Short-chain fatty acids in control of body weight and insulin sensitivity.
The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.


Tripartite organization of the ventral stream by animacy and object size.
Occipito-temporal cortex is known to house visual object representations, but the organization of the neural activation patterns along this cortex is still being discovered. Here we found a systematic, large-scale structure in the neural responses related to the interaction between two major cognitive dimensions of object representation: animacy and real-world size. Neural responses were measured with functional magnetic resonance imaging while human observers viewed images of big and small animals and big and small objects. We found that real-world size drives differential responses only in the object domain, not the animate domain, yielding a tripartite distinction in the space of object representation. Specifically, cortical zones with distinct response preferences for big objects, all animals, and small objects, are arranged in a spoked organization around the occipital pole, along a single ventromedial, to lateral, to dorsomedial axis. The preference zones are duplicated on the ventral and lateral surface of the brain. Such a duplication indicates that a yet unknown higher-order division of labor separates object processing into two substreams of the ventral visual pathway. Broadly, we suggest that these large-scale neural divisions reflect the major joints in the representational structure of objects and thus place informative constraints on the nature of the underlying cognitive architecture.


Can Cognitive Behavioral Therapy for Insomnia also treat fatigue, pain, and mood symptoms in individuals with traumatic brain injury? - A multiple case report.
Individuals with traumatic brain injury (TBI) often develop sleep disorders post-injury. The most common one is insomnia, which can exacerbate other post-injury symptoms, including fatigue, impaired cognition, depression, anxiety, and pain. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a manualized treatment that effectively treats insomnia with secondary effects on cognition, mood, and pain in various populations. This paper reviews the use of CBT-I for three participants with TBI of different severities. Pre- and post-treatment assessments of insomnia, fatigue, depression, anxiety, and pain were conducted. Mood was further assessed at follow-up. Minimal clinically important difference (MCID) scores derived from the research literature were used to establish clinically meaningful symptom improvement on self-report questionnaires. The reduction in insomnia severity scores for all three participants were not large enough to be considered a clinically significant improvement following CBT-I, although trends toward improvement were observed. However, all participants showed clinically significant reductions in anxiety at post-treatment; the effects persisted for 2 participants at follow-up. Reductions in depression symptoms were observed for 2 participants at post-treatment, and treatment effects persisted for 1 participant at follow-up. One participant endorsed clinically significant improvements in fatigue and pain severity. We conclude that CBT-I may provide secondary benefits for symptoms commonly experienced by individuals with TBI, especially mood disturbances.


Decline of height with age in adults in a general population sample: estimating maximum height and distinguishing birth cohort effects from actual loss of stature with aging.
The decline in stature with age among adults is well documented. Although part of this represents a birth cohort effect, actual height declines among older individuals are known to contribute to the effect. In this study we used longitudinal changes in the heights of adults in a general population sample to determine the rate of decline in height over time in individuals of different ages. This allowed an estimation of the age at which decline in height begins, a value close to age 40 in both sexes. It also allowed derivation of equations from which the maximum height of subjects can be estimated on the basis of their sex, current height, and age. These equations should prove useful when examining the effect of aging per se on physiological measurements that are height dependent. The data also allow one to compare the magnitude of the effect of year of birth with that of the actual decline in height seen among the elderly. We estimate that approximately 60% of the smaller stature of older male subjects and 45% of the smaller stature of older female subjects is a birth cohort effect deriving from the secular trend toward greater stature; the remainder is a result of an actual decrement in height after the age of 40.


An exposure-free tool for monitoring adult malaria mosquito populations.
Catches of Anopheles gambiae and An. arabiensis with the Ifakara Tent Trap-model B (ITT-B) correlate better with human landing catches than any other method but fail to reduce the proportion of blood-fed mosquito caught, which indicates that users are exposed to bites during collection. An improved C model (ITT-C) was developed and evaluated by comparing with ITT-B in semi-field and full-field conditions in southern Tanzania. The sensitivity of the ITT-C was approximately two times that of the ITT-B: relative rate (95% confidence interval) = 1.92 (1.52-2.42), 1.90 (1.48-2.43), and 2.30 (1.54-3.30) for field populations of An. arabiensis, Culex spp., and Mansonia spp., respectively. The ITT-C caught 73% less blood-fed An. arabiensis than the ITT-B in open field experiments and none in semi-field experiments, which confirmed that the C design is a safe trapping method. Validation of ITT-C by comparison with human landing catches and parasitologic measures of human infection status may be necessary to confirm that this design produces consistent and epidemiologically meaningful results.


Solid Tumor Immunotherapy with T Cell Engager-Armed Oncolytic Viruses.
Oncolytic viruses (OVs) are novel anticancer agents that combine direct cancer cell killing with the stimulation of antitumor immunity. In addition, OVs can be engineered to deliver biological therapeutics directly to tumors, offering unique opportunities to design multimodal anticancer strategies. Here, a case for arming OVs with bispecific T cell engagers (BiTEs) is put forward. BiTEs redirect the cytotoxicity of polyclonal T cells to target cells of choice, and have demonstrated efficacy against a number of hematological cancers. However, the success of BiTEs in the treatment of solid tumors appears more limited, at least in part due to: (i) poor delivery kinetics and penetration into tumors, and (ii) on-target off-tumor activity, leading to dose-limiting toxicities. Linking the production of BiTEs to OV replication provides an exciting means to restrict production to the tumor site, widen their therapeutic window, and synergize with direct oncolysis. This review summarizes progress thus far in the preclinical development of BiTE-armed OVs, and explores the possibility of cotargeting cancer cells and nontransformed stromal cells.


Anaerobic treatment of urban wastewater in membrane bioreactors: evaluation of seasonal temperature variations.
The objective of this study was to evaluate the effect of seasonal temperature variations on the anaerobic treatment of urban wastewater in membrane bioreactors (MBRs). To this aim, sludge production, energy recovery potential, chemical oxygen demand (COD) removal and membrane permeability were evaluated in a submerged anaerobic MBR fitted with industrial-scale membrane units. The plant was operated for 172 days, between summer and winter seasons. Sludge production increased and energy recovery potential decreased when temperature decreased. COD removal and membrane permeability remained nearby stable throughout the whole experimental period.


Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. To describe changes in mortality for severe sepsis with and without shock in ICU patients. Retrospective, observational study from 2000 to 2012 including 101,064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12,512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did not differ significantly between patients with severe sepsis and those with all other diagnoses (OR, 0.94 [95% CI, 0.94-0.95] vs 0.94 [95% CI, 0.94-0.94]; P = .37). The annual increase in rates of discharge to home was significantly greater in patients with severe sepsis compared with all other diagnoses (OR, 1.03 [95% CI, 1.02-1.03] vs 1.01 [95% CI, 1.01-1.01]; P < .001). Conversely, the annual increase in the rate of patients discharged to rehabilitation facilities was significantly less in severe sepsis compared with all other diagnoses (OR, 1.08 [95% CI, 1.07-1.09] vs 1.09 [95% CI, 1.09-1.10]; P < .001). In the absence of comorbidities and older age, mortality was less than 5%. In critically ill patients in Australia and New Zealand with severe sepsis with and without shock, there was a decrease in mortality from 2000 to 2012. These findings were accompanied by changes in the patterns of discharge to home, rehabilitation, and other hospitals.


Resetting the agenda for antibiotic resistance through a health systems perspective.
Although the individual and societal consequences of antibiotic resistance spiral upwards, coordinated action has not kept pace on a global scale. The COVID-19 pandemic has highlighted the need for resilient health systems and has resulted in an unprecedented rate of collaboration in scientific, medical, social, and political dimensions. The pandemic has also created a renewed awareness of the importance of infectious diseases and is a substantial entry point for reigniting the momentum towards containing the silent pandemic of antibiotic resistance. In this Viewpoint, we discuss the limitations in the current narrative on antibiotic resistance and how it could be improved, including concerted efforts to close essential data gaps. We discuss the need for capacity building and coordination at the national and global levels to strengthen the understanding of the importance of sustainable access to effective antibiotics for all health systems that could generate tangible links to current processes for global health and development.


The burden of nausea and vomiting during pregnancy: severe impacts on quality of life, daily life functioning and willingness to become pregnant again - results from a cross-sectional study.
Though nausea and vomiting is very common during pregnancy, no studies have investigated the impact of this condition on the women's daily lives in a Scandinavian population. The aim of this study was to describe the burden of nausea and vomiting during pregnancy (NVP) on global quality of life, daily life functioning and willingness to become pregnant again according to the severity of NVP symptoms. This study is a cross-sectional population-based study conducted in Norway. Pregnant women and mothers with children <1 year of age with current or prior NVP were eligible to participate. Data were collected through an anonymous on-line questionnaire accessible from November 10th, 2014 to January 31st, 2015. Severity of NVP was measured using the 24-h Pregnancy Unique Quantification of Emesis Scale (PUQE). Associations between severity of NVP, daily life functioning and willingness to become pregnant again were tested using chi-square tests. Associations with global quality of life measured in terms of the Quality of Life Scale (QOLS) were estimated using generalized linear models and reported as unstandardized regression coefficients (β) with 95% confidence intervals (CI). 712 women with NVP were included in the study. NVP was significantly associated with several characteristics, including daily life functioning, quality of life and willingness to become pregnant again. The negative impact was greater the more severe the symptoms were, although considerable adverse effects were also seen among women with mild and moderate NVP symptoms. Over one fourth of the women with severe NVP considered terminating the pregnancy due to NVP, and three in four considered not to get pregnant again. Severity of NVP remained significantly associated with reduced global quality of life when adjusting for maternal characteristics and illnesses with β (95% CI) = -10.9 (-16.9, -4.9) for severe versus mild NVP. NVP as measured by PUQE had a major impact on various aspects of the women's lives, including global quality of life and willingness to become pregnant again.


The phonological function of vowels is maintained at fundamental frequencies up to 880 Hz.
In a between-subject perception task, listeners either identified full words or vowels isolated from these words at F0s between 220 and 880 Hz. They received two written words as response options (minimal pair with the stimulus vowel in contrastive position). Listeners' sensitivity (A') was extremely high in both conditions at all F0s, showing that the phonological function of vowels can also be maintained at high F0s. This indicates that vowel sounds may carry strong acoustic cues departing from common formant frequencies at high F0s and that listeners do not rely on consonantal context phenomena for their identification performance.


Mindfulness and healing intention: concepts, practice, and research evaluation.
This paper deals with the role of the health care professional in creating an optimal healing environment (OHE), with a special focus on which inner state and way of being in the world can create a healing intention. A core thesis is that every healing effort and every healing intention starts within the health care professional. An accepting, mindful, and warm-hearted relationship with self is primary to any healing intention. Important concepts to develop such an attitude are mindfulness, love, compassion, and awareness. The concept of a healing attitude toward the self is described, as is the mirror principle that states there is symmetry between someone's relationship with the outer world and his or her inner world. The mindfulness concept is outlined through a set of mental and heart qualities. Mindfulness is strongly related to compassion, and it is compassion that serves as a source for all healing intentionality. Compassion connects the suffering of the patient with the healer's own suffering, and this emotional connection instantiates a healing relationship. The power and importance of mindfulness and compassion for healing are explored along the Frank model of nonspecific therapeutic components. This is the approach whereby a health care professional can elicit self-healing powers in patients through his or her inner attitudes. Finally, a research program and some hypotheses on how to implement and research this specific approach toward the creation of an OHE are outlined.


Self-Administered Outpatient Antimicrobial Infusion by Uninsured Patients Discharged from a Safety-Net Hospital: A Propensity-Score-Balanced Retrospective Cohort Study.
Outpatient parenteral antimicrobial therapy (OPAT) is accepted as safe and effective for medically stable patients to complete intravenous (IV) antibiotics in an outpatient setting. Since, however, uninsured patients in the United States generally cannot afford OPAT, safety-net hospitals are often burdened with long hospitalizations purely to infuse antibiotics, occupying beds that could be used for patients requiring more intensive services. OPAT is generally delivered in one of four settings: infusion centers, nursing homes, at home with skilled nursing assistance, or at home with self-administered therapy. The first three-termed healthcare-administered OPAT (H-OPAT)--are most commonly used in the United States by patients with insurance funding. The fourth--self-administered OPAT (S-OPAT)--is relatively uncommon, with the few published studies having been conducted in the United Kingdom. With multidisciplinary planning, we established an S-OPAT clinic in 2009 to shift care of selected uninsured patients safely to self-administration of their IV antibiotics at home. We undertook this study to determine whether the low-income mostly non-English-speaking patients in our S-OPAT program could administer their own IV antimicrobials at home with outcomes as good as, or better than, those receiving H-OPAT. Parkland Hospital is a safety-net hospital serving Dallas County, Texas. From 1 January 2009 to 14 October 2013, all uninsured patients meeting criteria were enrolled in S-OPAT, while insured patients were discharged to H-OPAT settings. The S-OPAT patients were trained through multilingual instruction to self-administer IV antimicrobials by gravity, tested for competency before discharge, and thereafter followed at designated intervals in the S-OPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. The primary outcome was 30-d all-cause readmission, and the secondary outcome was 1-y all-cause mortality. The study was adequately powered for readmission but not for mortality. Clinical, sociodemographic, and outcome data were collected from the Parkland Hospital electronic medical records and the US census, constituting a historical prospective cohort study. We used multivariable logistic regression to develop a propensity score predicting S-OPAT versus H-OPAT group membership from covariates. We then estimated the effect of S-OPAT versus H-OPAT on the two outcomes using multivariable proportional hazards regression, controlling for selection bias and confounding with the propensity score and covariates. Of the 1,168 patients discharged to receive OPAT, 944 (81%) were managed in the S-OPAT program and 224 (19%) by H-OPAT services. In multivariable proportional hazards regression models controlling for confounding and selection bias, the 30-d readmission rate was 47% lower in the S-OPAT group (adjusted hazard ratio [aHR], 0.53; 95% CI 0.35-0.81; p = 0.003), and the 1-y mortality rate did not differ significantly between the groups (aHR, 0.86; 95% CI 0.37-2.00; p = 0.73). The S-OPAT program shifted a median 26 d of inpatient infusion per patient to the outpatient setting, avoiding 27,666 inpatient days. The main limitation of this observational study-the potential bias from the difference in healthcare funding status of the groups-was addressed by propensity score modeling. S-OPAT was associated with similar or better clinical outcomes than H-OPAT. S-OPAT may be an acceptable model of treatment for uninsured, medically stable patients to complete extended courses of IV antimicrobials at home.


Results after sacral nerve stimulation for chronic constipation.
Sacral nerve stimulation is an established treatment for fecal incontinence and initial reports describe successful results also in subjects with chronic constipation. Consecutive patients with slow transit or outlet obstruction type constipation were offered external stimulation through a test electrode inserted in a sacral foramen during a 3-week period. The symptomatic evaluation was based on the number of bowel movements and a validated obstructed defecation score (ODS). A permanent implant was performed provided an overall 50% decrease in symptoms was observed. In total, 44 patients with chronic constipation were treated with a 3-week test stimulation. Fifteen experienced a 50% reduction of symptoms and received a permanent implant. Four of the 15 with permanent implants were explanted during the course of the study. Five subjects (11% of original group) reported sustained symptom relief at final follow-up after a mean of 24 months (range 4-81). Mean ODS score did not change during the treatment. Patients with predominantly slow transit constipation or outlet obstruction did not differ concerning success rate. Sacral nerve stimulation has limited efficacy in unselected patients with chronic constipation and cannot be recommended for treatment on routine basis.


Radiation Tolerance of Pseudanabaena catenata, a Cyanobacterium Relevant to the First Generation Magnox Storage Pond.
Recently a species of Pseudanabaena was identified as the dominant photosynthetic organism during a bloom event in a high pH (pH ∼11.4), radioactive spent nuclear fuel pond (SNFP) at the Sellafield Ltd., United Kingdom facility. The metabolic response of a laboratory culture containing the cyanobacterium Pseudanabaena catenata, a relative of the major photosynthetic microorganism found in the SNFP, to X-ray irradiation was studied to identify potential survival strategies used to support colonization of radioactive environments. Growth was monitored and the metabolic fingerprints of the cultures, during irradiation and throughout the post-irradiation recovery period, were determined using Fourier transform infrared (FT-IR) spectroscopy. A dose of 95 Gy delivered over 5 days did not significantly affect growth of P. catenata, as determined by turbidity measurements and cell counts. Multivariate statistical analysis of the FT-IR spectral data revealed metabolic variation during the post-irradiation recovery period, with increased polysaccharide and decreased amide spectral intensities. Increases in polysaccharides were confirmed by complementary analytical methods including total carbohydrate assays and calcofluor white staining. This observed increased production of polysaccharides is of significance, since this could have an impact on the fate of the radionuclide inventory in the pond via biosorption of cationic radionuclides, and may also impact on downstream processes through biofilm formation and biofouling.


Visualization of the in vivo generation of donor antigen-specific effector CD8+ T cells during mouse cardiac allograft rejection: in vivo effector CD8+ T cell generation during allograft rejection.
An adoptive transfer system was used to study the fate of alloreactive CD8+ H-2Kb-specific TCR transgenic (DES+) T cells in vivo after transplantation. A trace population of 2.0x10(6) CD8+DES+ T cells were adoptively transferred into syngeneic CBA.Ca (H-2k) mice 24 hr before transplantation of an H-2Kb+ or H-2Kb- cardiac allograft. H-2Kb specific T cells proliferated and produced interleukin-2 and interferon-gamma in response to H-2Kb+, but not H-2Kb- cardiac allografts. CD8+DES+ T cells that infiltrated the H-2Kb+ cardiac allografts developed a distinct cell surface and cytokine phenotype compared with the CD8+DES+ T cells that remained in the periphery. H-2Kb-specific graft infiltrating T cells (a) underwent a larger number of cell divisions (> =3), (b) increased in size, (c) up-regulated CD69, and (d) down-regulated CD62L. These results demonstrate that alloantigen-specific T cells can be monitored in vivo during the immune response to an allograft and that the fate of CD8+ T cells specific for the allogeneic class I molecules expressed by the graft is different between cells in the periphery and those that infiltrate the graft.


Omega-3 Fatty Acid Intake of Pregnant Women and Women of Childbearing Age in the United States: Potential for Deficiency?
Omega-3 fatty acids play critical roles during fetal growth and development with increased intakes associated with improved maternal-fetal outcomes. Omega-3 fatty acid intake in Western diets is low, and the impact of socioeconomic factors on omega-3 fatty acid intake in pregnant women and women of childbearing age has not been reported. We used the National Health and Nutrition Examination Survey (NHANES) cycles 2003-2012 to assess the relationship between omega-3 fatty acid intake and socioeconomic factors in women of childbearing age. Out of 7266 eligible participants, 6478 were women of childbearing age, while 788 were identified as pregnant at the time of the survey. Mean EPA+DHA intake of the population was 89.0 mg with no significant difference between pregnant and non-pregnant women. By univariate and multivariate analyses adjusting for confounders, omega-3 fatty acid intake was significantly associated with poverty-to-income ratio, race, and educational attainment. Our results demonstrate that omega-3 fatty acid intake is a concern in pregnant women and women of childbearing age in the United States, and that socioeconomically disadvantaged populations are more susceptible to potential deficiencies. Strategies to increase omega-3 fatty acid intake in these populations could have the potential to improve maternal and infant health outcomes.


Species or Genotypes? Reassessment of Four Recently Described Species of the Ceratocystis Wilt Pathogen, Ceratocystis fimbriata, on Mangifera indica.
Ceratocystis wilt is among the most important diseases on mango (Mangifera indica) in Brazil, Oman, and Pakistan. The causal agent was originally identified in Brazil as Ceratocystis fimbriata, which is considered by some as a complex of many cryptic species, and four new species on mango trees were distinguished from C. fimbriata based on variation in internal transcribed spacer sequences. In the present study, phylogenetic analyses using DNA sequences of mating type genes, TEF-1α, and β-tubulin failed to identify lineages corresponding to the four new species names. Further, mating experiments found that the mango isolates representing the new species were interfertile with each other and a tester strain from sweet potato (Ipomoea batatas), on which the name C. fimbriata is based, and there was little morphological variation among the mango isolates. Microsatellite markers found substantial differentiation among mango isolates at the regional and population levels, but certain microsatellite genotypes were commonly found in multiple populations, suggesting that these genotypes had been disseminated in infected nursery stock. The most common microsatellite genotypes corresponded to the four recently named species (C. manginecans, C. acaciivora, C. mangicola, and C. mangivora), which are considered synonyms of C. fimbriata. This study points to the potential problems of naming new species based on introduced genotypes of a pathogen, the value of an understanding of natural variation within and among populations, and the importance of phenotype in delimiting species.


Food Safety Perceptions and Practices among Smallholder Pork Value Chain Actors in Hung Yen Province, Vietnam.
Pork safety is an important public health concern in Vietnam and is a shared responsibility among many actors along the pork value chain. We examined the knowledge, perceptions, and practices regarding food safety, disease, and health risk among selected pork value chain actors (slaughterhouse owners and workers, people living around slaughterhouses, pork sellers, consumers, and veterinary and public health staff) in three districts in Hung Yen Province, Vietnam. We randomly selected 52 pork value chain actors to be surveyed through questionnaires, observation checklists, key informant interviews, and focus group discussions. Most slaughterhouse workers acquired knowledge and experience of food safety through "learning by doing" rather than from training by a veterinary or public health professional. Both slaughterhouse worker and pork seller groups had some accurate perceptions about pig diseases and foodborne diseases; however, misperceptions of risk and, especially, of zoonoses were present. Furthermore, while workers and sellers often use cloths to dry the meat and clean equipment, they did not think this was a risk for meat contamination. Moreover, when sellers wear protective equipment, such as gloves, masks, or hats, consumers perceive that the sellers may have health issues they are trying to conceal and so consumers avoid buying from them. The perceived freshness of pork, along with trust in the seller and in the pork production process, were strong indicators of consumer preference. And yet, pork value chain actors tend to trust their own individual food safety practices more, rather than the practices of other actors along the chain. Veterinary and public health staff emphasized the gap between regulations and food safety practices. Education and training on food safety risks and proper handling are priorities, along with integrated and intensive efforts to improve food safety among pork value chain actors.


Cerebral glucose deficiency versus oxygen deficiency in neonatal encephalopathy.
Hypoxic-ischemic encephalopathy (HIE) in newborn infants is generally considered to result from decreased arterial oxygen content or cerebral blood flow. Cerebral injury similar to that of HIE has been noted with hypoglycemia. Studies in fetal lambs have shown that ventilation with 3% oxygen did not change cerebral blood flow, but ventilation with 100% oxygen resulted in marked reduction in cerebral blood flow, glucose delivery and glucose consumption. Blood glucose concentration falls markedly after birth; this, associated with the fall in cerebral blood flow, greatly reduces glucose supply to the brain. In preterm infants, blood glucose levels tend to be very low. Also persistent patency of the ductus arteriosus may reduce cerebral flow in diastole, thus exaggerating the decrease in glucose supply. I propose that glycopenic-ischemic encephalopathy is a more appropriate term for the cerebral insult. We should consider more aggressive management of the low blood glucose concentrations in the neonate, and particularly in preterm infants. Administration of high levels of oxygen in inspired air should be avoided to reduce the enhancement of cerebral vasoconstriction and decreased flow that normally occurs after birth.


Neurocognitive Recovery of Sentence Processing in Aphasia.
Purpose Reorganization of language networks in aphasia takes advantage of the facts that (a) the brain is an organ of plasticity, with neuronal changes occurring throughout the life span, including following brain damage; (b) plasticity is highly experience dependent; and (c) as with any learning system, language reorganization involves a synergistic interplay between organism-intrinsic (i.e., cognitive and brain) and organism-extrinsic (i.e., environmental) variables. A major goal for clinical treatment of aphasia is to be able to prescribe treatment and predict its outcome based on the neurocognitive deficit profiles of individual patients. This review article summarizes the results of research examining the neurocognitive effects of psycholinguistically based treatment (i.e., Treatment of Underlying Forms; Thompson & Shapiro, 2005) for sentence processing impairments in individuals with chronic agrammatic aphasia resulting from stroke and primary progressive aphasia and addresses both behavioral and brain variables related to successful treatment outcomes. The influences of lesion volume and location, perfusion (blood flow), and resting-state neural activity on language recovery are also discussed as related to recovery of agrammatism and other language impairments. Based on these and other data, principles for promoting neuroplasticity of language networks are presented. Conclusions Sentence processing treatment results in improved comprehension and production of complex syntactic structures in chronic agrammatism and generalization to less complex, linguistically related structures in chronic agrammatism. Patients also show treatment-induced shifts toward normal-like online sentence processing routines (based on eye movement data) and changes in neural recruitment patterns (based on functional neuroimaging), with posttreatment activation of regions overlapping with those within sentence processing and dorsal attention networks engaged by neurotypical adults performing the same task. These findings provide compelling evidence that treatment focused on principles of neuroplasticity promotes neurocognitive recovery in chronic agrammatic aphasia. Presentation Videohttps://doi.org/10.23641/asha.10257587.


Attitudes to physical healthcare in severe mental illness; a patient and mental health clinician qualitative interview study.
People with severe mental illness experience physical health significantly worse than the general population. Physical health monitoring is shared between primary care and secondary mental healthcare services, though there is debate whether mental health teams should provide more physical healthcare. The views of mental health clinicians and patients with mental illness towards physical healthcare provision are unclear. To explore the attitudes of Community Mental Health Team (CMHT) clinicians and patients experiencing severe mental illness towards physical healthcare and its provision. Qualitative study in a CMHT setting. Interviews were carried out with CMHT clinicians and patients with severe mental illness. Data were collected using semi-structured interviews and analysed using thematic analysis. There were 14 patients and 15 clinicians recruited. Patients varied in their awareness of the association between physical and mental health, but were engaged in physical health monitoring. Clinicians were aware of the importance of physical healthcare but reported barriers to provision, including lack of training, resource constraints and uncertainty in their role. There was no consensus in either group regarding how physical healthcare should be provided, with diverse attitudes expressed for why CMHTs should and shouldn't provide more physical healthcare. Increasing physical healthcare provision from mental health teams requires healthcare-related barriers be addressed, but it remains unclear whether CMHT clinicians or patients believe this to be a solution.


Size-dependent surface plasmon resonance in silver silica nanocomposites.
Silver silica nanocomposites were obtained by the sol-gel technique using tetraethyl orthosilicate (TEOS) and silver nitrate (AgNO(3)) as precursors. The silver nitrate concentration was varied for obtaining composites with different nanoparticle sizes. The structural and microstructural properties were determined by x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). X-ray photoelectron spectroscopic (XPS) studies were done for determining the chemical states of silver in the silica matrix. For the lowest AgNO(3) concentration, monodispersed and spherical Ag crystallites, with an average diameter of 5 nm, were obtained. Grain growth and an increase in size distribution was observed for higher concentrations. The occurrence of surface plasmon resonance (SPR) bands and their evolution in the size range 5-10 nm is studied. For decreasing nanoparticle size, a redshift and broadening of the plasmon-related absorption peak was observed. The observed redshift and broadening of the SPR band was explained using modified Mie scattering theory.


Language status at age 3: Group and individual prediction from vocabulary comprehension in the second year.
The present research extends recent work on the prediction of preschool language skills by exploring prediction from decontextualized vocabulary comprehension. Vocabulary comprehension was a stronger predictor than parent-reported production, yielding a quadrupling of variance accounted for relative to prior studies. Parallel studies (Studies 1 and 2) are reported for two linguistically and geographically distinct samples. In both samples, decontextualized vocabulary comprehension late in the second year provided the best balance between model fit and parsimony in predicting language skills at age three. In Study 3, vocabulary comprehension prospectively identified children with low language status 2 years earlier than other prospective studies but with similar sensitivity and specificity. The present paper provides evidence on three questions of practical and theoretical significance: the relation between decontextualized vocabulary prior to 30 months of age and language outcomes, how prediction from decontextualized vocabulary compares with parent-reported vocabulary, and finally how early stable predictions to language outcomes can be made. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Prevalence and clinical characteristics of obstructive- and central-dominant sleep apnea in candidates of catheter ablation for atrial fibrillation in Japan.
We aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. Before catheter ablation, 197 consecutive AF patients (age: 60 ± 9 years, body mass index; 25.0 ± 3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. The mean apnea-hypopnea index (AHI) was 17.7 ± 11.9, with 135 AF patients having an AHI ≥10 (68.5%). Patients with an AHI ≥10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI ≥10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, P = 0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. The prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.


Ethical issues in rural nursing practice in Botswana.
The concern for ethical principles and values is not limited to health professionals alone. However, ethical principles in nursing act as safety valves for social control to prevent professional misconduct and abuse of the rights of clients. As a result of colonial experience, developing countries like Botswana usually follow the European lead, especially examples from the UK. This article examines the ethical problems and dilemmas associated with rural nursing practice in Botswana, a developing country in sub-Saharan Africa. The major ethical problems identified are related to the distribution of and access to health resources in rural communities. It is proposed that nurses must assume responsibility in the field of access and allocation by working collaboratively with governments and other professional bodies, and that nurses as a global community must work together as a team to support each other.


Age-Specific Injury Risk Curves for Distributed, Anterior Thoracic Loading of Various Sizes of Adults Based on Sternal Deflections.
Injury Risk Curves are developed from cadaver data for sternal deflections produced by anterior, distributed chest loads for a 25, 45, 55, 65 and 75 year-old Small Female, Mid-Size Male and Large Male based on the variations of bone strengths with age. These curves show that the risk of AIS ≥ 3 thoracic injury increases with the age of the person. This observation is consistent with NASS data of frontal accidents which shows that older unbelted drivers have a higher risk of AIS ≥ 3 chest injury than younger drivers.


Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent.
Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into cancer angiogenesis, and thus potentially improve cancer diagnosis and management.


The protective effects of a polyphenol-enriched protein powder on exercise-induced susceptibility to virus infection.
Prolonged and intensive exercise induces transient immunosuppression and is associated with an increased risk and severity of infections. The goal of this study was to characterize the antiviral and antibacterial properties of the bioactive metabolites of a blueberry-green tea-polyphenol soy protein complex (PSPC) in the serum of supplemented subjects during a 3-day intensified training period. Long-distance runners, randomly divided into two groups, ingested 40 g/day PSPC or placebo (soy protein and colorings) for 17 days, with a 3-day running period inserted at day 14. Blood serum samples were collected pre-14 days and post-14 days supplementation, and immediately and 14 h after the third day of running. The post-exercise serum from both groups significantly promoted the growth of Escherichia coli and Staphylococcus aureus in culture by 20-70%, but returned to normal levels following recovery. Furthermore, the serum from subjects ingesting PSPC did not display antibacterial properties at any time point. In contrast, there was a significant difference in the ability of serum from PSPC-supplemented versus placebo-supplemented athletes to protect cells in culture from killing by vesicular stomatitis virus following strenuous exercise. In addition, the serum of subjects who ingested PSPC significantly delayed an exercise-induced increase in virus replication. These results indicate that polyphenol complexes containing blueberry and green tea have the potential to protect athletes from virus infections following rigorous exercise.


Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use.
Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.


Ethnic variation in the activity of lipid desaturases and their relationships with cardiovascular risk factors in control women and an at-risk group with previous gestational diabetes mellitus: a cross-sectional study.
Lipid desaturase enzymes mediate the metabolism of fatty acids to long chain polyunsaturated fatty acids and their activities are related to metabolic risk factors for Type 2 diabetes (T2DM) and coronary heart disease (CHD). There are marked ethnic differences in risks of CHD and T2DM but little is known about ethnic differences in desaturase activities. Samples from a study of CVD risk in women with previous gestational diabetes were analysed for percentage fatty acids in plasma free fatty acid, triglyceride, cholesterol ester and phospholipid pools for 89 white European, 53 African Caribbean and 56 Asian Indian women. The fatty acid desaturase activities, stearoyl-CoA desaturase (SCD, calculated separately for C16 and C18 fatty acids), delta 6 desaturase (D6D) and delta 5 desaturase (D5D) were estimated from precursor-to-product ratios and their relationships with adiposity, blood pressure, cholesterol, triglycerides, HDL cholesterol and insulin sensitivity explored. Ethnic differences in desaturase activities independent of ethnic variation in risk factor correlates of desaturase activities were then identified. There was significant ethnic variation in age, BMI, waist circumference, blood pressure, serum triglycerides and HDL cholesterol concentrations and insulin resistance. Desaturase activities showed significant correlations, independent of ethnicity, with BMI, waist circumference, triglycerides and HDL cholesterol. Independent of ethnic variation in BMI, waist circumference, triglycerides and HDL cholesterol, SCD-16 activity, calculated from each of the four lipid pools measured, was 18-35 percent higher in white Europeans than in African Caribbeans or Asian Indians (all p < 0.001). Similar, though less consistent differences were apparent for SCD-18 activity. Also independently of risk factor variation, but specifically when calculated from the cholesterol ester and phospholipid, pools, D6D activity was significantly lower in Asian Indians, and D5D activity higher in African Caribbeans. Significant ethnic differences exist in desaturase activities, independently of ethnic variation in other risk factors. These characteristics did not accord with higher risk of T2DM among African Caribbeans and Asian Indians nor with lower risk of CHD among African Caribbeans but did accord with the higher risk of CHD in Asian Indians.


Strain variation of bacillus Calmette-Guerin-induced pulmonary granuloma formation is correlated with anergy and the local production of migration inhibition factor and interleukin 1.
Pulmonary granulomatous inflammation was induced by the intratracheal injection of viable bacillus Calmette-Guerin (BCG) into genetically high granuloma responder (C57BL/6J and BALB/c) and low responder (CBA/J) mice with and without immunization by methylated bovine serum albumin in complete Freund's adjuvant. Significant migration inhibition factor (MIF) and interleukin 1 (IL 1) activities were detected in aqueous lung granuloma extracts prepared from high responder mice bearing BCG-induced granulomatous inflammation. Interleukin 2 activity was not detected. Very low MIF and IL 1 activities were detected in extracts from low responder mice. Furthermore, high responder, but not low responder, mice showed marked suppression of in vivo and in vitro manifestations of cell-mediated immunity to both specific and nonspecific antigens. In contrast, humoral antibody response was not affected significantly. The kinetics of anergy in granuloma-bearing mice correlated closely with the appearance of MIF and IL 1 activities in the lesions. Thus, genetically determined granuloma response to BCG and the expression of anergy in various strains of mice were well associated with in vivo release of MIF and IL 1. These results indicate that the genetic ability or inability to mount a granulomatous inflammatory response to BCG may extend to the capacity of cells within the lesions to generate soluble mediator(s) which is also responsible for anergy in granuloma-bearing mice.


Enteral fish oil in critical illness: perspectives and systematic review.
To summarize recent research addressing the role of enteral fish oil supplementation in critical illness. A number of new multicenter trials examining both the use of fish oil given as a supplement to enteral nutrition support and given as a separate bolus, independent of nutrition delivery, have recently been reported. Mechanistic data suggest that administration of fish oil may help attenuate the systemic inflammatory response and allow for appropriate resolution of inflammation in critically ill patients. Recent data indicate that enteral fish oil given as a continuous infusion as part of complete nutrition improves outcome in critically ill patients, especially those with acute lung injury/acute respiratory distress syndrome. In contrast, the bolus administration of fish oil cannot be recommended as clinically beneficial in acute lung injury/acute respiratory distress syndrome patients. Recent trials indicate that pharmacologically administered nutrients should be studied in the same manner as other new drugs, with appropriate attention to early dosing trials, proper pre-enrollment patient selection, and understanding of the role of concomitant protein/calorie nutrition. More research continues to be needed to optimize the proper patient, dose, and timing of administration for enteral fish oil therapy in the ICU.


Cloning and sequencing of the low-affinity penicillin-binding protein 3r-encoding gene of Enterococcus hirae S185: modular design and structural organization of the protein.
The clinical isolate Enterococcus hirae S185 has a peculiar mode of resistance to penicillin in that it possesses two low-affinity penicillin-binding proteins (PBPs): the 71-kDa PBP5, also found in other enterococci, and the 77-kDa PBP3r. The two PBPs have the same low affinity for the drug and are immunochemically related to each other. The PBP3r-encoding gene has been cloned and sequenced, and the derived amino acid sequence has been compared by computer-assisted hydrophobic cluster analysis with that of the low-affinity PBP5 of E. hirae R40, the low-affinity PBP2' of Staphylococcus aureus, and the PBP2 of Escherichia coli used as the standard of reference of the high-M(r) PBPs of class B. On the basis of the shapes, sizes, and distributions of the hydrophobic and nonhydrophobic clusters along the sequences and the linear amino acid alignments derived from this analysis, the dyad PBP3r-PBP5 has an identity index of 78.5%, the triad PBP3r-PBP5-PBP2' has an identity index of 29%, and the tetrad PBP3r-PBP5-PBP2'-PBP2 (of E. coli) has an identity index of 13%. In spite of this divergence, the low-affinity PBPs are of identical modular design and possess the nine amino acid groupings (boxes) typical of the N-terminal and C-terminal domains of the high-M(r) PBPs of class B. At variance with the latter PBPs, however, the low-affinity PBPs have an additional approximately 110-amino-acid polypeptide stretch that is inserted between the amino end of the N-terminal domain and the carboxy end of the membrane anchor. While the enterococcal PBP5 gene is chromosome borne, the PBP3r gene appears to be physically linked to the erm gene, which confers resistance to erythromycin and is known to be plasmid borne in almost all the Streptococcus spp. examined.


Expression of dominant-negative src-homology domain 2-containing protein tyrosine phosphatase-1 results in increased Syk tyrosine kinase activity and B cell activation.
The Src-homology domain 2 (SH2)-containing cytoplasmic tyrosine phosphatase, SHP-1 (SH2-containing protein tyrosine phosphatase-1), interacts with several B cell surface and intracellular signal transduction molecules through its SH2 domains. Mice with the motheaten and viable motheaten mutations are deficient in SHP-1 and lack most mature B cells. To define the role of SHP-1 in mature B cells, we expressed phosphatase-inactive SHP-1 (C453S) in a mature B cell lymphoma line. SHP-1 (C453S) retains the ability to bind to both substrates and appropriate tyrosine-phosphorylated proteins and therefore can compete with the endogenous wild-type enzyme. We found that B cells expressing SHP-1 (C453S) demonstrated enhanced and prolonged tyrosine phosphorylation of proteins with molecular masses of 110, 70, and 55-60 kDa after stimulation with anti-mouse IgG. The tyrosine kinase Syk was hyperphosphorylated and hyperactive in B cells expressing SHP-1 (C453S). SHP-1 and Syk were coimmunoprecipitated from wild-type K46 cells, K46 SHP-1 (C453S) cells, and splenic B cells, and SHP-1 dephosphorylated Syk. Cells expressing SHP-1 (C453S) showed increased Ca2+ mobilization, extracellular signal-regulated kinase activation, and homotypic adhesion after B cell Ag receptor engagement. Thus, SHP-1 regulates multiple early and late events in B lymphocyte activation.


G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60c-src and p21ras.
The binding of vasoactive peptides to their respective G protein-coupled receptors has been implicated in the pathogenesis of vascular smooth muscle cell proliferation, leading to the development of hypertension, arteriosclerosis, and restenosis after vascular injury. We previously showed that the cytosolic tyrosine kinase pp60c-src is crucial for angiotensin II (ANG II)-induced activation of the protooncogene p21ras. Therefore, we investigated the role of pp60c-src and p21ras in rat aortic smooth muscle cell proliferation induced by several G protein-coupled receptors. ANG II, endothelin-1, or thrombin increased cell proliferation and DNA synthesis. Electroporation of anti-pp60c-src antibodies into cells abolished proliferation in response to these G protein-coupled receptor ligands but not in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, electroporation of anti-p21ras antibody completely blocked DNA synthesis and cell proliferation in response to ANG II, endothelin-1, thrombin, and PDGF-BB. Our data indicate that the pp60c-src tyrosine kinase is necessary and specific for vascular smooth muscle cell proliferation and DNA synthesis in response to G protein-coupled receptors but not classic growth factor receptors.


Body mass index and dental caries in New Zealand pre-school children: A population-based study.
Pre-school dental caries is a significant public health problem and may be associated with the growth and nutritional status of children. This study aimed to investigate the association between body mass index (BMI) and early childhood caries (ECC) among pre-school children. This population-based retrospective study involves all 5-year-old children who resided in northern New Zealand and received school entry dental examinations between 1 January 2014 and 31 December 2015. ECC status was determined with the decayed missing filled teeth (dmft) score obtained from a routinely collected regional dental data set. Objectively measured BMI information was obtained from the 'Before School Check' (B4SC) Programme. Logistic regression analyses were used to assess the association between BMI and the occurrence of ECC (dmft score ≥ 1). Ethnic subgroup analyses were also conducted. Of the 27 333 children involved in this analysis, 11 173 (40.9%) had ECC with a mean dmft score of 1.85, and 3948 (14.4%) were overweight and 2964 (10.8%) were obese at school entry. The prevalence of ECC was higher in overweight and obese children but in subgroup analyses by ethnicity, this positive association was observed in European children only (adjusted odds ratio for overweight children compared to normal weight children: 1.16; 95% CI: 1.02, 1.32 and adjusted odds ratio for obese children: 1.20; 95% CI: 1.00, 1.45). ECC is highly prevalent in New Zealand children and associated with higher BMI in children of European ethnicity.


Clinical learning environment, supervision and nurse teacher evaluation scale: psychometric evaluation of the Swedish version.
This article is a report of the development and psychometric testing of the Swedish version of the Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale. To achieve quality assurance, collaboration between the healthcare and nursing systems is a pre-requisite. Therefore, it is important to develop a tool that can measure the quality of clinical education. The Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale is a previously validated instrument, currently used in several universities across Europe. The instrument has been suggested for use as part of quality assessment and evaluation of nursing education. The scale was translated into Swedish from the English version. Data were collected between March 2008 and May 2009 among nursing students from three university colleges, with 324 students completing the questionnaire. Exploratory factor analysis was performed on the 34-item scale to determine construct validity and Cronbach's alpha was used to measure the internal consistency. The five sub-dimensions identified in the original scale were replicated in the exploratory factor analysis. The five factors had explanation percentages of 60.2%, which is deemed sufficient. Cronbach's alpha coefficient for the total scale was 0.95, and varied between 0.96 and 0.75 within the five sub-dimensions. The Swedish version of Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale has satisfactory psychometric properties and could be a useful quality instrument in nursing education. However, further investigation is required to develop and evaluate the questionnaire.


Biomimic strategies for modulating the interaction between particle adjuvants and antigen-presenting cells.
Developing effective adjuvants is becoming increasingly important for the research of vaccine formulations. The addition of adjuvants could enhance the immune response, reduce the antigen dosage and prolong the protection time. In recent years, biomimetic strategies have been adopted in the design of vaccine adjuvants to achieve better immune protection efficiency. Particularly those particle adjuvants, which could easily mimic the physical and chemical properties of natural pathogens such as morphology and charge, have been developed. This review focuses on the study of bionic particle adjuvants, especially the effect of those particles' properties on their interaction with antigen-presenting cells (APCs). By mimicking natural pathogens, these particles possess the ability to increase the cellular uptake of antigens, activate APCs, and promote the lysosomal escape of antigens.


[Contact, epidemics, and the body as agents of change: a study of AIDS among the Xokléng indians in the State of Santa Catarina, Brazil].
Based on an analysis of AIDS cases among the Xokléng Indians in 1988, this article relates the illness phenomenon to socio-cultural disruptions and transformations in this indigenous group's universe, focusing on the history of their contact with Brazilian national society. The analysis and interpretation of this relationship are based on anthropological theories about the centrality of the body, corporeality, and degenerative bodily processes in Brazilian indigenous societies, according to which the body, society, and macro-situational elements are articulated by social praxis, and should thus be related in socio-anthropological studies of health-illness phenomena. The article briefly describes the history of epidemics emerging from contact and attempts to relate them to specific historical contexts. Ethnomedical categories, cosmology, and Xokléng concepts of corporeality are related to their social organization, which are thus connected to the AIDS cases. The latter are presented with a special focus on the relationship between their emergence and the changes occurring in the Xokléng world with the construction of a dam bordering on their land.


Why do species vary in their rate of molecular evolution?
Despite hopes that the processes of molecular evolution would be simple, clock-like and essentially universal, variation in the rate of molecular evolution is manifest at all levels of biological organization. Furthermore, it has become clear that rate variation has a systematic component: rate of molecular evolution can vary consistently with species body size, population dynamics, lifestyle and location. This suggests that the rate of molecular evolution should be considered part of life-history variation between species, which must be taken into account when interpreting DNA sequence differences between lineages. Uncovering the causes and correlates of rate variation may allow the development of new biologically motivated models of molecular evolution that may improve bioinformatic and phylogenetic analyses.


Serum Lipid Levels and Risk Of Hand Osteoarthritis: The Chingford Prospective Cohort Study.
The development of hand osteoarthritis (HOA) could be linked to hyperlipidaemia. No longitudinal studies have addressed the relationship between serum lipid profile and HOA. The study aim was to determine the association between serum lipid profile and the incidence of radiographic hand osteoarthritis (RHOA). All women in a prospective population-based cohort from the Chingford study with available baseline lipid measurements and without RHOA on a baseline were included. Study outcome was the incidence of RHOA in year 11 of follow-up. Serum lipid profile variables were analysed as continuous variables and categorised into quartiles. The association between serum lipid profile and RHOA was modeled using multivariable logistic regression. Overall RHOA incidence was 51.6% (45.7-57.4%). An inverse association between HDL cholesterol levels and the incidence of RHOA was observed by quartile: OR of 0.36 [95%CI 0.17-0.75], 0.52 [95%CI 0.26-1.06], and 0.48 [95%CI 0.22-1.03]. Triglycerides levels showed a significant trend. No relationship was found with total or LDL cholesterol. Higher levels of HDL cholesterol appear to protect against RHOA after 11 years of follow-up. More research is needed to elucidate HOA risk factors, the mechanisms related to the lipid pathway, and the effects of lipid-lowering agents on reducing the incidence of OA.


Sustained-release delivery of octreotide from biodegradable polymeric microspheres.
The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR(®) formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague-Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR(®) all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40-130 pg/10 μL and 20-100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR(®) every 28 days and every 42 days at a dose of 3 mg/rat, respectively.


Status of serum magnesium in Egyptian children with type 1 diabetes and its correlation to glycemic control and lipid profile.
Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency, having 25% to 39% prevalence. This deficit could be associated with the development of late diabetic complications, especially macroangiopathy.We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assess its relation to glycemic control and lipid profile.We included 71 Egyptian children with type 1diabetes having their follow-up at Pediatric Endocrinology outpatient clinic, Zagazig University Hospital and 71 age- and sex-matched control. We measured Serum magnesium, HbA1c, and lipid profile in all study subjects.Diabetic children had significantly lower serum magnesium level compared to control children (1.83 ± .27 mg/dL in diabetic children versus 2.00 ± .16 mg/dL in control children). Taking cut-off level of serum magnesium <1.7 mg/dL for definition of hypomagnesemia, hypomagnesemia was detected in 28.2% of diabetic children compared to 9.9% of control children. In diabetic patients, there was statistically significant difference in HbA1c between hypomagnesemic and normomagnesemic group being higher in the low magnesium group, as it is mean ± SD was 11.93 ± 3.17 mg/dL in group I versus 8.92 ± 0.93 mg/dL in the normomagnesemic group. Serum magnesium was found to be positively correlated with HDL (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, LDL, and duration of diabetes (P < 0.001).We concluded that total serum magnesium was frequently low in Egyptian children with type 1 diabetes and it is correlated with HbA1c and with lipid profile. Hypomagnesemia was more evident in patients with poor diabetic control and those with higher atherogenic lipid parameters. We suggest that low serum magnesium may be included in pathogenesis of poor glycemic control and abnormal lipid profile in children with type 1 diabetes. We need to perform further studies on giving magnesium supplements in diabetic children with hypomagnesemia to observe the effect of correction of serum magnesium on glycemic control, lipid profile, and the risk of diabetic complications.


Phosphorproteome Changes of Myofibrillar Proteins at Early Post-mortem Time in Relation to Pork Quality As Affected by Season.
The effect of season on phosphorylation of myofibrillar proteins and meat quality of pork longissimus muscles was investigated. Muscle samples were obtained from 40 pork carcasses (10 for each season) at 45 min and 3 and 9 h post-mortem. Myofibrillar proteins were extracted, separated by SDS-PAGE, quantified by phosphor-specific staining, and finally identified by LC-MS/MS. Muscle pH, glycogen, and ATP were measured, and pale, soft, and exudative (PSE) meat was identified by pH value at 45 min post-mortem. A total of 23 bands were detected on SDS-PAGE gels. The phosphorylation levels of bands did not differ between PSE and normal meat. However, the phosphorylation levels of 22 bands were significantly changed by season. Nine of them showed different changes from 45 min to 9 h post-mortem, which were identified to be involved in energy metabolism and sarcomere contraction. Correlation analysis indicated the regulatory progress of these proteins during rigor mortis. These observations contribute to a better understanding of the biochemical processes for the conversion of muscle to meat varying with season.


Complex Female Pelvic Pain: A Case Series From a Multidisciplinary Clinic in Urogynecology and Physiatry.
The internal pelvic floor muscles that support the pelvic viscera lie within the external pelvic structures, which support posture and locomotion. The presence of pain in the hip, groin, leg, abdomen, and/or back in patients with pelvic pain suggests that external pelvic sites may act as pain generators that contribute to chronic pelvic pain (CPP). The aim of this study was to report musculoskeletal diagnoses resulting from including a physiatry evaluation as part of a Multidisciplinary Pelvic Pain Clinic for women with complex chronic pain. This retrospective case series was conducted by chart review of all women attending the clinic from February 2016 through March 2018. Variable definitions were created for each demographic and clinical characteristic and used to guide a structured review of the chart. Descriptive statistical analysis was performed. Ninety-six percent of the 68 women (mean age, 51 years) had CPP of 6 months' duration or longer. Levator ani tenderness was present in 81% and obturator internus tenderness in 81%. Seventy-one percent of women had failed pelvic physical therapy. Musculoskeletal diagnoses included osteoarthritis, tendinopathies, enthesopathies, osteitis pubis, ischiofemoral impingement, Paget disease, and other systemic conditions. Musculoskeletal abnormalities were common in this highly selected cohort of complex CPP cases with external pelvic symptoms. The imaging findings and specific diagnoses allowed targeted therapy beyond generalized physical therapy for CPP. The expertise of urogynecologists and physical therapists who evaluate the internal pelvic muscles and viscera combined with the physiatrist's expertise in musculoskeletal assessment and imaging provides an expanded, collaborative approach for managing these patients.


Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA.
We have recently shown that oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides (CpG motif) can induce B cells to proliferate, differentiate, and secrete cytokines. In this study we demonstrate that CpG motifs contained in ODN as short as 15 bases in length were quite effective at inducing NK cell lytic activity in vitro in both human and murine lymphocytes. Such ODN were also effective at inducing NK lytic activity, in vivo, in mice. Experiments designed to determine the cellular and cytokine requirements for NK cell induction revealed that B and T cells are not necessary, that the ODN do not augment the activity of highly purified NK cells, and that the ODN augment NK cell activity indirectly by inducing the secretion of IL-12, IFN-alpha beta, and TNF-alpha. Various ODN sequences were prepared to determine the optimal ODN length, motif, palindrome, backbone modification, and dose requirements. We found no requirement for a palindromic sequence but a definite requirement for an unmethylated CpG motif. While necessary, however, a CpG motif was not sufficient for NK cell induction. Instead, there appeared to be stringent requirements for the immediate flanking bases at the 5' and 3' ends as well as for flanking sequences outside the immediate 5' and 3' bases. In particular poly(G) ends seemed to exert a complex qualitative and quantitative effect which could be up- or down-modulating depending on whether the ODN backbone was phosphorothioate modified or not.


Relationship between the resting heart rate and the extent of coronary artery disease as assessed by myocardial perfusion SPECT.
Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD. The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used. CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p <0.05 for all). Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself.


Characterization of early steps in the poliovirus infection process: receptor-decorated liposomes induce conversion of the virus to membrane-anchored entry-intermediate particles.
The mechanism by which poliovirus infects the cell has been characterized by a combination of biochemical and structural studies, leading to a working model for cell entry. Upon receptor binding at physiological temperature, native virus (160S) undergoes a conformational change to a 135S particle from which VP4 and the N terminus of VP1 are externalized. These components interact with the membrane and are proposed to form a membrane pore. An additional conformational change in the particle is accompanied by release of the infectious viral RNA genome from the particle and its delivery, presumably through the membrane pore into the cytoplasm, leaving behind an empty 80S particle. In this report, we describe the generation of a receptor-decorated liposome system, comprising nickel-chelating nitrilotriacetic acid (NTA) liposomes and His-tagged poliovirus receptor, and its use in characterizing the early events in poliovirus infection. Receptor-decorated liposomes were able to capture virus and induce a temperature-dependent virus conversion to the 135S particle. Upon conversion, 135S particles became tethered to the liposome independently of receptor by a membrane interaction with the N terminus of VP1. Converted particles had lost VP4, which partitioned with the membrane. The development of a simple model membrane system provides a novel tool for studying poliovirus entry. The liposome system bridges the gap between previous studies using either soluble receptor or whole cells and offers a flexible template which can be extrapolated to electron microscopy experiments that analyze the structural biology of nonenveloped virus entry.


Green tea, black tea consumption and risk of lung cancer: a meta-analysis.
Studies investigating the association of green tea and black tea consumption with lung cancer risk have reported inconsistent findings. To provide a quantitative assessment of this association, we conducted a meta-analysis on the topic. Studies were identified by a literature search in PubMed from 1966 to November 2008 and by searching the reference lists of relevant studies. Summary relative risk (RR) estimates and their corresponding 95% confidence intervals (CIs) were calculated based on random-effects model. Our meta-analysis included 22 studies provided data on consumption of green tea or black tea, or both related to lung cancer risk. For green tea, the summary RR indicated a borderline significant association between highest green tea consumption and reduced risk of lung cancer (RR=0.78, 95% CI=0.61-1.00). Furthermore, an increase in green tea consumption of two cups/day was associated with an 18% decreased risk of developing lung cancer (RR=0.82, 95% CI=0.71-0.96). For black tea, no statistically significant association was observe through the meta-analysis (highest versus non/lowest, RR=0.86, 95% CI=0.70-1.05; an increment of two cups/day, RR=0.82, 95% CI=0.65-1.03). In conclusion, our data suggest that high or an increase in consumption of green tea but not black tea may be related to the reduction of lung cancer risk.


Comparison of Drosophila melanogaster Embryo and Adult Proteome by SWATH-MS Reveals Differential Regulation of Protein Synthesis, Degradation Machinery, and Metabolism Modules.
An important area of modern biology consists of understanding the relationship between genotype and phenotype. However, to understand this relationship it is essential to investigate one of the principal links between them: the proteome. With the development of recent mass-spectrometry approaches, it is now possible to quantify entire proteomes and thus relate them to different phenotypes. Here, we present a comparison of the proteome of two extreme developmental states in the well-established model organism Drosophila melanogaster: adult and embryo. Protein modules such as ribosome, proteasome, tricarboxylic acid cycle, glycolysis, or oxidative phosphorylation were found differentially expressed between the two developmental stages. Analysis of post-translation modifications of the proteins identified in this study indicates that they generally follow the same trend as their corresponding protein. Comparison between changes in the proteome and the transcriptome highlighted patterns of post-transcriptional regulation for the subunits of protein complexes such as the ribosome and the proteasome, whereas protein from modules such as TCA cycle, glycolysis, and oxidative phosphorylation seem to be coregulated at the transcriptional level. Finally, the impact of the endosymbiont Wolbachia pipientis on the proteome of both developmental states was also investigated.


Optimized detection of sequence variation in heterozygous genomes using DNA microarrays with isothermal-melting probes.
The use of DNA microarrays to identify nucleotide variation is almost 20 years old. A variety of improvements in probe design and experimental conditions have brought this technology to the point that single-nucleotide differences can be efficiently detected in unmixed samples, although developing reliable methods for detection of mixed sequences (e.g., heterozygotes) remains challenging. Surprisingly, a comprehensive study of the probe design parameters and experimental conditions that optimize discrimination of single-nucleotide polymorphisms (SNPs) has yet to be reported, so the limits of this technology remain uncertain. By targeting 24,549 SNPs that differ between two Saccharomyces cerevisiae strains, we studied the effect of SNPs on hybridization efficiency to DNA microarray probes of different lengths under different hybridization conditions. We found that the critical parameter for optimization of sequence discrimination is the relationship between probe melting temperature (T(m)) and the temperature at which the hybridization reaction is performed. This relationship can be exploited through the design of microarrays containing probes of equal T(m) by varying the length of probes. We demonstrate using such a microarray that we detect >90% homozygous SNPs and >80% heterozygous SNPs using the SNPScanner algorithm. The optimized design and experimental parameters determined in this study should guide DNA microarray designs for applications that require sequence discrimination such as mutation detection, genotyping of unmixed and mixed samples, and allele-specific gene expression. Moreover, designing microarray probes with optimized sensitivity to mismatches should increase the accuracy of standard microarray applications such as copy-number variation detection and gene expression analysis.


Health services research related to performance indicators and benchmarking in Europe.
Measuring quality of care through performance indicators and subsequently using these to compare, learn, and improve (benchmarking) has become a central component of health care policy. This paper aims to identify the main themes of health services research in this area and focuses on opportunities for improving the evidence underpinning performance indicators. A literature survey was carried out to identify research activities and main research themes in Europe in the years 2000-09. Identified literature was categorized into sub-topics and for each topic the main methodological issues were identified and discussed. Experts validated the findings and explored the potential for related further European research. The distribution of research on performance and benchmarking across EU member states varies in time, scope and settings with a large amount of studies focusing on hospitals. Eight specific fields of research were identified (research on concepts and performance frameworks; performance indicators and benchmarking using mortality data; performance indicators and benchmarking related to cancer care; performance indicators and benchmarking on care delivered in hospitals; patient safety indicators; performance indicators in primary care; patient experience; research on the practice of benchmarking and performance improvement). Expert discussions confirmed that research on performance indicators and benchmarking should focus on the development of indicators, as well as their use. The research should involve the potential users and incorporate scientific approaches from biomedicine and epidemiology as well as the social sciences. Further progress is hampered by data availability. Issues which need to be addressed include the use of unique patient identifiers (UPIs) to facilitate linkages between separate databases; standardized measurement of the experiences of patients and others; and deepening collaboration between Eurostat, the World Health Organization (WHO), and the Organization for Economic Co-operation and Development (OECD) to facilitate the availability of internationally comparable performance information. This study suggests a number of themes for future research. These include testing and improving: the validity and reliability of performance indicators, especially related to avoidable mortality and other outcome indicators; the effectiveness and efficiency of embedding performance indicators in the various governance, monitoring and management models, and their effect on health systems, services and professionals; and the effectiveness and efficiency of linking performance indicators to other national and international strategies and policies such as accreditation and certification, practice guidelines, audits, quality systems, patient safety strategies, national standards on volume and/or quality, public reporting, pay-for-performance and patient/consumer involvement. The field would benefit from strengthening the clearinghouse function for research findings, training of researchers and appropriate scientific publication media. Results should be systematically shared with policy-makers and managers, and networking stimulated between the growing number of regional and national institutes involved in quality measurement and reporting.


Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia.
We tested the antiplatelet effects of low-dose aspirin in patients with occlusive cerebrovascular disease, because conventional dosage aspirin inhibits vascular synthesis of prostacyclin at the same time that it inhibits platelets. The effects on platelet function and thromboxane A2 synthesis of 40 mg of aspirin daily or 40 mg aspirin plus dipyridamole were measured in 23 patients starting within a week after the onset of cerebral ischemia. All patients had normal baseline platelet aggregation responses to four stimuli: arachidonate, epinephrine, adenosine diphosphate and collagen. The generation of thromboxane A2 by platelets, measured as serum thromboxane B2, was also normal. After 3 to 7 days of low dose aspirin therapy, platelet aggregation responses were suppressed to the extent observed with higher dosage aspirin. Serotonin release during platelet aggregation was inhibited by more than 95% and thromboxane B2 levels in clotted blood fell by more than 95%. Responses to aspirin treatment were similar in patients with transient ischemic attacks and in those with stroke and were also similar in both sexes. No differences in platelet responses were observed between patients receiving aspirin alone and aspirin plus dipyridamole. Thus 40 mg aspirin daily inhibited platelet responses as effectively as higher doses of aspirin in patients who had recent cerebral ischemia and showed a cumulative antiplatelet effect.


Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells.
This study aimed to investigate the role of fatty acid synthase (FASN) in the epithelial-mesenchymal transition (EMT) of breast cancer cells. MCF-7 cells and MCF-7 cells overexpressing mitogen-activated protein kinase 5 (MCF-7-MEK5) were used in this study. MCF-7-MEK5 cells showed stable EMT characterized by increased vimentin and decreased E-cadherin expression. An In vivo animal model was established using the orthotopic injection of MCF-7 or MCF-7-MEK5 cells. Real-time quantitative PCR and western blotting were used to detect the expression levels of FASN and its downstream proteins liver fatty acid-binding protein (L-FABP) and VEGF/VEGFR-2 in both in vitro and in vivo models (nude mouse tumor tissues). In MCF-7-MEK5 cells, significantly increased expression of FASN was associated with increased levels of L-FABP and VEGF/VEGFR-2. Cerulenin inhibited MCF-7-MEK5 cell migration and EMT, and reduced FASN expression and down-stream proteins L-FABP, VEGF, and VEGFR-2. MCF-7-MEK5 cells showed higher sensitivity to Cerulenin than MCF-7 cells. Immunofluorescence revealed an increase of co-localization of FASN with VEGF on the cell membrane and with L-FABP within MCF-7-MEK5 cells. Immunohistochemistry further showed that increased percentage of FASN-positive cells in the tumor tissue was associated with increased percentages of L-FABP- and VEGF-positive cells and the Cerulenin treatment could reverse the effect. Altogether, our results suggest that FASN is essential to EMT possibly through regulating L-FABP, VEGF and VEGFR-2. This study provides a theoretical basis and potential strategy for effective suppression of malignant cells with EMT.


Ultrafast inter-ionic charge transfer of transition-metal complexes mapped by femtosecond X-ray powder diffraction.
The transient electronic and molecular structure arising from photoinduced charge transfer in transition metal complexes is studied by X-ray powder diffraction with a 100 fs temporal and atomic spatial resolution. Crystals containing a dense array of Fe(II)-tris(bipyridine) ([Fe(bpy)3](2 +)) complexes and their [Formula: see text] counterions display pronounced changes of electron density that occur within the first 100 fs after two-photon excitation of a small fraction of the [Fe(bpy)3](2 +) complexes. Transient electron density maps derived from the diffraction data reveal a transfer of electronic charge from the Fe atoms and-so far unknown-from the [Formula: see text] counterions to the bipyridine units. Such charge transfer (CT) is connected with changes of the inter-ionic and the Fe-bipyridine distances. An analysis of the electron density maps demonstrates the many-body character of charge transfer which affects approximately 30 complexes around a directly photoexcited one. The many-body behavior is governed by the long-range Coulomb forces in the ionic crystals and described by the concept of electronic polarons.


Safety and feasibility of robotic-assisted Ivor-Lewis esophagectomy.
Esophagectomy is associated with substantial morbidity. Robotic surgery allows complex resections to be performed with potential benefits over conventional techniques. We applied this technology to transthoracic esophagectomy to assess safety, feasibility, and reliability of this technology. A retrospective cohort study of all patients undergoing robotic-assisted Ivor-Lewis esophagectomy (RAIL) from 2009 to 2014 was conducted. Clinicopathologic factors and surgical outcomes were recorded and compared. All statistical tests were two-sided and a P-value of <0.05 was considered statistically significant. We identified 147 patients with an average age 66 ± 10 years. Neoadjuvant therapy was administered to 114 (77.6%) patients, and all patients underwent a R0 resection. The mean operating room (OR) time was 415 ± 84.6 minutes with a median estimated blood loss (EBL) of 150 (25-600) mL. Mean intensive care unit (ICU) stay was 2.00 ± 4.5 days, median length of hospitalization (LOH) was 9 (4-38) days, and readmissions within 90 days were low at 8 (5.5%). OR time decreased from 471 minutes to 389 minutes after 20 cases and a further decrease to mean of 346 minutes was observed after 120 cases. Complications occurred in 37 patients (25.2%). There were 4 anastomotic (2.7%) leaks. Thirty and 90-day mortality was 0.68% and 1.4%, respectively. This represents to our knowledge the largest series of robotic esophagectomies. RAIL is a safe surgical technique that provides an alternative to standard minimally invasive and open techniques. In our series, there was no increased risk of LOH, complications, or death and re-admission rates were low despite earlier discharge.


Mercury and Mink. II. Experimental methyl mercury intoxication.
Adult female mink were fed rations containing 1.1, 1.8, 4.8, 8.3 and 15.0 ppm mercury as methyl mercury chloride over a 93 day period. Histopathological evidence of injury was present in all groups. Mink fed rations containing 1.8 to 15.0 ppm mercury developed clinical intoxication within the experimental period. The rapidity of onset of clinical intoxication was directly related to the mercury content of the ration. Mercury concentration in tissue of mink which died were similar, despite differences in mercury content of the diets and time of death. The average mercury concentration in the brain of mink which died was 11.9 ppm. The lesions of methyl mercury poisoning are described and criteria for diagnosis are discussed.


CRISPR-Cas guides the future of genetic engineering.
The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.


MedXN: an open source medication extraction and normalization tool for clinical text.
We developed the Medication Extraction and Normalization (MedXN) system to extract comprehensive medication information and normalize it to the most appropriate RxNorm concept unique identifier (RxCUI) as specifically as possible. Medication descriptions in clinical notes were decomposed into medication name and attributes, which were separately extracted using RxNorm dictionary lookup and regular expression. Then, each medication name and its attributes were combined together according to RxNorm convention to find the most appropriate RxNorm representation. To do this, we employed serialized hierarchical steps implemented in Apache's Unstructured Information Management Architecture. We also performed synonym expansion, removed false medications, and employed inference rules to improve the medication extraction and normalization performance. An evaluation on test data of 397 medication mentions showed F-measures of 0.975 for medication name and over 0.90 for most attributes. The RxCUI assignment produced F-measures of 0.932 for medication name and 0.864 for full medication information. Most false negative RxCUI assignments in full medication information are due to human assumption of missing attributes and medication names in the gold standard. The MedXN system (http://sourceforge.net/projects/ohnlp/files/MedXN/) was able to extract comprehensive medication information with high accuracy and demonstrated good normalization capability to RxCUI as long as explicit evidence existed. More sophisticated inference rules might result in further improvements to specific RxCUI assignments for incomplete medication descriptions.


Aeolian abrasion of rocks as a mechanism to produce methane in the Martian atmosphere.
Seasonal changes in methane background levels and methane spikes have been detected in situ a metre above the Martian surface, and larger methane plumes detected via ground-based remote sensing, however their origin have not yet been adequately explained. Proposed methane sources include the UV irradiation of meteoritic-derived organic matter, hydrothermal reactions with olivine, organic breakdown via meteoroid impact, release from gas hydrates, biological production, or the release of methane from fluid inclusions in basalt during aeolian erosion. Here we quantify for the first time the potential importance of aeolian abrasion as a mechanism for releasing trapped methane from within rocks, by coupling estimates of present day surface wind abrasion with the methane contents of a variety of Martian meteorites, analogue terrestrial basalts and analogue terrestrial sedimentary rocks. We demonstrate that the abrasion of basalt under present day Martian rates of aeolian erosion is highly unlikely to produce detectable changes in methane concentrations in the atmosphere. We further show that, although there is a greater potential for methane production from the aeolian abrasion of certain sedimentary rocks, to produce the magnitude of methane concentrations analysed by the Curiosity rover they would have to contain methane in similar concentrations as economic reserved of biogenic/thermogenic deposits on Earth. Therefore we suggest that aeolian abrasion is an unlikely origin of the methane detected in the Martian atmosphere, and that other methane sources are required.


The human T-cell receptor.
Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to the identification of the human T-cell antigen receptor as a surface complex comprised of a clonotypic 90-kD Ti heterodimer and the invariant 20- and 25-kD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. Moreover, the presence of unique peptides following proteolysis of different Ti molecules isolated by non-cross-reactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and the beta subunits. N-Terminal amino acid sequencing and molecular cloning of the Ti beta subunit further show that it bears an homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Triggering of the T3-Ti receptor complex gives rise to specific antigen-induced proliferation through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors. The implications of these findings for understanding human T-cell growth and its regulation in disease states are discussed.