antibody-based companion diagnostic agent.
High levels of expression of glycoprotein non-metastatic B (gpNMB) in triple negative breast cancer (TNBC) and its association with metastasis and recurrence make it an attractive target for therapy with the antibody drug conjugate, glembatumumab vedotin (CDX-011). This report describes the development of a companion PET-based diagnostic imaging agent using 89Zr-labeled glembatumumab ([89Zr]DFO-CR011) to potentially aid in the selection of patients most likely to respond to targeted treatment with CDX-011. [89Zr]DFO-CR011 was characterized for its pharmacologic properties in TNBC cell lines. Preclinical studies determined that [89Zr]DFO-CR011 binds specifically to gpNMB with high affinity (Kd = 25 ± 5 nM), immunoreactivity of 2.2-fold less than the native CR011, and its cellular uptake correlates with gpNMB expression (r = 0.95). In PET studies at the optimal imaging timepoint of 7 days p.i., the [89Zr]DFO-CR011 tumor uptake in gpNMB-expressing MDA-MB-468 xenografts had a mean SUV of 2.9, while significantly lower in gpNMB-negative MDA-MB-231 tumors with a mean SUV of 1.9. [89Zr]DFO-CR011 was also evaluated in patient-derived xenograft models of TNBC, where tumor uptake in vivo had a positive correlation with total gpNMB protein expression via ELISA (r = 0.79), despite the heterogeneity of gpNMB expression within the same group of PDX mice. Lastly, the radiation dosimetry calculated from biodistribution studies in MDA-MB-468 xenografts determined the effective dose for human use would be 0.54 mSv/MBq. Overall, these studies demonstrate that [89Zr]DFO-CR011 is a potential companion diagnostic imaging agent for CDX-011 which targets gpNMB, an emerging biomarker for TNBC.


Isometric dynamic response of mammalian heart muscle due to step changes in the calcium concentration of the perfusing medium.
The isometric tension transient response of isolated kitten papillary muscle was found to exhibit direction-dependent dynamics when subjected to step changes in the calcium concentration of the bathing medium. The tension transient curves could be resolved into a minimum of two to three exponential components, which could be considered to indicate different calcium compounds or compartments within the muscle. However, a model relating calcium diffusion across the muscle to the dose-response curve indicates that the exponential components of the tension transient curves are due to the properties of calcium diffusion through the extracellular space, and that the direction-dependent dynamics are caused by the nonlinearity of the dose-response curve.


Outcome of conservative and minimally invasive management in emphysematous pyelonephritis.
Developing countries. Emphysematous pyelonephritis (EPN) is a urologic emergency characterized by acute necrotizing infection with the presence of gas in the kidney, perinephric space, and/or urinary collecting system. It is a retrospective study of inpatients at the Department of Urology, RG Kar Medical College and Hospital, Kolkata, which includes twenty patients diagnosed as EPN between September of 2018 and May of 2020. Patients were classified as per computed tomography (CT) severity grading proposed by Huang and Tseng. In our study, medical management with antibiotics was effective in 10% of patients. Twenty percent of patients were treated with medical management and internal ureteral stenting. Fifty percent of the patients were treated with medical management and percutaneous nephrostomy (PCN). Ten percent needed PCN drainage in addition to Double J (DJ) stenting. Ten percent needed percutaneous drainage of perinephric abscess along with PCN. Ten percent of patients were treated with open drainage in addition to DJ stenting and percutaneous drainage of perinephric collection as they failed to respond to minimally invasive intervention alone, with repeat ultrasonography showing persistent collection. There was no mortality in the group. EPN patients are mostly moribund with multiple comorbidities. It is vital to comprehend the management with a prompt CT imaging. Proactive hemodynamic stabilization, antimicrobial therapy, complementing it with DJ stenting and/or PCN in cases not responding to antibiotics alone, can treat most of the patients with this pathology.


Consumption of rice, acceptability and sensory qualities of fortified rice amongst consumers of social safety net rice in Nepal.
Micronutrient deficiencies are prevalent in Nepal where starchy foods constitute a large proportion of diets and consumption of micronutrient-rich foods is inadequate. We conducted a study to determine whether rice would be an appropriate vehicle for micronutrient fortification in Nepal. In Bajura in remote rural Nepal, we conducted a household survey to characterize rice intakes in 195 households, and a double-blinded acceptability test with 177 social safety net rice consumers ≥18 years of age. Of these, 168 tasted fortified and unfortified rice to assess whether respondents could differentiate between fortified and non-fortified rice and their sensory properties. Rice was fortified by blending hot extruded kernels containing 6 micronutrients together with non-fortified rice at a 1:99 ratio. We used binomial tests to assess whether participants could correctly differentiate fortified rice, from non-fortified rice and paired t-tests to compare scores for sensory qualities of cooked fortified and non-fortified rice. We used multiple regression to test associations between per capita consumption and age, gender, wealth and food security. Per capita consumption of rice (median 216g/day, IQR 144.0, 288.0) did not vary by wealth but was +52.08g, (95% CI 10.43, 93.72) higher amongst moderately to severely food insecure households compared with food secure / mildly food insecure. Most respondents could not differentiate fortified rice from non-fortified rice: 37.5% identified uncooked fortified rice and 39.3% cooked rice, which was not different from the 33% expected by chance (p = 0.22 and p = 0.09 respectively). The sensory qualities of fortified rice were acceptable (scoring 3.9 out of 5) and did not differ from non-fortified rice (p>0.05). A rice fortification programme implemented through the Nepal Food Corporation's social safety nets has potential because purchase and consumption of rice is high and fortified rice is acceptable among consumers in remote food insecure areas of Nepal.


Multiparametric magnetic resonance imaging - Transrectal ultrasound-guided cognitive fusion biopsy of the prostate: Clinically significant cancer detection rates stratified by the Prostate Imaging and Data Reporting System version 2 assessment category.
We aimed to report the clinically significant prostate cancer (PCa) detection rate in men undergoing magnetic resonance imaging-transrectal ultrasound (MRI-TRUS)-cognitive fusion (CF) targeted biopsies stratified by the Prostate Imaging and Data Reporting System (PI-RADS) version 2 (v2) scores. With a quality assurance waiver from the IRB, we identified a cohort of men who underwent MRI-TRUS-CF and synchronous template biopsy from 2015-2017. MRI (PI-RADS v2 score, lesion size, lesion location [peripheral or transition zone (PZ/TZ)]), and CF-TRUS biopsy (operator experience, TRUS visibility, and number of biopsies) features were extracted. The primary outcome was diagnosis of clinically significant (Gleason score ≥3+4=7 or International Society of Urological Pathology (ISUP) grade group ≥2) PCa. During the study period, 131 men (with 142 PIRADS v2 score ≥3 lesions) met inclusion criteria; 98 men had previously negative template biopsy and 33 were on active surveillance for previously detected low-grade PCa. In total, 41.9% (55/131) men had clinically significant PCa - 17.6% (23/131) detected on targeted biopsy only, 8.4% (11/131) on template biopsy only, and 16.0% (21/131) on both targeted and template biopsy. Clinically significant PCa detection stratified by PI-RADS v2 scores were: 11.1% (3/27) for score 3 (indeterminate), 42.9% (24/56) for score 4 (significant cancer likely), and 35.6% (21/59) for score 5 (significant cancer very likely). Clinically significant PCa detection rates in targeted biopsies were better among PZ (41.8% [33/79]) compared to TZ (23.8% [15/63]) lesions (p=0.025) in TRUS visible lesions (p=0.033) and in the most experienced radiologists (p=0.05), with no difference by lesion size or number of additional core biopsies performed (all p>0.05). Cognitive fusion MRI-TRUS-guided targeted biopsy yielded substantially lower rates of clinically significant cancer in PI-RADS v2 score 4 and 5 lesions when compared to published results using in-bore MR-guided or automated MRI-TRUS fusion guidance systems. Cancer detection was worst for TZ lesions.


Proteomics of extracellular vesicles: Exosomes and ectosomes.
Almost all bacteria, archaea, and eukaryotic cells shed extracellular vesicles either constitutively or in a regulated manner. These nanosized membrane vesicles are spherical, bilayered proteolipids that harbor specific subsets of proteins, DNAs, RNAs, and lipids. Recent research has facilitated conceptual advancements in this emerging field that indicate that extracellular vesicles act as intercellular communicasomes by transferring signals to their target cell via surface ligands and delivering receptors and functional molecules. Recent progress in mass spectrometry-based proteomic analyses of mammalian extracellular vesicles derived from diverse cell types and body fluids has resulted in the identification of several thousand vesicular proteins that provide us with essential clues to the molecular mechanisms involved in vesicle cargo sorting and biogenesis. Furthermore, cell-type- or disease-specific vesicular proteins help us to understand the pathophysiological functions of extracellular vesicles and contribute to the discovery of diagnostic and therapeutic target proteins. This review focuses on the high-throughput mass spectrometry-based proteomic analyses of mammalian extracellular vesicles (i.e., exosomes and ectosomes), EVpedia (a free web-based integrated database of high-throughput data for systematic analyses of extracellular vesicles; http://evpedia.info), and the intravesicular protein-protein interaction network analyses of mammalian extracellular vesicles. The goal of this article is to encourage further studies to construct a comprehensive proteome database for extracellular vesicles that will help us to not only decode the biogenesis and cargo-sorting mechanisms during vesicle formation but also elucidate the pathophysiological roles of these complex extracellular organelles.


Toward late career transitioning: a proposal for academic surgeons.
In the absence of a defined retirement age, academic surgeons need to develop plans for transition as they approach the end of their academic surgical careers. The development of a plan for late career transition represents an opportunity for departments of surgery across Canada to initiate a constructive process in cooperation with the key stakeholders in the hospital or institution. The goal of the process is to develop an individual plan for each faculty member that is agreeable to the academic surgeon; informs the surgical leadership; and allows the late career surgeon, the hospital, the division and the department to make plans for the future. In this commentary, the literature on the science of aging is reviewed as it pertains to surgeons, and guidelines for late career transition planning are shared. It is hoped that these guidelines will be of some value to academic programs and surgeons across the country as late career transition models are developed and adopted.


The candidate sex-reversing DAX1 gene is autosomal in marsupials: implications for the evolution of sex determination in mammals.
The human X-linked DAX1 gene was cloned from the region of the short arm of the human X found in duplicate in sex-reversed Xdup Y females (E. Zanaria et al., 1994, Nature 372: 635-641). DAX1 is suggested to be required for ovarian differentiation and to play an important role in mammalian sex determination or differentiation pathways. Its proposed dose-dependent effect on sexual development suggests that DAX1 could represent an evolutionary link with an ancestral sex-determining mechanism that depended on the dosage of an X-linked gene. Furthermore, DAX1 could also represent the putative X-linked switch gene, which independently controls sexual dimorphisms in marsupial mammals in an X-dose-dependent manner (D.W. Cooper et al., 1993, Semin. Dev. 4: 117-128). If DAX1 has a present role in marsupial sexual differentiation or had an ancestral role in mammalian sex determination, it would be expected to lie on the marsupial X chromosome, despite the autosomal localization of other human Xp genes. We therefore cloned and mapped the DAX1 gene in the tammar wallaby (Macropus eugenii). DAX1 was located on wallaby chromosome 5p near other human Xp genes, indicating that it was originally autosomal and that it is not involved in X-linked dose-dependent sex determination in an ancestral mammal nor in marsupial sexual differentiation.


Balance and Falls in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Prospective Study.
Individuals with chronic obstructive pulmonary disease (COPD) have demonstrated balance impairment and a higher fall incidence. However, these have not been investigated in acute exacerbations of the disease (ECOPD). This study evaluates balance in patients during an ECOPD compared to stable COPD and healthy controls, and examines the fall incidence rate after hospitalisation due to ECOPD compared to individuals with stable COPD. Balance performance of 26 hospitalised patients with ECOPD was compared to 26 community-dwelling participants with stable COPD and 25 matched healthy controls. Balance was evaluated using computerised posturography and the Berg Balance Scale (BBS). Prospective falls were monitored by monthly calendars for 12 months in both COPD groups. Compared to controls, greater balance impairment was observed during ECOPD for most posturography variables across standing conditions (p ≤ 0.05). Both COPD groups had worse BBS scores (p ≤ 0.05) compared to controls. Increased dyspnoea and reduced quadriceps' strength were associated with impaired balance performance. A higher fall incidence (1.76 falls/person/year) was observed following hospitalisation in patients with ECOPD compared to stable COPD (0.53 falls/person/year) at 12 months. Patients with ECOPD demonstrate balance impairments which are associated with increased dyspnoea and reduced muscle strength. Balance impairment during ECOPD may contribute to a high incidence of falls following hospitalisation.


[Clinical effect of distally-based dorsal thumb neurocutaneous vascular flap on repair of soft tissue defect in thumb].
To investigate the surgical methods and clinical results of repairing soft tissue defects in the thumb with distally-based dorsal thumb neurocutaneous vascular flap. From January 2006 to October 2007, 23 patients with soft tissue defect in the thumb were treated, including 20 males and 3 females aged 19-46 years old (average 27.5 years old). The defect was caused by crush injury in 1 case, electric planer accident in 6 cases, incised injury in 8 cases, and avulsion injury in 8 cases. The defect was located on the palmar aspect of the thumb distal phalanx in 3 cases, the dorsal-radial aspect of the thumb distal phalanx in 3 cases, and ulnar or dorsal aspect in 17 cases. The defect size ranged from 3.3 cm x 1.2 cm to 4.2 cm x 1.2 cm. Among them, 18 cases were complicated with distal 1/2 nail bed defect or injury. The time between injury and hospital admission was 1-72 hours (average 22 hours). During operation, the defect was repaired with distally-based dorsal-radial neurovenocutaneous vascular flap of the thumb in 3 cases and distally-based dorsal-ulnar neurovenocutaneous vascular flap of the thumb in 20 cases. The size of those flaps was 4.0 cm x 1.6 cm-5.0 cm x 3.0 cm. The donor site underwent direct suture or split thickness skin graft repair. At 10 days after operation, 3 cases suffered from the epidermal necrosis in the distal part of the flap, 2 of them experienced the exfoliation of dark scab 14 days later and the flap survived, and the flap of the rest one survived after dressing change. The other flaps and the skin graft at the donor site all survived uneventfully. The wounds healed by first intention. All the patients were followed up for 10-16 months (average 12.6 months). The flaps were soft in texture and full in appearance. The two-point discrimination value 6 months after operation was 8-10 mm. At 12 months after operation, the growth of the residual fingernail was evident in 18 cases, including 4 cases of curved or hook fingernail. Active flexion and extension of the thumb were normal. The abduction of the first web space reached or surpassed 80 percent of the normal side in 20 cases and was below 80 percent of the normal side in 3 cases. The clinical outcomes were satisfactory in 11 cases, approximately satisfactory in 8 cases, and unsatisfactory in 4 cases according to self-designed evaluation system. The operative method of repairing the soft tissue defects in the thumb with the distally-based dorsal thumb neurocutaneous vascular flap is simple, stable in anatomy, in line with the principle of proximity, and suitable for repairing thumb tip defect 3 cm in size. It can bring a good postoperative appearance of the thumb and little influence on the hand function.


Difficult tracheal intubation--analysis and management in 37 cases.
To analyse the anatomical features of difficult airways encountered during general anaesthesia and study how difficult intubation was circumvented during anaesthesia in our local population. Difficult intubation was defined as failure to visualise the larynx during laryngoscopy after neck flexion and external cricoid pressure was applied. All cases of difficult intubation collected over 1 1/2 years during general anaesthesia were recorded prospectively and analysed. Thirty-seven cases of difficult intubation were identified among 5,379 cases of general anaesthesia requiring endotracheal intubation. 40.5% of the cases were not expected to be difficult pre-operatively. 5.4% of the cases were Lehane II, 91.9% Lehane III and 2.7% Lehane IV. The anatomical features encountered included receding chin, limited mouth opening, limited neck extension, abnormal dentition, short thyromental distance, large tongue, supraglottic mass and floppy epiglottis. Gum elastic bougie was commonly used to overcome the intubation difficulties. Laryngeal mask, blind nasal tracheal intubation, fiberoptic bronchoscopic intubation and sometimes an alternative anaesthetic technique, such as regional anaesthesia, were resorted to. Assessment of multiple anatomical features would improve prediction of difficult intubation. Assessment of receding chin, neck extension, mouth opening, teeth, tongue size, thyromental distance might pick up 81% of difficult airways. Unexpected problems with epiglottis and glottic inlet are the potential sources of danger that are difficult to predict pre-operatively.


Place of death and associated factors in 12 Latin American countries: A total population study using death certificate data.
Little is known about place of death in Latin America, although this data are crucial for health system planning. This study aims to describe place of death and associated factors in Latin America and to identify factors that contribute to inter-country differences in place of death. We conducted a total population observational study using death certificates of the total annual decedent populations in 12 countries (Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Ecuador, Mexico, Paraguay, Peru, and Uruguay) for the most recent available year (2016, 2017, or 2018). Data were analysed regarding place of death and multivariable logistic regression with place of death as the dependent variable was used to examine associated clinical and sociodemographic factors (independent variables) in each of the countries. The total study sample was 2 994 685 deaths; 31.3% of deaths occurred at home, and 57.6% in hospitals. A strong variation was found among the countries with home deaths ranging from 20% (Brazil) to 67.9% (Guatemala) and hospital deaths from 22.3% (Guatemala) to 69.5% (Argentina). These differences between countries remained largely unchanged after controlling for sociodemographic factors and causes of death. The likelihood of dying at home was consistently higher with increasing age, for those living in a rural area, and for those with a lower educational level (except in Argentina). Most deaths in Latin America occur in hospitals, with a strong variation between countries. As clinical and sociodemographic factors included in this study did not explain country differences, other factors such as policy and health care system seem to have a crucial impact on where people die in Latin America.


2B4 is constitutively associated with linker for the activation of T cells in glycolipid-enriched microdomains: properties required for 2B4 lytic function.
2B4 is a receptor belonging to the Ig superfamily and is found on all murine NK cells as well as a small subset of T cells. Previous studies have found that cross-linking of the 2B4 receptor results in both increased cytotoxicity and IFN-gamma secretion. We have discovered that 2B4 from transfected NK and T cell lines, as well as from primary murine cells, coimmunoprecipitates with the phosphoprotein linker for the activation of T cells (LAT), which is essential for TCR-mediated signaling. This association is independent of both 2B4 phosphorylation and the cytoplasmic tail of 2B4. We have found that, along with LAT, 2B4 is constitutively located in glycolipid-enriched microdomains of the plasma membrane. In fact, 2B4 appears to associate with LAT only when it localizes to glycolipid-enriched microdomains. This localization of 2B4 occurs due to a CxC cysteine motif found in the transmembrane region, as determined by mutagenesis studies. 2B4-mediated cytotoxicity is defective in the absence of LAT, indicating that LAT is a required intermediate for 2B4 signal transduction. However, we have also shown that LAT association alone is not sufficient for maximal 2B4 activation.


Mycobiome of the bat white nose syndrome affected caves and mines reveals diversity of fungi and local adaptation by the fungal pathogen Pseudogymnoascus (Geomyces) destructans.
Current investigations of bat White Nose Syndrome (WNS) and the causative fungus Pseudogymnoascus (Geomyces) destructans (Pd) are intensely focused on the reasons for the appearance of the disease in the Northeast and its rapid spread in the US and Canada. Urgent steps are still needed for the mitigation or control of Pd to save bats. We hypothesized that a focus on fungal community would advance the understanding of ecology and ecosystem processes that are crucial in the disease transmission cycle. This study was conducted in 2010-2011 in New York and Vermont using 90 samples from four mines and two caves situated within the epicenter of WNS. We used culture-dependent (CD) and culture-independent (CI) methods to catalogue all fungi ('mycobiome'). CD methods included fungal isolations followed by phenotypic and molecular identifications. CI methods included amplification of DNA extracted from environmental samples with universal fungal primers followed by cloning and sequencing. CD methods yielded 675 fungal isolates and CI method yielded 594 fungal environmental nucleic acid sequences (FENAS). The core mycobiome of WNS comprised of 136 operational taxonomic units (OTUs) recovered in culture and 248 OTUs recovered in clone libraries. The fungal community was diverse across the sites, although a subgroup of dominant cosmopolitan fungi was present. The frequent recovery of Pd (18% of samples positive by culture) even in the presence of dominant, cosmopolitan fungal genera suggests some level of local adaptation in WNS-afflicted habitats, while the extensive distribution of Pd (48% of samples positive by real-time PCR) suggests an active reservoir of the pathogen at these sites. These findings underscore the need for integrated disease control measures that target both bats and Pd in the hibernacula for the control of WNS.


Radiation therapy for local-regional recurrences of rectal carcinoma following primary surgery.
Several studies have emphasized the role of radiation therapy for patients with pelvic recurrences of rectal carcinoma following primary surgery. The occurrence of local-regional relapse usually means a poor prognosis and often a poor quality of life, so that different authors consider the prognosis of patients relapsing after surgery worse than those with primary inoperable tumors or those with residual disease after resection. Between January 1988 and January 1995, 43 patients with local recurrence of rectal carcinoma were treated at our Institution. Twenty-three had previously been operated by abdominoperineal resection and 20 by anterior resection. Thirteen cases also received adjuvant chemotherapy. All patients underwent irradiation with a 6-15 MeV linear accelerator; 8 (19%) received a total dose of up to 45 Gy on the pelvis and 35 (81%) higher than 45 Gy. Eighteen cases (42%) underwent 3-6 courses of chemotherapy with 5-fluorouracil and folates during radiation. Treatment tolerance was satisfactory. All cases underwent restaging at 45 days from completion of treatment. Sixteen cases (37%) showed a radiologic response > 50%. Median overall survival after relapse was 18.8 months. There were no statistical significant differences in survival between patients treated exclusively with radiation and those treated with chemo-radiotherapy (17 vs 22 months). The results of patients who received doses higher than 45 Gy were statically better (P < 0.05) than those irradiated up to 45 Gy. A slight increase in survival was demonstrated in cases submitted to radical surgery after combined treatment (25 months). Twenty-seven cases (63%) obtained pain control after radiation therapy (median pain remission, 11 months). Our results seem to encourage radiation therapists, surgeons and oncologists to have a more curative attitude in the treatment of selected patients with local-regional recurrences of rectal cancers by using multi-modality therapy.


Gap analysis on the biology of Mediterranean marine fishes.
We estimated the current level of knowledge concerning several biological characteristics of the Mediterranean marine fishes by carrying out a gap analysis based on information extracted from the literature, aiming to identify research trends and future needs in the field of Mediterranean fish biology that can be used in stock assessments, ecosystem modeling and fisheries management. Based on the datasets that emerged from the literature review, there is no information on any biological characteristic for 43% (n = 310) of the Mediterranean fish species, whereas for an additional 15% (n = 109) of them there is information about just one characteristic. The gap between current and desired knowledge (defined here as having information on most biological characteristics for at least half of the Mediterranean marine fishes) is smaller in length-weight relationships, which have been studied for 43% of the species, followed by spawning (39%), diet (29%), growth (25%), maturity (24%), lifespan (19%) and fecundity (17%). The gap is larger in natural mortality for which information is very scarce (8%). European hake (Merluccius merluccius), red mullet (Mullus barbatus), annular seabream (Diplodus annularis), common pandora (Pagellus erythrinus), European anchovy (Engraulis encrasicolus), European pilchard (Sardina pilchardus) and bogue (Boops boops) were the most studied species, while sharks and rays were among the least studied ones. Only 25 species were fully studied, i.e. there was available information on all their biological characteristics. The knowledge gaps per characteristic varied among the western, central and eastern Mediterranean subregions. The number of available records per species was positively related to total landings, while no relationship emerged with its maximum reported length, trophic level and commercial value. Future research priorities that should be focused on less studied species (e.g. sharks and rays) and mortality/fecundity instead of length-weight relationships, as well as the economy of scientific sampling (using the entire catch to acquire data on as many biological characteristics as possible) are discussed.