Viral phylodynamics.
Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viralphylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread[2], spatio-temporal dynamics including metapopulation dynamics[3], zoonotic transmission, tissue tropism[4], and antigenic drift[5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics.


The tumor accumulation and therapeutic efficacy of doxorubicin carried in calcium phosphate-reinforced polymer nanoparticles.
A mineral (calcium phosphate, CaP)-reinforced core-shell-corona micelle was evaluated as a nanocarrier of doxorubicin (DOX) for cancer therapy. The polymer micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L-phenylalanine) (PEG-PAsp-PPhe) in the aqueous phase provided the three distinct functional domains: the hydrated PEG outer corona for prolonged circulation, the anionic PAsp middle shell for CaP mineralization, and the hydrophobic PPhe inner core for DOX loading. CaP mineralization was performed by initial electrostatic localization of calcium ions at anionic PAsp shells, and the consequent addition of phosphate anions to trigger the growth of CaP. The mineralization did not affect the micelle size or the spherical morphology. The CaP-mineralized micelles exhibited enhanced serum stability. The DOX release from the DOX-loaded mineralized micelles (DOX-CaP-PM) at physiological pH was efficiently inhibited, whereas at an endosomal pH (pH 4.5), DOX release was facilitated due to the rapid dissolution of the CaP mineral layers in the middle shell domains. The in vivo tissue distribution and tumor accumulation of the DOX-CaP-PM that were labeled with a near-infrared fluorescent (NIRF) dye, Cy5.5, were monitored in MDA-MB231 tumor-bearing mice. Non-invasive real-time optical imaging results indicated that the DOX-CaP-PM exhibited enhanced tumor specificity due to the prolonged stable circulation in the blood and an enhanced permeation and retention (EPR) effect compared with the DOX-loaded nonmineralized polymer micelles (DOX-NPM). The DOX-CaP-PM exhibited enhanced therapeutic efficacy in tumor-bearing mice compared with free DOX and DOX-NPM. The CaP mineralization on assembled nanoparticles may serve as a useful guide for enhancing the antitumor therapeutic efficacy of various polymer micelles and nano-aggregates.


Ultrathin β-tellurium layers grown on highly oriented pyrolytic graphite by molecular-beam epitaxy.
Monolayer tellurium (Te) or tellurene has been suggested by a recent theory as a new two-dimensional (2D) system with great electronic and optoelectronic promises. Here we present an experimental study of epitaxial Te deposited on highly oriented pyrolytic graphite (HOPG) by molecular-beam epitaxy. Scanning tunneling microscopy of ultrathin layers of Te reveals rectangular surface cells with the cell size consistent with the theoretically predicted β-tellurene, whereas for thicker films, the cell size is more consistent with that of the [101[combining macron]0] surface of the bulk Te crystal. Scanning tunneling spectroscopy measurements show that the films are semiconductors with the energy band gaps decreasing with increasing film thickness, and the gap narrowing occurs predominantly at the valence-band maximum (VBM). The latter is understood by strong coupling of states at the VBM but a weak coupling at conduction band minimum (CBM) as revealed by density functional theory calculations.


Clinical examination findings as prognostic factors in low back pain: a systematic review of the literature.
There is a strong tradition of performing a clinical examination of low back pain (LBP) patients and this is generally recommended in guidelines. However, establishing a pathoanatomic diagnosis does not seem possible in most LBP patients and clinical tests may potentially be more relevant as prognostic factors. The aim of this review of the literature was to systematically assess the association between low-tech clinical tests commonly used in adult patients with acute, recurrent or chronic LBP and short- and long-term outcome. MEDLINE, Embase, and MANTIS were searched from inception to June 2012. Prospective clinical studies of adult patients with LBP with or without leg pain and/or signs of nerve root involvement or spinal stenosis, receiving non-surgical or no treatment, which investigated the association between low-tech clinical tests and outcome were included. Study selection, data extraction and appraisal of study quality were performed independently by two reviewers. A total of 5,332 citations were retrieved and screened for eligibility, 342 articles were assessed as full text and 49 met the inclusion criteria. Due to clinical and statistical heterogeneity, qualitative synthesis rather than meta-analysis was performed. Associations between clinical tests and outcomes were often inconsistent between studies. In more than one third of the tests, there was no evidence of the tests being associated with outcome. Only two clinical tests demonstrated a consistent association with at least one of the outcomes: centralization and non-organic signs. For most clinical tests in LBP there is not consistent evidence for an association with outcome. Centralization and non-organic signs are exceptions from that. None of the other clinical tests have been investigated in confirmatory studies and study quality is generally low. There is a need for hypothesis testing studies designed specifically to investigate the prognostic value of the clinical tests, and a need for standardization of the performance and interpretation of tests.


Solute crystallization in frozen systems-use of synchrotron radiation to improve sensitivity.
To demonstrate the sensitivity of low temperature synchrotron X-ray diffractometry (SXRD) for detecting solute crystallization in frozen sodium phosphate buffer solutions. To determine the effect of annealing on solute crystallization in frozen solutions. Sodium phosphate buffer solutions, at initial buffer concentrations ranging from 1 to 100 mM (pH 7.4) were cooled to -50 degrees C. The crystallization of disodium hydrogen phosphate dodecahydrate (Na(2)HPO(4) *12H(2)O) was monitored using a laboratory as well as a synchrotron source. At selected concentrations, the effect of annealing (at -20 degrees C) was investigated. With the laboratory source, solute crystallization, based on the appearance of one diagnostic peak with a d-spacing of 5.4 A, was evident only when the initial buffer concentration was at least 50 mM. In contrast, using SXRD, crystallization was detected at initial buffer concentrations down to 1 mM. In addition, the use of a high-resolution 2D detector enabled the visualization of numerous diffraction rings of the crystalline solute. At both 10 and 100 mM buffer concentration, there was no increase in solute crystallization due to annealing. By using synchrotron radiation, solute crystallization was detected with substantially increased sensitivity, making the technique useful for freeze-drying cycles of practical and commercial importance. Since numerous peaks of the crystalline solute appeared, the technique has potential utility in complex, multi-component systems.


Groundwater-driven nutrient inputs to coastal lagoons: The relevance of lagoon water recirculation as a conveyor of dissolved nutrients.
Evaluating the sources of nutrient inputs to coastal lagoons is required to understand the functioning of these ecosystems and their vulnerability to eutrophication. Whereas terrestrial groundwater processes are increasingly recognized as relevant sources of nutrients to coastal lagoons, there are still limited studies evaluating separately nutrient fluxes driven by terrestrial groundwater discharge and lagoon water recirculation through sediments. In this study, we assess the relative significance of these sources in conveying dissolved inorganic nutrients (NO3-, NH4+ and PO43-) to a coastal lagoon (La Palme lagoon; France, Mediterranean Sea) using concurrent water and radon mass balances. The recirculation of lagoon water through sediments represents a source of NH4+ (1900-5500 mol d-1) and PO43- (22-71 mol d-1), but acts as a sink of NO3-. Estimated karstic groundwater-driven inputs of NO3-, NH4+ and PO43- to the lagoon are on the order of 200-1200, 1-12 and 1.5-8.7 mol d-1, respectively. A comparison between the main nutrient sources to the lagoon (karstic groundwater, recirculation, diffusion from sediments, inputs from a sewage treatment plant and atmospheric deposition) reveals that the recirculation of lagoon water through sediments is the main source of both dissolved inorganic nitrogen (DIN) and phosphorous (DIP) to La Palme lagoon. These results are in contrast with several studies conducted in systems influenced by terrestrial groundwater inputs, where groundwater is often assumed to be the main pathway for dissolved inorganic nutrient loads. This work highlights the important role of lagoon water recirculation through permeable sediments as a major conveyor of dissolved nutrients to coastal lagoons and, thus, the need for a sound understanding of the recirculation-driven nutrient fluxes and their ecological implications to sustainably manage lagoonal ecosystems.


Ability of obstacle crossing is not associated with falls in independent ambulatory patients with spinal cord injury.
A 6-month prospective design. To investigate the relationship between ability of obstacle crossing and falls in independent ambulatory participants with spinal cord injury (SCI). A tertiary rehabilitation center. Ninety-four participants were evaluated for their SCI characteristics, ability of walking over small obstacles and functional ability relating to dynamic balance control, lower-extremity motor strength (LEMS) and walking ability. Their fall data were then prospectively monitored every month for 6 months. Twenty-four participants failed in obstacle crossing. However, only eight of the thirty-three participants who fell during the follow-up period were unable to clear the obstacle while walking. The LEMS and functional ability of the participants who failed were significantly poorer than those of individuals who passed an obstacle-crossing test (P⩽0.001). For the falls, significant differences between the groups were found only in age and tactile scores. The findings further indicated that failures on obstacle crossing were not significantly associated with falls (P>0.05). Ability of obstacle crossing in a closed/controlled environment clearly correlated with intrinsic causes, whereas a fall in an open environment may be associated with not only intrinsic but also extrinsic causes. Therefore, apart from functional ability, rehabilitation professionals may need to consider extrinsic factors around falls in order to manage risk of injury to the patients.


Risk factors for complications associated with upper gastrointestinal foreign bodies.
To investigate predictive risk factors associated with complications in the endoscopic removal of foreign bodies from the upper gastrointestinal tract. We retrospectively reviewed the medical records of 194 patients with a diagnosis of foreign body impaction in the upper gastrointestinal tract, confirmed by endoscopy, at two university hospital in South Korea. Patient demographic data, including age, gender, intention to ingestion, symptoms at admission, and comorbidities, were collected. Clinical features of the foreign bodies, such as type, size, sharpness of edges, number, and location, were analyzed. Endoscopic data those were analyzed included duration of foreign body impaction, duration of endoscopic performance, endoscopic device, days of hospitalization, complication rate, 30-d mortality rate, and the number of operations related to foreign body removal. The types of upper gastrointestinal foreign bodies included fish bones, drugs, shells, meat, metal, and animal bones. The locations of impacted foreign bodies were the upper esophagus (57.2%), mid esophagus (28.4%), stomach (10.8%), and lower esophagus (3.6%). The median size of the foreign bodies was 26.2 ± 16.7 mm. Among 194 patients, endoscopic removal was achieved in 189, and complications developed in 51 patients (26.9%). Significant complications associated with foreign body impaction and removal included deep lacerations with minor bleeding (n = 31, 16%), ulcer (n = 11, 5.7%), perforation (n = 3, 1.5%), and abscess (n = 1, 0.5%). Four patients underwent operations because of incomplete endoscopic foreign body extraction. In multivariate analyses, risk factors for endoscopic complications and failure were sharpness (HR = 2.48, 95%CI: 1.07-5.72; P = 0.034) and a greater than 12-h duration of impaction (HR = 2.42, 95%CI: 1.12-5.25, P = 0.025). In cases of longer than 12 h since foreign body ingestion or sharp-pointed objects, rapid endoscopic intervention should be provided in patients with ingested foreign bodies.


Coherent optical correlator based on combined halftone and position modulation of light phase.
Usually only a halftone (grayscale) modulation of light is used to present the processed and reference signals in the input plane of analog coherent optical (ACO) correlators, based on spatially integrating the product of two (processed and reference) signals. The halftone modulation requires two transparencies to record two signals separately, as the desired product of two spatial signals is obtained by sequential location of two spatial halftone records along the light path. Such an optical layout leads to the need for precision mutual alignment of two separate signal recordings. This paper presents a one-stage ACO correlation method based on combined halftone and position modulation of the light phase, which is produced by joint phase recording two signals on a single transparency. The joint phase recording provides the high optical efficiency of informational light modulation, automatically supports the spatial coincidence of corresponding elements of both recorded signals, and provides the same spatial scale for both recordings. The suggested method can also be used for introducing phase weight functions in the schemes of space-time ACO processing of wave signals. Advantages of ACO signal processing methods in comparison with corresponding electronic approaches are briefly noted.


Women's property rights and gendered policies: implications for women's long-term welfare in rural Tanzania.
This paper evaluates effects of community-level women's property and inheritance rights on women's economic outcomes using a 13 year longitudinal panel from rural Tanzania. In the preferred model specification, inverse probability weighting is applied to a woman-level fixed effects model to control for individual-level time invariant heterogeneity and attrition. Results indicate that changes in women's property and inheritance rights are significantly associated with women's employment outside the home, self-employment and earnings. Results are not limited to sub-groups of marginalised women. Findings indicate lack of gender equity in sub-Saharan Africa may inhibit economic development for women and society as a whole.


The politics of avoidable blindness in Latin America--surgery, solidarity, and solutions: the case of Misión Milagro.
Avoidable blindness, especially when caused by cataracts, is a disease primarily of the economically disadvantaged sectors of the population. With a focus on Latin America and the Caribbean, this paper focuses on the program Misión Milagro within its historical, political, and economic contexts. This initiative, led by the governments of Cuba and Venezuela, covers close to 35 countries across Latin America, the Caribbean, Asia, and Africa. It is well-known throughout Latin America as close to 2 million patients have undergone free screening, corrective surgery, and rehabilitation since its inception in 2004. Misión Milagro shows that implementation of a massive initiative to curb avoidable blindness caused by cataracts in a relatively short time is feasible. The program is also built upon a unique model of international cooperation, which stresses social objectives and solidarity rather than hegemonic international initiatives built on commercial relationships. It also provides elements that could be applied to other public health issues of global or national relevance, not only to other low-middle-income countries, but also to high-income countries such as Canada.


Reading heredity in racist environments: epigenetic imaginaries in Bessie Head's The Cardinals.
The field of epigenetics research shows us how we are constructed by what is without-materially, socially and environmentally-while also taking us beyond narrow genetic determinants of heredity. If misappropriated, epigenetics research risks pathologising particular social or ethnic groups as biologically damaged. However, epigenetics may also allow us to better conceptualise the biopsychosocially constitutive nature of racist environments. In this article, I argue that epigenetic understandings of embodiment allow us to follow Achille Mbembe's recommendation: that to account for postcolonial relations of power-their effectiveness and psychology-we need to go beyond the binary categories (like passivity vs resistance) so frequently deployed in the analysis of domination. To demonstrate this, I offer a literary example from apartheid South Africa. In Bessie Head's The Cardinals, embodiment is imagined as the hereditary effect of segregated environmental space. The Cardinals thus offers something like a literary imagining of the epigenetic (as a material change that is heritable), before contemporary advances in epigenetics research made the connection between environment and embodiment more sensible in molecular terms. Head radically calls into question the certainty of biological identity: characters are 'marked' deterministically by their environments but ultimately the mutability of such 'epigenetic' markers is revealed when the individual transcends apartheid's spatial and racial demarcations. Writing in the context of apartheid, Head's engagement with non-genetic understandings of identity is a motivated attempt to evade the stigmatising categories and 'genetic' assumptions of scientific racism, which constructed races as biologically distinct (modern genetic science shows us that there is no genetic basis for 'race'). Instead, Head positions environmental spaces, including the Indian Ocean (a conduit for South Asian arrivals and for new philosophies and the potential political affiliations that arrive with them) as points of genealogical origin and as constitutive of identity in non-deterministic ways.


Isolating the role of time in bed restriction in the treatment of insomnia: a randomized, controlled, dismantling trial comparing sleep restriction therapy with time in bed regularization.
Sleep restriction therapy (SRT) is one of the most effective treatments for insomnia. Restriction of time in bed (TIB) is assumed to be the central mechanism through which SRT improves sleep consolidation and reduces insomnia symptoms. This hypothesis has never been directly tested. We designed a randomized, controlled, dismantling trial in order to isolate the role of TIB restriction in driving both clinical and polysomnographic sleep outcomes. Participants aged 25-55 who met diagnostic criteria for insomnia disorder were block-randomized (1:1) to 4 weeks of SRT or time in bed regularization (TBR), a treatment that involves the prescription of a regular but not reduced TIB. The primary outcome was assessed with the insomnia severity index (ISI) at baseline, 4-, and 12-weeks post-randomization. Secondary outcomes included sleep continuity (assessed via polysomnography, actigraphy, and diary) and quality of life. We performed intention-to-treat analyses using linear mixed models. Fifty-six participants (39 females, mean age = 40.78 ± 9.08) were assigned to SRT (n = 27) or TBR (n = 29). Daily monitoring of sleep via diaries and actigraphy confirmed large group differences in TIB (d range = 1.63-1.98). At 4-weeks post-randomization, the adjusted mean difference for the ISI was -4.49 (d = -1.40) and -4.35 at 12 weeks (d = -1.36), indicating that the SRT group reported reduced insomnia severity relative to TBR. Robust treatment effects in favor of SRT were also found for objective and self-reported sleep continuity variables (d range = 0.40-0.92) and sleep-related quality of life (d = 1.29). For the first time, we demonstrate that TIB restriction is superior to the regularization of TIB on its own. Our results underscore the centrality of the restriction component in reducing insomnia symptoms and consolidating sleep.


New beta-alanine derivatives are orally available glucagon receptor antagonists.
A weak human glucagon receptor antagonist with an IC50 of 7 microM was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.


The developmental regulation of the human zeta-globin gene in transgenic mice employing beta-galactosidase as a reporter gene.
We have investigated the developmental and tissue specific expression of the human embryonic zeta-globin gene in transgenic mice. A construct containing 550 bp of zeta-globin 5' flanking region, fused to a beta-galactosidase (lacZ) reporter gene and linked to the locus control region (LCR)-like alpha positive regulatory element (alpha PRE) was employed for the production of transgenic mice. Firstly, we compared the number of live born transgenic mice containing this construct to the number of live born transgenic mice containing the entire zeta-globin gene linked to the alpha PRE or the beta LCR. Data showed that 12% of mice generated from eggs injected with zeta-promoter/lacZ/alpha PRE DNA were transgenic compared to only 2% of mice generated from eggs injected with the entire zeta-globin gene linked to the alpha PRE or the beta LCR. The reduced number of live born transgenic mice containing the latter constructs suggests that death of transgenic embryos, possibly due to thalassaemia, may be occurring. X-gal staining of whole embryos containing the lacZ gene revealed that zeta-globin promoter activity was most pronounced at 8.5-9.5 days of development and was restricted to erythroid cells. By 15 days of development, no zeta-globin promoter activity was detected. These results suggest that the alpha PRE can direct high level expression from the zeta-globin promoter and that sequences required for the correct tissue and developmental specific expression of the human zeta-globin gene are present within 550 bp's of 5' flanking region. Sequences within the body of the zeta-globin gene or 3' of the cap site do not appear to be necessary for correct zeta-globin developmental regulation.


Historical determinants of contemporary attributes of African descendants in the Americas: the androgen receptor holds the key.
It is hypothesised that seemingly disparate and unrelated phenomena clustering in persons of African descent living in the Americas such as outstanding sprinting ability and high prostate cancer incidence and mortality are in fact related and emerge from enhanced testosterone responsiveness in descendants of African slaves surviving the transatlantic trade in Africans. It is postulated that the ability to have survived the middle passage was positively correlated with greater responsiveness of the androgen receptor to its primary ligands dihydrotestosterone and testosterone, and that slaves possessing more responsive androgen receptors experienced a survival advantage engendered by the enhanced anabolic effects which accrued such as increased red cell mass and therefore greater oxygen carrying capacity and tissue oxygen delivery enabling these slaves to tolerate stifling conditions in the hull of the slave ship, increased lean muscle mass and therefore greater surface area to volume ratio resulting in easier ability to dissipate heat and remain cool, and increased skin thickness and sebum production resisting the macerating effect of lying in admixed bodily fluids below deck. These androgen effects as well as others would have produced a survival advantage under the severe selection pressure created by the inhumane and physiologically challenging circumstances under which the slaves were transported from the interior of the African continent and West Africa to the 'New World'. This would result in a population shift favouring increased androgen receptor responsiveness in descendants of African slaves populating the Americas and a corresponding geographic and racial distribution of androgen related phenomena such as sprinting prowess and prostate cancer. African-Americans having the highest prostate cancer incidence rate and the Caribbean having the highest prostate cancer mortality rates in the world are consistent with this hypothesis as is the observation that the 10 fastest men and 9 fastest women of all time are exclusively the descendants of West African slaves who survived the middle passage. It is predicted that as yet undiscovered as well as known biological correlates of enhanced androgen receptor responsiveness such as relatively short CAG-repeats in the poly Q tail of exon 1 of the androgen receptor gene will be more prevalent among African-Americans and Afro-Caribbean peoples than among West Africans. It is also predicted that African-Americans and Afro-Caribbean peoples will have relatively shorter CAG-repeats in the androgen receptor gene compared to West Africans.


Rapid sampling of stochastic displacements in Brownian dynamics simulations.
We present a new method for sampling stochastic displacements in Brownian Dynamics (BD) simulations of colloidal scale particles. The method relies on a new formulation for Ewald summation of the Rotne-Prager-Yamakawa (RPY) tensor, which guarantees that the real-space and wave-space contributions to the tensor are independently symmetric and positive-definite for all possible particle configurations. Brownian displacements are drawn from a superposition of two independent samples: a wave-space (far-field or long-ranged) contribution, computed using techniques from fluctuating hydrodynamics and non-uniform fast Fourier transforms; and a real-space (near-field or short-ranged) correction, computed using a Krylov subspace method. The combined computational complexity of drawing these two independent samples scales linearly with the number of particles. The proposed method circumvents the super-linear scaling exhibited by all known iterative sampling methods applied directly to the RPY tensor that results from the power law growth of the condition number of tensor with the number of particles. For geometrically dense microstructures (fractal dimension equal three), the performance is independent of volume fraction, while for tenuous microstructures (fractal dimension less than three), such as gels and polymer solutions, the performance improves with decreasing volume fraction. This is in stark contrast with other related linear-scaling methods such as the force coupling method and the fluctuating immersed boundary method, for which performance degrades with decreasing volume fraction. Calculations for hard sphere dispersions and colloidal gels are illustrated and used to explore the role of microstructure on performance of the algorithm. In practice, the logarithmic part of the predicted scaling is not observed and the algorithm scales linearly for up to 4×106 particles, obtaining speed ups of over an order of magnitude over existing iterative methods, and making the cost of computing Brownian displacements comparable to the cost of computing deterministic displacements in BD simulations. A high-performance implementation employing non-uniform fast Fourier transforms implemented on graphics processing units and integrated with the software package HOOMD-blue is used for benchmarking.


Does maternal control during feeding moderate early infant weight gain?
Our objective with this study was to examine whether observed maternal control during feeding at 6 months of age moderates the development of early infant weight gain during the first year of life. Sixty-nine women were observed feeding their 6-month-old infants during a standard meal. Mealtimes were coded for maternal use of controlling feeding behavior. All infants were weighed at birth and at 6 and 12 months of age, and weight gain was calculated from birth to 6 months and from 6 to 12 months. Weight scores and weight gain scores were standardized for prematurity, age, and gender. Infant weight gain between 6 and 12 months of age was predicted by an interaction between early infant weight gain (birth to 6 months) and observed maternal control during feeding at 6 months. When maternal control was moderate or low, there was a significant interaction with weight gain from birth to 6 months in the prediction of later infant weight gain from 6 to 12 months, such that infants who showed slow early weight gain accelerated in their subsequent weight gain, and those with greater early weight gain decelerated. Conversely, when maternal control was high, infant weight gain followed the opposite pattern. Maternal control of solid feeding can moderate infant weight gain.


Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development.
Resistant mouse strains mount a protective T cell-mediated immune response upon infection with Leishmania (L.) parasites. Healing correlates with a T helper (Th) cell-type 1 response characterized by a pronounced IFN-γ production, while susceptibility is associated with an IL-4-dependent Th2-type response. It has been shown that dermal dendritic cells are crucial for inducing protective Th1-mediated immunity. Additionally, there is growing evidence that C-type lectin receptor (CLR)-mediated signaling is involved in directing adaptive immunity against pathogens. However, little is known about the function of the CLR Dectin-1 in modulating Th1- or Th2-type immune responses by DC subsets in leishmaniasis. We characterized the expression of Dectin-1 on CD11c+ DCs in peripheral blood, at the site of infection, and skin-draining lymph nodes of L. major-infected C57BL/6 and BALB/c mice and in peripheral blood of patients suffering from cutaneous leishmaniasis (CL). Both mouse strains responded with an expansion of Dectin-1+ DCs within the analyzed tissues. In accordance with the experimental model, Dectin-1+ DCs expanded as well in the peripheral blood of CL patients. To study the role of Dectin-1+ DCs in adaptive immunity against L. major, we analyzed the T cell stimulating potential of bone marrow-derived dendritic cells (BMDCs) in the presence of the Dectin-1 agonist Curdlan. These experiments revealed that Curdlan induces the maturation of BMDCs and the expansion of Leishmania-specific CD4+ T cells. Based on these findings, we evaluated the impact of Curdlan/Dectin-1 interactions in experimental leishmaniasis and were able to demonstrate that the presence of Curdlan at the site of infection modulates the course of disease in BALB/c mice: wild-type BALB/c mice treated intradermally with Curdlan developed a protective immune response against L. major whereas Dectin-1-/- BALB/c mice still developed the fatal course of disease after Curdlan treatment. Furthermore, the vaccination of BALB/c mice with a combination of soluble L. major antigens and Curdlan was able to provide a partial protection from severe leishmaniasis. These findings indicate that the ligation of Dectin-1 on DCs acts as an important checkpoint in adaptive immunity against L. major and should therefore be considered in future whole-organism vaccination strategies.


Physical health inequalities among gay and bisexual men in England: a large community-based cross-sectional survey.
Gay and bisexual men experience a disproportionate burden of ill health compared with the general male population. However, little is known regarding health inequalities that exist within this group. We describe five key physical health indicators and their variation across common axes of inequality. Community-based opportunistic sampling recruited 5799 gay and bisexual men to a self-completion Internet survey. Respondents provided data relating to their height, weight, physical activity and substance use (tobacco, alcohol, illicit drugs). Responses were compared across seven demographic characteristics. Indicators of problematic health behaviour were concentrated within different groups and inequalities were rarely observed in the same direction. Older men were more likely to be overweight and drink alcohol frequently but less likely to smoke or use illicit drugs. Men of Asian ethnicity were more likely to exercise infrequently but less likely to smoke. Men living in London were more likely to smoke and use illicit drugs but less likely to be overweight. However, lower education was associated with being overweight, frequent alcohol, low exercise and smoking. There is evidence of significant demographic variation in physical health-related behaviours among gay and bisexual men, and men with lower levels of education are consistently in greater need.


Effects of Tear Film Instability on Sensory Responses to Corneal Cold, Mechanical, and Chemical Stimuli.
To investigate the effects of tear film instability (TFI) induced by sustained tear exposure (STARE) on sensory responses to corneal cold, mechanical, and chemical stimuli. Fifteen normal subjects were enrolled. TFI was induced during 10 repeated trials of STARE. Pneumatic cold, mechanical, and chemical stimuli were delivered using a computer-controlled Belmonte esthesiometer on three separate visits. The magnitude of the sensory responses to threshold and suprathreshold (1.25 and 1.50 times threshold levels) stimuli were assessed for intensity, coolness or warmness, irritation and pain, using a 0 (none) to 100 (very strong) scale, before and after STARE trials. Symptoms of ocular discomfort were evaluated using the Current Symptom Questionnaire (CSQ). Repeated measures ANOVA was used for data analysis. Following STARE trials, the intensity and coolness ratings to cooling stimuli decreased (P = 0.043 and 0.044 for intensity and coolness, respectively), while rated irritation to mechanical stimuli was increased (P = 0.024). The CSQ scores also increased regardless of visits (all P < 0.001). Intensity ratings, coolness to room temperature stimuli and irritation to mechanical and chemical stimuli increased for all suprathreshold stimuli with increasing stimulus levels (P ≤ 0.005). Repeated TFI induced by STARE affects neurosensory function of the ocular surface. The decrease in reports of cooling and increase in irritation after repeated TFI suggest a complex interaction of neural mechanisms (particularly nonnociceptive cold and nociceptive mechanical) giving rise to ocular surface sensation in humans.


Effectiveness of upper versus lower cervical adjustments with respect to the amelioration of passive rotational versus lateral-flexion end-range asymmetries in otherwise asymptomatic subjects.
The effects of cervical spinal adjustments delivered bilaterally either to the upper cervical region (C2-C3) or to the lower cervical region (C6-C7), were compared in groups of asymptomatic subjects exhibiting goniometrically verified left-right rotational or left-right lateral-flexion passive end-range asymmetries of greater than 10 degrees. Goniometric evaluation both prior to, and again within 30 min following treatments revealed that lower cervical adjustments were far more effective for the amelioration of lateral-flexion asymmetries than were upper cervical ones, whereas upper cervical adjustments were found to be more effective for the amelioration of rotational asymmetries than those delivered to the lower cervical region. These results are consistent with the view that passive movement restriction exhibited along the rotational axis is attributable to factors related primarily to the upper cervical region, whereas restrictions of passive movement along the lateral axis are more attributable to factors related to the lower cervical region. Further support for the regional independence of these axis-specific relationships is provided by similar results obtained in groups of subjects who happened to exhibit both rotational as well as lateral-flexion asymmetries of greater than 10 degrees on the day of the experiment.


Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500).
To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R²=0.404). Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors.


Interstitial telomeric sequences (ITSs) are not located at the exact evolutionary breakpoints in primates.
Although their function has not yet been clearly elucidated, interstitial telomeric sequences (ITSs) have been cytogenetically associated with chromosomal reorganizations, fragile sites, and recombination hotspots. In this paper, we show that ITSs are not located at the exact evolutionary breakpoints of the inversions between human and chimpanzee and between human and rhesus macaque chromosomes. We proved that ITSs are not signs of repair in the breakpoints of the chromosome reorganizations analyzed. We found ITSs in the region (0.7-2.7 Mb) flanking one of the two breakpoints in all the inversions assessed. The presence of ITSs in those locations is not by chance. They are short (up to 7.83 repeats) and almost perfect (82.5-97.1% matches). The ITSs are conserved in the species compared, showing that they were present before the reorganizations occurred.


A meta-analysis on the impact of psychiatric disorders and maltreatment on cognition.
Few studies have attempted to describe the range of cognitive impairments in individuals with psychiatric disorders who experienced maltreatment as children. The aims of this meta-analysis were to establish the impact of maltreatment and psychiatric disorders on cognition, and to examine the change in impact from childhood to adulthood. Twelve publications from 1970 to 2013 were included, with the following inclusion criteria: (a) individuals with a psychiatric disorder who experienced maltreatment, (b) use of at least 1 standardized neuropsychological measure, and (c) use of a control group without any psychiatric disorder or mistreatment. The majority of studies (10/12) were about posttraumatic stress disorder. Several effect sizes were calculated (Hedge's g) according to the cognitive domains. The results of the meta-analysis demonstrate that the combination of psychiatric disorders and childhood maltreatment has a negative impact on global cognitive performance, with a moderate effect size (g = -0.59). The most affected cognitive domains for individuals aged 7- to 18-years-old were visual episodic memory (g = -0.97), executive functioning (g = -0.90), and intelligence (g = -0.68). For individuals over the age of 18-years-old, the most affected cognitive domains were verbal episodic memory (g = -0.77), visuospatial/problem solving (g = -0.73), and attention (g = -0.72). The impact of maltreatment and psychiatric disorders was greater in children than in adults (slope = 0.008, p < .002). The results suggest that exposure to maltreatment and the presence of psychiatric disorders have a broad impact on cognition, with specific neuropsychological profile.


Flagella and curli fimbriae are important for the growth of Salmonella enterica serovars in hen eggs.
Salmonella enterica serovar Enteritidis is unable to multiply in the albumen of fresh eggs and must gain access to the yolk contents in order to multiply to a high level (>10(6) c.f.u. per ml egg contents). As human Salmonella infections resulting from the consumption of infected eggs more frequently involve serovar Enteritidis phage type (PT) 4 than other serovars or PTs, a number of isolates of various S. enterica serovars were examined for their ability to multiply to a high level in eggs over a period of 8 days storage at 20 degrees C. Their behaviour was compared to that of a range of defined fimbrial and flagella mutants of S. Enteritidis. Strains that did not express flagella were unable to multiply in eggs, and those deficient for curli fimbriae, including strains of S. Enteritidis PT6, displayed high-level growth in significantly fewer eggs than those able to express curli. Most S. Enteritidis strains multiplied to a high level in between 5 and 10 % of eggs during 8 days storage. One PT4 strain, though, showed high levels of growth in more than 25 % of eggs over this period, significantly higher than the other PTs or the two other isolates of PT4 tested. This ability may be important for the association of PT4 infection with the consumption of eggs.


The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion.
Viperin (also known as radical SAM domain-containing 2 (RSAD2)) is an interferon-inducible and evolutionary conserved protein that participates in the cell's innate immune response against a number of viruses. Viperin mRNA is a substrate for endoribonucleolytic cleavage by RNase mitochondrial RNA processing (MRP) and mutations in the RNase MRP small nucleolar RNA (snoRNA) subunit of the RNase MRP complex cause cartilage-hair hypoplasia (CHH), a human developmental condition characterized by metaphyseal chondrodysplasia and severe dwarfism. It is unknown how CHH-pathogenic mutations in RNase MRP snoRNA interfere with skeletal development, and aberrant processing of RNase MRP substrate RNAs is thought to be involved. We hypothesized that viperin plays a role in chondrogenic differentiation. Using immunohistochemistry, real-time quantitative PCR, immunoblotting, ELISA, siRNA-mediated gene silencing, plasmid-mediated gene overexpression, label-free MS proteomics, and promoter reporter bioluminescence assays, we discovered here that viperin is expressed in differentiating chondrocytic cells and regulates their protein secretion and the outcome of chondrogenic differentiation by influencing transforming growth factor β (TGF-β)/SMAD family 2/3 (SMAD2/3) activity via C-X-C motif chemokine ligand 10 (CXCL10). Of note, we observed disturbances in this viperin-CXCL10-TGF-β/SMAD2/3 axis in CHH chondrocytic cells. Our results indicate that the antiviral protein viperin controls chondrogenic differentiation by influencing secretion of soluble proteins and identify a molecular route that may explain impaired chondrogenic differentiation of cells from individuals with CHH.


Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis.
Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.


Decision Matrix-Guided Treatment of Infected Hip Resurfacing.
Infection can nullify the benefits of a successful hip resurfacing arthroplasty (HRA). Even with infection, it may be feasible to meet a patient's desire to retain the implant. The author reviewed records of 301 patients with infected hip resurfacing. Patients expressed their treatment preference using a decision matrix that considered treatment efficacy, consequences of treatment failure, probability of infection worsening, and treatment side effects. Patient interviews were analyzed to determine their experience with treatment. Treatment alternatives were (1) no surgery, oral antibiotics, and local incision care; (2) surgical debridement, IV antibiotics, and implant retention; (3) one-stage explantation, IV antibiotics, and reimplantation generally with conversion to total hip replacement; and (4) two-stage reimplantation with conversion to total hip replacement. Mean follow-up was 9 years (range, 2-34). Pretreatment qualitative themes found that some patients believed their early infection symptoms were not validated, leading to diagnostic delays. During treatment, themes centered on mobility and lifestyle limitations for those receiving revision surgery. Posttreatment themes were reduced function following revision compared to pretreatment function. Of the 301 patients, 199 (66%) had nonoperative care, with remission for 169 (85%); 40 (13%) had one-stage reimplantation and 36 (90%) had infection remission; 16 (5%) had two-stage reimplantation with remission in 14 (87%); and 46 (16%) had debridement and implant retention, with remission for 38 (83%). The matrix showed that patients with infected HRA preferred nonoperative care, which was successful for 85%. Qualitative themes found less patient distress with nonoperative treatment and the greatest patient distress with two-stage revision.


Antibacterial activity of Omani honey alone and in combination with gentamicin.
To investigate the anti-Staphylococcal activity of Omani honey, gentamicin and combination of the 2. This study was conducted in the Laboratories of the Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman in 2004. Thirty honey samples from different parts of Oman were investigated for their activity against Staphylococcus aureus, using an agar well diffusion technique. The honey sample giving the best anti-staphylococcal activity was selected and further investigated for the killing rate on its own and in combination with gentamicin using tube dilution technique. Marked variations in the antibacterial activity of the different honey samples were observed. Thirteen of the Omani honey samples (43%) showed excellent anti Staphylococcus aureus activity. The best of the excellent honey samples (OH26), at a concentration of 50%, showed killing rate of 38% of Staphylococcus aureus at 30 minutes and 45% at one hour. Gentamicin (at 4 microg/ml) killed 70% and 88% while the rate of killing for the combination of honey and gentamicin was superior with 92% and 93% killing in the same duration. Omani honey, in-vitro, possess anti-Staphylococcus aureus activity, which enhances gentamicin activity by 22% in the early phases of interaction.


An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.
The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.


Positive Association of Plasma Homocysteine Levels with Cardio-Ankle Vascular Index in a Prospective Study of Japanese Men from the General Population.
Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population. We prospectively recruited 658 participants (40-69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors. Men had higher Hcy levels and CAVI values and lower folate intake than women (all, p<0.001). At baseline, Hcy, folate intake, and the two genotypes were not associated with CAVI values for both sexes. Among men, Hcy levels were positively associated with CAVI values at the 5-year follow-up (p=0.033). Folate intake and the two genotypes were not associated with the 5-year CAVI values. Plasma Hcy may be involved in arterial stiffness progression, as monitored using CAVI, among men.


High-efficiency two-dimensional Ruddlesden-Popper perovskite solar cells.
Three-dimensional organic-inorganic perovskites have emerged as one of the most promising thin-film solar cell materials owing to their remarkable photophysical properties, which have led to power conversion efficiencies exceeding 20 per cent, with the prospect of further improvements towards the Shockley-Queisser limit for a single‐junction solar cell (33.5 per cent). Besides efficiency, another critical factor for photovoltaics and other optoelectronic applications is environmental stability and photostability under operating conditions. In contrast to their three-dimensional counterparts, Ruddlesden-Popper phases--layered two-dimensional perovskite films--have shown promising stability, but poor efficiency at only 4.73 per cent. This relatively poor efficiency is attributed to the inhibition of out-of-plane charge transport by the organic cations, which act like insulating spacing layers between the conducting inorganic slabs. Here we overcome this issue in layered perovskites by producing thin films of near-single-crystalline quality, in which the crystallographic planes of the inorganic perovskite component have a strongly preferential out-of-plane alignment with respect to the contacts in planar solar cells to facilitate efficient charge transport. We report a photovoltaic efficiency of 12.52 per cent with no hysteresis, and the devices exhibit greatly improved stability in comparison to their three-dimensional counterparts when subjected to light, humidity and heat stress tests. Unencapsulated two-dimensional perovskite devices retain over 60 per cent of their efficiency for over 2,250 hours under constant, standard (AM1.5G) illumination, and exhibit greater tolerance to 65 per cent relative humidity than do three-dimensional equivalents. When the devices are encapsulated, the layered devices do not show any degradation under constant AM1.5G illumination or humidity. We anticipate that these results will lead to the growth of single-crystalline, solution-processed, layered, hybrid, perovskite thin films, which are essential for high-performance opto-electronic devices with technologically relevant long-term stability.


Determinants of prakriti, the human constitution types of Indian traditional medicine and its correlation with contemporary science.
Constitutional type of an individual or prakriti is the basic clinical denominator in Ayurveda, which defines physical, physiological, and psychological traits of an individual and is the template for individualized diet, lifestyle counseling, and treatment. The large number of phenotype description by prakriti determination is based on the knowledge and experience of the assessor, and hence subject to inherent variations and interpretations. In this study we have attempted to relate dominant prakriti attribute to body mass index (BMI) of individuals by assessing an acceptable tool to provide the quantitative measure to the currently qualitative ayurvedic prakriti determination. The study is cross sectional, multicentered, and prakriti assessment of a total of 3416 subjects was undertaken. Healthy male, nonsmoking, nonalcoholic volunteers between the age group of 20-30 were screened for their prakriti after obtaining written consent to participate in the study. The prakriti was determined on the phenotype description of ayurvedic texts and simultaneously by the use of a computer-aided prakriti assessment tool. Kappa statistical analysis was employed to validate the prakriti assessment and Chi-square, Cramer's V test to determine the relatedness in the dominant prakriti to various attributes. We found 80% concordance between ayurvedic physician and software in predicting the prakriti of an individual. The kappa value of 0.77 showed moderate agreement in prakriti assessment. We observed a significant correlations of dominant prakriti to place of birth and BMI with Chi-square, P < 0.01 (Cramer's V-value of 0.156 and 0.368, respectively). The present study attempts to integrate knowledge of traditional ayurvedic concepts with the contemporary science. We have demonstrated analysis of prakriti classification and its association with BMI and place of birth with the implications to one of the ways for human classification.


Calpains of Leishmania braziliensis: genome analysis, differential expression, and functional analysis.
Calpains are proteins belonging to the multi-gene family of calcium-dependent cysteine peptidases that undergo tight on/off regulation, and uncontrolled proteolysis of calpains is associated with severe human pathologies. Calpain orthologues are expanded and diversified in the trypanosomatids genome. Here, we characterised calpains in Leishmania braziliensis, the main causative agent of cutaneous leishmaniasis in Brazil. In total, 34 predicted calpain-like genes were identified. After domain structure evaluation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) during in vitro metacyclogenesis revealed (i) five genes with enhanced expression in the procyclic stage, (ii) one augmented gene in the metacyclic stage, and (iii) one procyclic-exclusive transcript. Western blot analysis revealed that an antibody against a consensus-conserved peptide reacted with multiple calpain-like proteins, which is consistent with the multi-gene family characteristic. Flow cytometry and immunocytochemistry analyses revealed the presence of calpain-like molecules mainly in the cytoplasm, to a lesser extent in the plasma membrane, and negligible levels in the nucleus, which are all consistent with calpain localisation. Eventually, the calpain inhibitor MDL28170 was used for functional studies revealing (i) a leishmaniostatic effect, (ii) a reduction in the association index in mouse macrophages, (iii) ultra-structural alterations conceivable with autophagy, and (iv) an enhanced expression of the virulence factor GP63. This report adds novel insights into the domain structure, expression, and localisation of L. braziliensis calpain-like molecules.


Intensive insulin therapy for treatment of type I diabetes.
Intensive insulin therapy is best defined as a comprehensive system of diabetes management with the patient and management team as partners. The system is directed at improvement of glycemia and patient well-being. Glycemic targets should be individually defined. Frequent self-monitoring of blood glucose, probably at least four times per day, is essential for meticulous control. The benefits include improved psychosocial functioning and the potential of lessening the risks of chronic complications of diabetes. The risks relate to problems associated with hypoglycemia, which are increased if meticulous glycemic control is sought. One of the important elements of intensive therapy is a multiple-component insulin program designed to provide effective insulinemia coinciding with each major meal and continuous basal insulinemia throughout the 24-h day. This may be achieved with continuous subcutaneous insulin infusion (CSII) or multiple injections with various insulin regimens, although CSII may offer real advantages in terms of the pharmacokinetics of insulin delivery. Other pharmacokinetic issues to be considered involve selection of injection sites, timing of premeal insulin, and mixing insulins. Many studies have shown that, albeit with effort, excellent glycemic control can be achieved by various intensive insulin-therapy regimens. The implementation of a program of intensive therapy involves patient self-management in terms of altering insulin dosages, food intake, and/or activity in an attempt to achieve the target level of glycemia selected. In motivated patients willing to embark on such a course of therapy, intensive insulin therapy can be worthwhile. It should be considered for all patients with type I (insulin-dependent) diabetes mellitus.


Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. The U.S. Simulect Renal Transplant Study Group.
Basiliximab is an interleukin-2 receptor (CD25) chimeric monoclonal antibody used for acute rejection prophylaxis in renal transplants. In the context of a randomized, double-blind efficacy trial, its population pharmacokinetics and potential exposure-response relationships were explored in de novo kidney allograft recipients receiving 40 mg basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppressive therapy with cyclosporine microemulsion and corticosteroids. Serial blood samples (8.2+/-1.3 per patient) were collected over 12 weeks after transplant from 169 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. The duration of CD25 saturation was estimated as the time over which serum basiliximab concentrations exceeded 0.2 microg/ml. The relationships between pharmacokinetic parameters and demographic-clinical covariates were explored by regression methods and unpaired t-tests. Basiliximab clearance was 36.7+/-15.2 ml/hr, distribution volume 8.0+/-2.4 L, and half life 7.4+/-3.0 days. Patient weight (range, 44-131 kg) and age (range, 20-69 yrs) each contributed < or =6% to the variability in clearance and volume. Gender, ethnic group, and the presence of proteinuria had no clinically relevant influences on basiliximab disposition. Receptor-saturating basiliximab concentrations were maintained for 36+/-14 days (range, 12-91). There was no apparent relationship between the incidence or day of onset of acute rejection episodes during CD25 saturation and basiliximab concentration (range, 0.2-5.0 microg/ml). In patients who experienced a rejection episode after basiliximab was eliminated from serum (n=33), basiliximab had not been cleared faster than in their rejection-free peers (P=0.322) nor had CD25 been saturated for a shorter period of time (33+/-13 days vs. 37+/-14 days for rejection-free patients, P=0.162). There were no demographic or clinical subpopulations not adequately treated with the standard basiliximab dosing regimen. Over the range of CD25 suppression durations observed in this study, extended periods of receptor blockade did not seem to confer an immunoprophylactic advantage compared with shorter periods of receptor suppression.


Infective endocarditis caused by nutritionally variant streptococci.
Infective endocarditis caused by nutritionally variant streptococci (NVS) has a higher rate of complications than endocarditis caused by other streptococci. The bacteriologic failure rate and the mortality rate are high. However, current knowledge on this disease derives from previous patient data from 1987. Recent case reports showed successful antibiotic treatment in the absence of surgery. Here, we report the clinical outcome of infective endocarditis caused by NVS in our hospital. Data were collected by retrospective case note review. Between 1996 and 2006, there were 8 cases of NVS endocarditis: 4 patients had infection caused by Abiotrophia defectiva and 4 patients had infection caused by Granulicatella adiacens. Vegetation size on echocardiography was large (10 mm) in 7 patients, and embolization occurred in 3 patients. Patients were treated with penicillin and gentamicin initially, and 3 of them were successfully treated. The regimens were shifted to vancomycin, teicoplanin, or cefotaxime in 2 cases because of poor therapeutic responses. A total of 4 patients underwent early valve replacement successfully because of severe heart failure. Three patients underwent mitral valve repair successfully at the time of 2, 4, and 7 months after the diagnosis of endocarditis. The valve cultures at surgery were negative. There was no mortality or relapse. The bacteriologic failure rate was zero. Antibiotic treatment with penicillin and gentamicin had a high rate of success in patients with infective endocarditis caused by NVS. Early surgical intervention should be considered in those patients with deteriorating heart failure due to valve destruction.


Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation.
We evaluated the effects of exposure to high cholesterol levels for 3 h on arterial smooth muscle responses to adrenergic stimulation. Femoral arteries from Dutch belted rabbits were perfused in vitro with a constant-flow variable-pressure perfusion apparentus. After equilibration the vessels were perfused for 180 min more with media supplemented with cholesterol-phospholipid (C/PL) liposomes of molar ratios of 2:1 or 0.5:1. Although resting vascular resistance was unchanged, norepinephrine (NE) concentration-response analyses revealed a fivefold increase in NE sensitivity (P less than 0.001) in the arteries perfused with the cholesterol-enriched liposomes (2:1) compared with control arteries perfused with the 0.5:1 liposome medium. The arteries perfused with the cholesterol-enriched liposomes demonstrated a 60% increase in cholesterol content and a marked (90%) reduction in Na+-K+-ATPase activity. The increased sensitivity of the cholesterol-enriched arteries was not mediated by acute reductions in Na-pump activity, altered endothelial function, adrenergic nerve function, or prostaglandin production. Cholesterol-induced sensitization to NE did demonstrate an absolute dependence on extra-cellular calcium. These findings suggest that an increase in the free cholesterol content of the arterial smooth muscle cell plasma membrane alters membrane permeability to extracellular calcium during adrenergic stimulation.


Perceptions of Psychological Coercion and Human Trafficking in the West Midlands of England: Beginning to Know the Unknown.
Modern slavery is less overt than historical state-sanctioned slavery because psychological abuse is typically used to recruit and then control victims. The recent UK Draft Modern Slavery Bill, and current UK government anti-slavery strategy relies heavily on a shared understanding and public cooperation to tackle this crime. Yet, UK research investigating public understanding of modern slavery is elusive. We report community survey data from 682 residents of the Midlands of England, where modern slavery is known to occur, concerning their understanding of nonphysical coercion and human trafficking (one particular form of modern slavery). Analysis of quantitative data and themed categorization of qualitative data revealed a mismatch between theoretical frameworks and understanding of psychological coercion, and misconceptions concerning the nature of human trafficking. Many respondents did not understand psychological coercion, believed that human trafficking did not affect them, and confused trafficking with immigration. The public are one of the most influential interest groups, but only if well informed and motivated towards positive action. Our findings suggest the need for strategically targeted public knowledge exchange concerning this crime.


Everolimus-eluting bioresorbable vascular scaffolds for treatment of complex chronic total occlusions.
Bioresorbable vascular scaffolds (BVS) represent a novel therapeutic option for the treatment of coronary artery diseases. The objective of this study was to evaluate the feasibility of BVS implantation in complex chronic total occlusions (CTO). The present report is a multicentre registry evaluating results after BVS deployment in challenging CTO lesions, defined as J-CTO score ≥2 (difficult or very difficult). A total of 105 patients were included in the present analysis. The mean J-CTO score was 2.61 (difficult 52.4%, very difficult 47.6%). Device success and procedural success rates were 98.1% and 97.1%, respectively. The retrograde approach was used in 25.7% of cases. After wire crossing, predilatation was performed in all cases with a mean predilatation balloon diameter of 2.73±0.43 mm. The mean scaffold length was 59.75±25.85 mm, with post-dilatation performed in 89.5% of the cases and a mean post-dilatation balloon diameter of 3.35±0.44 mm. Post-PCI minimal lumen diameter was 2.50±0.51 mm and percentage diameter stenosis 14.53±10.31%. At six-month follow-up, a total of three events were reported: one periprocedural myocardial infarction, one late scaffold thrombosis and one additional target lesion revascularisation. The present report suggests the feasibility of BVS implantation in complex CTO lesions, given adequate lesion preparation and post-dilatation, with good acute angiographic results and midterm clinical outcomes.


Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children.
Our prospective cohort study of nonsmoking African-American and Dominican mothers and children in New York City is evaluating the role of prenatal exposure to urban pollutants, including polycyclic aromatic hydrocarbons (PAHs) , environmental tobacco smoke (ETS) , and pesticides, in the pathogenesis of neurobehavioral disorders. We used the Bayley Scales of Infant Development to evaluate the effects on child mental and psychomotor development of prenatal exposure to airborne PAHs monitored during pregnancy by personal air sampling. Behavioral development was assessed by the Child Behavior Checklist. We adjusted for potential confounders including sociodemographic factors and prenatal exposure to ETS and chlorpyrifos. Prenatal exposure to PAHs was not associated with psychomotor development index or behavioral problems. However, high prenatal exposure to PAHs (upper quartile) was associated with lower mental development index at age 3 [beta=-5.69; 95% confidence interval (CI), -9.05 to -2.33; p<0.01]. The odds of cognitive developmental delay were also significantly greater for children with high prenatal exposure (odds ratio=2.89; 95% CI, 1.33 to 6.25; p=0.01). General estimated equation analysis showed a significant age times PAH effect on mental development (p=0.01), confirming the age-specific regression findings. Further adjustment for lead did not alter the relationships. There were no differences in effect sizes by ethnicity. The results require confirmation but suggest that environmental PAHs at levels recently encountered in New York City air may adversely affect children's cognitive development at 3 years of age, with implications for school performance.


Microwave induced "egg yolk" structure in Cr/V-MIL-53.
Using a one pot microwave procedure, mixed-metal "egg yolk" MOFs are created, with a core of (Cr/V)-MIL-53 and a shell of Cr-MIL-53. In contrast, the solvothermal method produces homogeneous mixed-metal MOFs. The influence of Cr and V on the flexibility and breathing was studied via T-XRPD and CO2 adsorption measurements.


Seeing Central African forests through their largest trees.
Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies.


Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation.
The Mediterranean diet reduces the risk of coronary artery disease as a consequence of its high content of antioxidants, namely, hydroxytyrosol (HT) and oleuropein aglycone (OleA), typical of virgin olive oil. Because intercellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) and E-selectin are crucial for endothelial activation, the role of the phenolic extract from extra virgin olive oil (OPE), OleA, HT, and homovanillyl alcohol (HVA) on cell surface and mRNA expression in human umbilical vascular endothelial cells (HUVEC) was evaluated. OPE strongly reduced cell surface expression of ICAM-1 and VCAM-1 at concentrations physiologically relevant (IC50 < 1 microM), linked to a reduction in mRNA levels. OleA and HT were the main components responsible for these effects. HVA inhibited cell surface expression of all the adhesion molecules, whereas the effect on mRNA expression was weaker. These results supply new insights on the protective role of olive oil against vascular risk through the down-regulation of adhesion molecules involved in early atherogenesis.


The effects of corrective information about disease epidemics and outbreaks: Evidence from Zika and yellow fever in Brazil.
Disease epidemics and outbreaks often generate conspiracy theories and misperceptions that mislead people about the risks they face and how best to protect themselves. We investigate the effectiveness of interventions aimed at combating false and unsupported information about the Zika epidemic and subsequent yellow fever outbreak in Brazil. Results from a nationally representative survey show that conspiracy theories and other misperceptions about Zika are widely believed. Moreover, results from three preregistered survey experiments suggest that efforts to counter misperceptions about diseases during epidemics and outbreaks may not always be effective. We find that corrective information not only fails to reduce targeted Zika misperceptions but also reduces the accuracy of other beliefs about the disease. In addition, although corrective information about the better-known threat from yellow fever was more effective, none of these corrections affected support for vector control policies or intentions to engage in preventive behavior.


Differential gene expression in Escherichia coli during aerosolization from liquid suspension.
Comparative transcriptome analysis was used to determine the differentially expressed genes in Escherichia coli during aerosolization from liquid suspension. Isogenic mutant studies were then used to examine the potential part played by some of these genes in bacterial survival in the air. Bioaerosols were sampled after 3 min of nebulization, which aerosolized the bacteria from the liquid suspension to an aerosol chamber (A0), and after further 30 min of airborne suspension in the chamber (A30). Bacteria at A0 showed 65 differentially expressed genes (30 downregulated and 35 upregulated) as compared to the original bacteria in the nebulizer. Droplet evaporation models predicted a drop in temperature in the bioaerosols, which coincides with the change in the expression of cold shock protein genes-cspB and cspG in the bacteria. The most notable group of differentially expressed genes was sorbitol transport and metabolism genes (srlABDEMR). Other genes associated with osmotic stress, nutrient limitation, DNA damage, and other stresses were differentially expressed in the bacteria at A0. After further airborne suspension, one gene (ypfM, which encodes a hypothetical protein with unknown function) was downregulated in the bacteria at A30 as compared to those at A0. Finally, isogenic mutants with either the dps or srlA gene deleted (both genes were upregulated at A0) had lower survival than the parental strain, which is a sign of their potential ability to protect the bacteria in the air.


Titania hollow spheres modified with tungstophosphoric acid with enhanced visible light absorption for the photodegradation of 4-chlorophenol.
Titania hollow spheres were synthesized using silica nanospheres as the template. The core was removed using NaOH solution. They were subsequently impregnated with tungstophosphoric acid (TPA) solutions and annealed at two different temperatures (100 and 500 °C). These materials were characterized by several physicochemical techniques (XRD, BET, SEM, DRS, FT-IR, FT-Raman and 31P MAS-NMR). The 31P MAS-NMR and FT-IR characterization showed that the main species present in the samples was the [PW12O40]3- anion, which was partially transformed into the [P2W21O71]6- anion during the synthesis and drying step. 31P MAS-NMR, and FT-Raman characterization revealed the evidence of a strong interaction between the Keggin anion of TPA and TiO2 surfaces, possibly due to the formation of surface heteropolyacid-TiO2 complexes. The DRS results showed that the absorption threshold onset continuously shifted to the visible region with increased TPA concentration and calcination at 500 °C. The enhanced visible light absorption could be related to the formation of a surface complex TPA Keggin anion-TiO2. The catalytic activity of the materials in the photodegradation of 4-chlorophenol under UV and visible light irradiation increased when the TPA content and the calcination temperature of the samples were raised.


Identifying neuronal correlates of dying and resuscitation in a model of reversible brain anoxia.
We developed a new rodent model of reversible brain anoxia and performed continuous electrocorticographic (ECoG) and intracellular recordings of neocortical neurons to identify in real-time the cellular and network dynamics that successively emerge throughout the dying-to-recovery process. Along with a global decrease in ECoG amplitude, deprivation of oxygen supply resulted in an early surge of beta-gamma activities, accompanied by rhythmic membrane depolarizations and regular firing in pyramidal neurons. ECoG and intracellular signals were then dominated by low-frequency activities which progressively declined towards isoelectric levels. Cortical neurons during the isoelectric state underwent a massive membrane potential depolarizing shift, captured in the ECoG as a large amplitude triphasic wave known as the "wave-of-death" (WoD). This neuronal anoxic depolarization, associated with a block of action potentials and a loss of cell integrative properties, could however be reversed if brain re-oxygenation was rapidly restored (within 2-3.5 min). The subsequent slow repolarization of neocortical neurons resulted in a second identifiable ECoG wave we termed "wave-of-resuscitation" since it inaugurated the progressive regaining of pre-anoxic synaptic and firing activities. These results demonstrate that the WoD is not a biomarker of an irremediable death and unveil the cellular correlates of a novel ECoG wave that may be predictive of a successful recovery. The identification of real-time biomarkers of onset and termination of cell anoxic insult could benefit research on interventional strategies to optimize resuscitation procedures.


Tablet-Based Apps for Phonics and Phonological Awareness: Protocol for Evidence-Based Appraisal of Content, Quality, and Usability.
The use of mobile apps to manage and promote health is becoming increasingly popular. Mobile apps are gaining popularity particularly in educational and interventional settings owing to their perceived advantages including support for and engagement of individuals with reading difficulties. In the context of COVID-19, the need for technology-based tools has increased. For practitioners and educators who wish to use apps in their practice or recommend apps to individuals with reading difficulties, it is challenging to identify high-quality apps in app stores. This protocol describes a systematic search, selection, and appraisal process for tablet apps targeting phonics knowledge and phonological awareness skills. This protocol aimed to (1) provide a systematic method for identifying tablet apps targeting phonics knowledge and phonological awareness skills in the Google Play Store and Apple's App Store and (2) describe an evidence-based approach for quality appraisal of these apps by using structured tools. This protocol describes an evidence-based method guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework to systematically search, select, and appraise apps targeting phonics knowledge and phonological awareness skills, present in Google Play and the App Store. We intend to perform a systematic and comprehensive search and a 2-step process for screening: (1) broad screening (app titles) and (2) narrow screening (marketing descriptions). Quality appraisal of the included apps will involve two structured appraisal tools: (1) the Mobile Application Rating Scale and (2) the Appraising Apps for Reading Checklist. This method will help determine the number of apps targeting phonics knowledge and phonological awareness, present on the Android and iOS platforms. The content, quality, and usability of these apps will be determined using structured appraisal tools. We have planned to conduct searches on Google Play and the App Store in January-March 2021; broad and focused screening, from April 2021; and data extraction and quality appraisal in October 2021. This protocol provides a basis for locating and evaluating apps targeting phonics knowledge and phonological awareness skills. This protocol will support practitioners, educators, and families to make informed decisions when purchasing apps for instructional use. PRR1-10.2196/23921.


New evidence of the involvement of Lichtheimia corymbifera in farmer's lung disease.
Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis resulting from recurrent exposure to moldy plant materials. We investigated and compared the initial response of respiratory epithelium after exposure to extracts of Sacharopolyspora rectivirgula, Lichtheimia corymbifera (formerly Absidia corymbifera), Eurotium amstelodami and Wallemia sebi. The two criteria for selection of these species were their high prevalence in the hay handled by FLD patients and the presence of high levels of specific precipitins to these molds in FLD patients' sera. Hydrosoluble extracts were prepared from spores and hyphae grown in culture under optimal conditions for each of the four species. Confluent A549 cells were inoculated with one of the four calibrated soluble extracts. Two mediators, one inflammatory (Interleukin (IL)-8) and one allergic (IL-13), were quantified using real-time PCR and ELISA assay, after four exposure periods (30 min, 2 h, 4 h and 8 h). S. rectivirgula and L. corymbifera extracts were the only ones which induced a marked upregulation of IL-8, as shown by both real-time PCR and ELISA assay 8 h after the initial contact. This study adds to the growing body of evidence that L. corymbifera should be recognized as an etiologic agent of FLD along with S. rectivirgula.


On the role of IRS2 in the regulation of functional beta-cell mass.
The proper regulation of blood glucose homeostasis in mammals requires an adequate relation between the capacity to produce insulin and metabolic demand. Insulin receptor substrate proteins (IRS) are signalling intermediates that are required to keep this balance because they are needed for insulin action in target tissues but also for insulin production in pancreatic beta-cells. The total functional beta-cell mass in an individual sets the limit of how much insulin can be produced at a given time. It can change adaptively to meet demand and studies in vivo indicate that the regulation of beta-cell mass involves IRS2, while IRS1 is only required for proper insulin production in beta-cells. Overexpression studies in isolated islets have shown that IRS2, but not IRS1 or Shc, is sufficient to induce proliferation of beta-cells and to protect against d-glucose-induced apoptosis. In light of the finding that many growth factors can regulate Irs2 in islets, this signalling intermediate could balance capacity for insulin production with demand. This review summarizes observations in mouse models and in primary beta-cells and proposes a new hypothetical model of how IRS2 might control beta-cell mass.


Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease.
The nuclear proteasome activator REGgamma/PA28gamma is an ATP- and ubiquitin-independent activator of the 20S proteasome and has been proposed to degrade and thereby regulate both a key human oncogene, encoding the coactivator SRC-3/AIB1, and the cyclin-dependent kinase inhibitor p21 (Waf/Cip1). We report the identification and characterization of a PA28/REG homolog in Dictyostelium. Association of a recombinant Dictyostelium REG with the purified Dictyostelium 20S proteasome led to the preferential stimulation of the trypsin-like proteasome peptidase activity. Immunolocalization studies demonstrated that the proteasome activator is localized to the nucleus and is present in growing as well as starving Dictyostelium cells. Our results indicate that the Dictyostelium PA28/REG activator can stimulate both the trypsin-like and chymotrypsin-like activities of the 20S proteasome and supports the idea that the REGgamma-20S proteasome represents an early unique nuclear degradation pathway for eukaryotic cells.


Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee.
EXECUTIVE SUMMARY The "Guideline for Prevention of Surgical Site Infection, 1999" presents the Centers for Disease Control and Prevention (CDC)'s recommendations for the prevention of surgical site infections (SSIs), formerly called surgical wound infections. This two-part guideline updates and replaces previous guidelines.1,2 Part I, "Surgical Site Infection: An Overview," describes the epidemiology, definitions, microbiology, pathogenesis, and surveillance of SSIs. Included is a detailed discussion of the pre-, intra-, and postoperative issues relevant to SSI genesis. Part II, "Recommendations for Prevention of Surgical Site Infection," represents the consensus of the Hospital Infection Control Practices Advisory Committee (HICPAC) regarding strategies for the prevention of SSIs.3 Whenever possible, the recommendations in Part II are based on data from well-designed scientific studies. However, there are a limited number of studies that clearly validate risk factors and prevention measures for SSI. By necessity, available studies have often been conducted in narrowly defined patient populations or for specific kinds of operations, making generalization of their findings to all specialties and types of operations potentially problematic. This is especially true regarding the implementation of SSI prevention measures. Finally, some of the infection control practices routinely used by surgical teams cannot be rigorously studied for ethical or logistical reasons (e.g., wearing vs not wearing gloves). Thus, some of the recommendations in Part II are based on a strong theoretical rationale and suggestive evidence in the absence of confirmatory scientific knowledge.It has been estimated that approximately 75% of all operations in the United States will be performed in "ambulatory," "same-day," or "outpatient" operating rooms by the turn of the century.4 In recommending various SSI prevention methods, this document makes no distinction between surgical care delivered in such settings and that provided in conventional inpatient operating rooms. This document is primarily intended for use by surgeons, operating room nurses, postoperative inpatient and clinic nurses, infection control professionals, anesthesiologists, healthcare epidemiologists, and other personnel directly responsible for the prevention of nosocomial infections. This document does not: Specifically address issues unique to burns, trauma, transplant procedures, or transmission of bloodborne pathogens from healthcare worker to patient, nor does it specifically address details of SSI prevention in pediatric surgical practice. It has been recently shown in a multicenter study of pediatric surgical patients that characteristics related to the operations are more important than those related to the physiologic status of the patients.5 In general, all SSI prevention measures effective in adult surgical care are indicated in pediatric surgical care. Specifically address procedures performed outside of the operating room (e.g., endoscopic procedures), nor does it provide guidance for infection prevention for invasive procedures such as cardiac catheterization or interventional radiology. Nonetheless, it is likely that many SSI prevention strategies also could be applied or adapted to reduce infectious complications associated with these procedures. Specifically recommend SSI prevention methods unique to minimally invasive operations (i.e., laparoscopic surgery). Available SSI surveillance data indicate that laparoscopic operations generally have a lower or comparable SSI risk when contrasted to open operations.6-11 SSI prevention measures applicable in open operations (e.g., open cholecystectomy) are indicated for their laparoscopic counterparts (e.g., laparoscopic cholecystectomy). Recommend specific antiseptic agents for patient preoperative skin preparations or for healthcare worker hand/forearm antisepsis. Hospitals should choose from products recommended for these activitie


Diagnosis of airway obstruction in primary care in the UK: the CADRE (COPD and Asthma Diagnostic/management REassessment) programme 1997-2001.
Asthma and COPD require different management strategies, but differentiation in primary care is difficult. This primary care support initiative observed the impact of spirometry and clinical assessment on the diagnosis of airway disease. Of 61,191 patients aged > or =40 years being treated for respiratory conditions within 1003 UK primary care practices, 43,203 underwent a diagnostic review including standardized spirometric assessment. The proportion of patients in whom the diagnosis was changed by the additional information was determined. The relationship of various patient characteristics was compared with the baseline and review diagnoses and with any change in diagnosis. Asthma was initially diagnosed in 43% of patients, COPD in 35%, mixed disease in 9%, and other respiratory condition in 13%. Patients initially diagnosed with asthma, mixed disease, or another condition were more likely to have their diagnosis changed at review (54%, 46%, and 63%, respectively) than those initially diagnosed with COPD (14%). A change from asthma to COPD was associated with male gender, smoking, older age, and reduced lung function, the opposite being associated with a change from COPD to asthma. In this study, a clinical review supplemented by additional information including spirometry highlights apparent mislabeling of significant numbers of patients with chronic obstructive disease in general practice with significant implications for individual treatment and healthcare provision. This study shows that the addition of more clinical information can have a major effect on diagnostic tendency in patients with airway disease. An initial diagnosis of COPD seems less likely to change following review than an asthma diagnosis. While it is likely that greater information leads to a more accurate diagnosis, the differential effect of new information on diagnostic labeling highlights the insecurity of the diagnostic process in primary care in the UK.


Salmonella enters a dormant state within human epithelial cells for persistent infection.
Salmonella Typhimurium (S. Typhimurium) is an enteric bacterium capable of invading a wide range of hosts, including rodents and humans. It targets different host cell types showing different intracellular lifestyles. S. Typhimurium colonizes different intracellular niches and is able to either actively divide at various rates or remain dormant to persist. A comprehensive tool to determine these distinct S. Typhimurium lifestyles remains lacking. Here we developed a novel fluorescent reporter, Salmonella INtracellular Analyzer (SINA), compatible for fluorescence microscopy and flow cytometry in single-bacterium level quantification. This identified a S. Typhimurium subpopulation in infected epithelial cells that exhibits a unique phenotype in comparison to the previously documented vacuolar or cytosolic S. Typhimurium. This subpopulation entered a dormant state in a vesicular compartment distinct from the conventional Salmonella-containing vacuoles (SCV) as well as the previously reported niche of dormant S. Typhimurium in macrophages. The dormant S. Typhimurium inside enterocytes were viable and expressed Salmonella Pathogenicity Island 2 (SPI-2) virulence factors at later time points. We found that the formation of these dormant S. Typhimurium is not triggered by the loss of SPI-2 effector secretion but it is regulated by (p)ppGpp-mediated stringent response through RelA and SpoT. We predict that intraepithelial dormant S. Typhimurium represents an important pathogen niche and provides an alternative strategy for S. Typhimurium pathogenicity and its persistence.


Balloon dilatation for cardiac obstructive lesions in infants and children.
PBD has been used to relieve a wide variety of cardiac obstructive lesions in infancy and childhood. However, it has been most frequently used for semilunar valve stenosis, particularly PS. Results of pulmonic PBD are almost uniformly satisfactory for relief of typical PS, and the low rate of significant complications show that it is a safe procedure in practiced hands. It is now considered the treatment of choice for typical PS. Recently reported results of PBD for critical neonatal PS are also encouraging. New generations of balloon catheters better suited for neonatal balloon valvuloplasty will probably facilitate the procedure. In contrast, results for dysplastic valves are poor, suggesting that this condition is not amenable to PBD. Aortic stenosis also responds well to PBD in infancy and childhood when the valve is not dysplastic. The procedure in general is technically more difficult than pulmonary valvuloplasty, with a higher rate of complications, especially in neonates.


Advancing the integration of multi-marker metabarcoding data in dietary analysis of trophic generalists.
The application of DNA metabarcoding to dietary analysis of trophic generalists requires using multiple markers in order to overcome problems of primer specificity and bias. However, limited attention has been given to the integration of information from multiple markers, particularly when they partly overlap in the taxa amplified, and vary in taxonomic resolution and biases. Here, we test the use of a mix of universal and specific markers, provide criteria to integrate multi-marker metabarcoding data and a python script to implement such criteria and produce a single list of taxa ingested per sample. We then compare the results of dietary analysis based on morphological methods, single markers, and the proposed combination of multiple markers. The study was based on the analysis of 115 faeces from a small passerine, the Black Wheatears (Oenanthe leucura). Morphological analysis detected far fewer plant taxa (12) than either a universal 18S marker (57) or the plant trnL marker (124). This may partly reflect the detection of secondary ingestion by molecular methods. Morphological identification also detected far fewer taxa (23) than when using 18S (91) or the arthropod markers IN16STK (244) and ZBJ (231), though each method missed or underestimated some prey items. Integration of multi-marker data provided far more detailed dietary information than any single marker and estimated higher frequencies of occurrence of all taxa. Overall, our results show the value of integrating data from multiple, taxonomically overlapping markers in an example dietary data set.