Hair Regrowth with Cannabidiol (CBD)-rich Hemp Extract - A Case Series.
Androgenetic alopecia (AGA) is the most common cause of hair loss. Several FDA approved medications are available but offer limited results. Studies have shown that the endocannabinoid system (ECS) is a key player in hair follicle cell growth. The ECS cannabinoid type one (CB1) receptors are well expressed in the hair follicle cells. Cannabidiol CBD is a negative allosteric modulator of the CB1 receptor and has been shown to result in hair shaft elongation. In addition, the hair follicle cycle phases are controlled by the ECS vanilloid receptor-1 (TRPV1). CBD has also been shown to increase Wnt signaling pathways that are involved in the differentiation of dermal progenitor cells into new hair follicles and maintaining the anagen phase of the hair cycle. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase via a receptor known as vanilloid receptor-4 (TRPV4). Topical application of CBD reaches hair follicles where it is a CB1 negative modulator, and TRPV1, and TRPV4 agonist. A study was done of 35 subjects with AGA using a once daily topical hemp oil formulation, averaging about 3-4 mg per day of CBD and minimal amounts of other cannabinoids for six months. A hair count of the greatest area of alopecia was carried out before treatment and again after six months. The results revealed that men did slightly better than women, and the vertex area did better than the temporal areas. On average there was statistically significant 93.5% increase in hair after 6 months. All subjects had some regrowth. There were no reported adverse effects. Since the CBD works through novel mechanisms different from finasteride and minoxidil it can be used in conjunction with these current drugs and would be expected to have synergistic effects.


Neurocysticercosis and movement disorders: A literature review.
Neurocysticercosis (NCC) is a specific form of cysticercosis that affects the central nervous system. It is caused by the tapeworm Taenia solium, which is often found in pigs. NCC is considered one of the "great simulator/mimickers" of other diseases. In this context, movement disorders (MDs) can occur in a small percentage of individuals with NCC. This review aims to evaluate the clinicoepidemiological profile, pathological mechanisms, and historical features of NCC-associated MD. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 71 reports containing 148 individuals who developed an MD related to NCC were identified. NCC-associated MD included parkinsonism (n = 47), ataxia (n = 32), chorea (n = 18), dystonia (n = 13), tremor (n = 8), myokymia (n = 6), myoclonus (n = 4), ballism (n = 1), tics (n = 1), and others (n = 18). The mean and median ages were 36.58 (standard deviation: 20.51) and 35 years (age range: 1-88 years), respectively. There was a slight predominance of female sex (52.17%). On follow-up, 58.90% of the individuals had a full recovery; two deaths were reported. We believe that the majority of cases reported were only diagnosed because patients had classical clinical manifestations generally investigated by neuroimaging, resulting in incidental findings suggestive of NCC, which were later supported by laboratory examinations. Therefore, the association between NCC and MD is probably underreported. Clinicians should be wary of this association, mainly in endemic areas for cysticercosis.


Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke.
Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6-12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI-FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways.


A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.
We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules' expression, which might further explain the robust adjuvantation of this liposome-based vaccine.


A Bi-Dimensional Taxonomy of Social Responsivity in Middle Childhood: Prosociality and Reactive Aggression Predict Externalizing Behavior Over Time.
Developing social skills is essential to succeed in social relations. Two important social constructs in middle childhood, prosocial behavior and reactive aggression, are often regarded as separate behaviors with opposing developmental outcomes. However, there is increasing evidence for the co-occurrence of prosociality and aggression, as both might indicate responsivity to the social environment. Here, we tested whether a bi-dimensional taxonomy of prosociality and reactive aggression could predict internalizing and externalizing problems over time. We re-analyzed data of two well-validated experimental tasks for prosociality (the Prosocial Cyberball Game) and reactive aggression (the Social Network Aggression Task) in a developmental population sample (n = 496, 7-9 years old). Results revealed no associations between prosociality and reactive aggression, confirming the independence of those constructs. Interestingly, although prosociality and reactive aggression independently did not predict problem behavior, the interaction of both was negatively predictive of changes in externalizing problems over time. Specifically, only children who scored low on both prosociality and reactive aggression showed an increase in externalizing problems 1 year later, whereas levels of externalizing problems did not change for children who scored high on both types of behavior. Thus, our results suggest that at an individual level, reactive aggression in middle childhood might not always be maladaptive when combined with prosocial behavior, thereby confirming the importance of studying social competence across multiple dimensions.


GRIN2A mutations cause epilepsy-aphasia spectrum disorders.
Epilepsy-aphasia syndromes (EAS) are a group of rare, severe epileptic encephalopathies of unknown etiology with a characteristic electroencephalogram (EEG) pattern and developmental regression particularly affecting language. Rare pathogenic deletions that include GRIN2A have been implicated in neurodevelopmental disorders. We sought to delineate the pathogenic role of GRIN2A in 519 probands with epileptic encephalopathies with diverse epilepsy syndromes. We identified four probands with GRIN2A variants that segregated with the disorder in their families. Notably, all four families presented with EAS, accounting for 9% of epilepsy-aphasia cases. We did not detect pathogenic variants in GRIN2A in other epileptic encephalopathies (n = 475) nor in probands with benign childhood epilepsy with centrotemporal spikes (n = 81). We report the first monogenic cause, to our knowledge, for EAS. GRIN2A mutations are restricted to this group of cases, which has important ramifications for diagnostic testing and treatment and provides new insights into the pathogenesis of this debilitating group of conditions.


Human sperm bioassay for reprotoxicity testing in embryo culture media: some practical considerations in reducing the assay time.
Human sperm assay (HSA) is a preferred in house quality control and proficiency test (PT) practiced in fertility laboratories. HSA is performed over varying durations, apparently without following set criteria. To better understand the assay time required for reprotoxicity testing in embryo culture media, we compared American-Association-of-Bioanalysts-(AAB-) administered HSA data to our own assay performed using PT samples obtained from AAB. Participating laboratories were required to culture sperm for 48 hours to determine media acceptability. Conclusions drawn from 48- and 24-hour observations were the same, suggesting that HSA could identify reprotoxic media in less time than required by AAB. Our assay revealed that changes in motility grade in adulterated media are significantly different from those in control media. Furthermore, grade changes can be identified earlier than differences in motility loss between samples. Analyzing motility and motility quality together provides a method for establishing an optimal time for HSA.


Adhesion of dry and wet electrostatic capture silk of uloborid spider.
We demonstrate the impressive adhesive qualities of uloborid spider orb-web capture when dry, which are lost when the nano-filament threads are wetted. A force sensor with a 50 nN-1 mN detection sensitively allowed us to measure quantitatively the stress-strain characteristics of native silk threads in both the original dry state and after wetting by controlled application of water mist with droplet sizes ranging between 3 and 5 μm and densities ranging between 10(4) and 10(5) per mm(3). Stress forces of between 1 and 5 μN/μm(2) in the native, dry multifilament thread puffs were reduced to between 0.1 and 0.5 μN/μm(2) in the wetted collapsed state, with strain displacements reducing from between 2 and 5 mm in the dry to 0.10-0.12 mm in the wetted states. We conclude that wetting cribellate threads reduce their van der Waals adhesion with implications on the thread's adhesive strength under tension. This should be considered when discussing the evolutionary transitions of capture silks from the ancestral dry-state nano-filaments of the cribellate spider taxa to the wet-state glue-droplets of the ecribellate taxa.


Disease-associated change in an amphibian life-history trait.
Emerging pathogens can drive evolutionary shifts in host life-history traits, yet this process remains poorly documented in vertebrate hosts. Amphibian chytridiomycosis, caused by infection with the fungal pathogen Batrachochytrium dendrobatidis (Bd), is the worst recorded wildlife disease and has caused the extinction of over 100 species across multiple continents. A similar number of additional species have experienced mass declines and Bd remains a major source of mortality in many populations of declined species now persisting with the pathogen. Life-history theory predicts that increased extrinsic mortality in Bd-infected populations may alter amphibian life-history traits, but this has not been examined. Here, we investigate whether population Bd status is associated with age and size at maturity by comparing long-exposed Bd-infected populations, Bd-free populations, and museum specimens collected prior to Bd emergence for the endangered Australian frog Litoria verreauxii alpina. We show that Bd-infected populations have a higher proportion of males that mature at 1 year of age, and females that mature at 2 years of age, compared to Bd-free populations. Earlier maturation was associated with reduced size at maturity in males. Consistent with life-history theory, our findings may represent an adaptive evolutionary shift towards earlier maturation in response to high Bd-induced mortality. To our knowledge, this study provides the first evidence for a post-metamorphic Bd-associated shift in an amphibian life-history trait. Given high mortality in other Bd-challenged species, we suggest that chytridiomycosis may be a substantial new selection pressure shaping life-history traits in impacted amphibian species across multiple continents.


Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid-range ejection fraction.
Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (<40%, HFrEF) and with HF with preserved ejection fraction (>50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40-49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF, respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV- patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV- patients. Kaplan-Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV- of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV- patients diverged only after 18 months.


Inositol-requiring enzyme-1 regulates phosphoinositide signaling lipids and macrophage growth.
The ER-bound kinase/endoribonuclease (RNase), inositol-requiring enzyme-1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1's one known, specific RNA target, X box-binding protein-1 (XBP1) or the RNA substrates of IRE1-dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide-derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross-talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1's RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P3 ) 5-phosphatase-2 (INPPL1) is a direct target of miR-2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3 /PIP2 ratio and anabolic mTOR signaling by the IRE1-induced miR-2137 demonstrates how the ER can provide a critical input into cell growth decisions.


How does the amount of surgical insult affect bone around moving teeth?
The purpose of this study was to determine how the amount of surgical insult affects the quantity and maturity of dentoalveolar bone around teeth that have been orthodontically moved. A split-mouth design with 8 foxhound dogs was used to evaluate bone surrounding maxillary second premolars that were protracted for 15 days and retained for 7 weeks. The maxillary first premolars were extracted, and the interseptal bone was removed to within 1 mm of the second premolars; on the insult (lesser surgical insult) side, buccal and lingual vertical grooves were made in the extraction socket to undermine the mesial root of the second premolar; the insult+ (greater surgical insult) side was flapped and had modified corticotomies extending to, but not through, the lingual cortex 1 mm distal to the distal root, and 3 to 5 mm apical to both roots. Microcomputed tomography analyses were used to evaluate the material density, bone volume fraction, and trabecular characteristics of surrounding bone. Hematoxylin and eosin sections were used to determine osteoclast numbers, bone surface areas, and bone volumes. After 7 weeks of consolidation, there was significantly (P <0.05) less bone on the insult+ side; it was less dense and less mature than the bone on the insult side. Relative to the control bone, bone on the insult+ side was significantly less dense but showed no differences in bone volume. Preliminary histologic evaluations indicated increased numbers of osteoclasts and greater bone surface areas on the insult+ side than the insult side, but no differences in bone volume. Increased surgical insults produce less dense and less mature bone but have no effect on bone volume at 9 weeks after surgery.


Interferon-γ-inducible Rab20 regulates endosomal morphology and EGFR degradation in macrophages.
Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon-γ (IFN-γ) treatment. Moreover, IFN-γ and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2-positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune activation of macrophages.


Study of the Reynolds Number Effect on the Process of Instability Transition Into the Turbulent Stage.
The results of the experimental study of the Reynolds number effect on the process of the Rayleigh-Taylor (R-T) instability transition into the turbulent stage are presented. The experimental liquid layer was accelerated by compressed gas. Solid particles were scattered on the layer free surface to specify the initial perturbations in some experiments. The process was recorded with the use of a high-speed motion picture camera. The following results were obtained in experiments: (1) Long-wave perturbation is developed at the interface at the Reynolds numbers Re < 104. If such perturbation growth is limited by a hard wall, the jet directed in gas is developed. If there is no such limitation, this perturbation is resolved into the short-wave ones with time, and their growth results in gas-liquid mixing. (2) Short-wave perturbations specified at the interface significantly reduce the Reynolds number Re for instability to pass into the turbulent mixing stage.


Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial.
This international, multicenter double-blind trial was designed to compare the therapeutic profile of an atypical antipsychotic, olanzapine, with that of a conventional dopamine D2 antagonist, haloperidol. A total of 1,996 patients at 174 sites in Europe and North America were randomly assigned to treatment with olanzapine (N = 1,336) or haloperidol (N = 660) over 6 weeks. The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS). Secondary analyses included comparisons of the mean change in positive and negative symptoms, comorbid depression, extrapyramidal symptoms, and overall drug safety. Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure, including depression. Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events. Substantially more olanzapine-treated patients (66.5%) than haloperidol-treated patients (46.8%) completed 6 weeks of therapy. Statistically significant advantages of olanzapine treatment were related to 1) change in negative symptoms, 2) extrapyramidal symptom profile, 3) effect on prolactin levels, and 4) response rate. Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology, with a substantially more favorable safety profile, than haloperidol. It meets several of the criteria for a novel atypical antipsychotic agent.


Correlation of Radiological and Endoscopic Findings in Patients Presenting with Dysphagia.
Dysphagia is a common symptom with diverse etiology in otolaryngology. In the present study clinicopathological, radiological and endoscopic evaluation of patients was done in a tertiary care hospital in patients presenting with dysphagia. A prospective nonrandomized observational study was carried out on total of 80 cases having dysphagia during March 2015 to August 2016. In the present study, out of 80 patients, youngest case was a three years old child while oldest case was an 85 years old female. The mean age was 48.3 ± 20.3 years. The majority of cases were in age group 41-59 years (35%). Male to female ratio was 2.33:1. The mean duration of illness was 15.44 weeks. 15% of patients had absolute dysphagia. For detecting the lesion, Barium swallow study (BSS) showed a total sensitivity of 49.05% (n = 53), Computerised Tomography (CT) showed a total sensitivity of 85.70% (n = 49), plain skiagram neck & chest showed a total sensitivity of 88.88% (n = 9) and endoscopy was the most sensitive test overall as it showed a total sensitivity of 98.75% (n = 80). No complications were reported with either rigid or flexible endoscopy. Dysphagia is a common presenting complaint in otolaryngology with cases coming directly or being referred from other specialities. Males are more commonly affected than females and incidence of malignancy increases with age. Endoscopy can become the first screening test in dysphagia due to its high sensitivity and low risk of complications, with radiological tests being done in an adjunct manner.


Supervisee self-disclosure: a clinical psychology perspective.
Clinical supervision is a multi-functional intervention within numerous psychotherapeutic professions, including clinical psychology. It often relies on supervisees' verbal disclosures of pertinent information. There is limited research on supervisee self-disclosure in the UK, and none using clinical psychology populations. This study aimed to address the limitations in the evidence base. It used a constructivist grounded theory methodology to investigate qualified UK clinical psychologists' use of self-disclosure in supervision in order to develop a theoretical understanding of their self-disclosure processes. Ten clinical psychologists from various time points across the career span were recruited to the study. Four core conceptual categories were identified in the analysis as being integral to participants' decision-making processes: 'Setting the Scene', 'Supervisory Relationship', 'Using Self-disclosure' and 'Reviewing Outcome of Self-disclosure'. These four categories are comprised of a number of subcategories. The study's findings are compared with the current literature base, and it is argued that there are tensions with the scientist-practitioner model as it could be interpreted to encourage an expert stance, which may limit the self-disclosure of qualified supervisees. The implications of this perspective are discussed. Supervision is a key process in supporting qualified clinical psychologists and the use of disclosure appears to be important in facilitating useful supervision. It appears that clinical psychologists go through a number of complex processes in deciding whether to self disclose.


Pathogenic stromal cells as therapeutic targets in joint inflammation.
Knowledge of how the joint functions as an integrated unit in health and disease requires an understanding of the stromal cells populating the joint mesenchyme, including fibroblasts, tissue-resident macrophages and endothelial cells. Knowledge of the physiological and pathological mechanisms that involve joint mesenchymal stromal cells has begun to cast new light on why joint inflammation persists. The shared embryological origins of fibroblasts and endothelial cells might shape the behaviour of these cell types in diseased adult tissues. Cells of mesenchymal origin sustain inflammation in the synovial membrane and tendons by various mechanisms, and the important contribution of newly discovered fibroblast subtypes and their associated crosstalk with endothelial cells, tissue-resident macrophages and leukocytes is beginning to emerge. Knowledge of these mechanisms should help to shape the future therapeutic landscape and emphasizes the requirement for new strategies to address the pathogenic stroma and associated crosstalk between leukocytes and cells of mesenchymal origin.


Tropical forests and global atmospheric change: a synthesis.
We present a personal perspective on the highlights of the Theme Issue 'Tropical forests and global atmospheric change'. We highlight the key findings on the contemporary rate of climatic change in the tropics, the evidence-gained from field studies-of large-scale and rapid change in the dynamics and biomass of old-growth forests, and evidence of how climate change and fragmentation can interact to increase the vulnerability of plants and animals to fires. A range of opinions exists concerning the possible cause of these observed changes, but examination of the spatial 'fingerprint' of observed change may help to identify the driving mechanism(s). Studies of changes in tropical forest regions since the last glacial maximum show the sensitivity of species composition and ecology to atmospheric changes. Model studies of change in forest vegetation highlight the potential importance of temperature or drought thresholds that could lead to substantial forest decline in the near future. During the coming century, the Earth's remaining tropical forests face the combined pressures of direct human impacts and a climatic and atmospheric situation not experienced for at least 20 million years. Understanding and monitoring of their response to this atmospheric change are essential if we are to maximize their conservation options.


Immunoglobulins and the X-chromosome.
Serum levels of immunoglobulins (Ig) G, M, and A were determined in 28 women with an additional X-chromosome (XXX), and in equal numbers of age-matched normal women and men. Mean IgM levels were found to be highest in the XXX group, intermediate in normal women, and lowest in men; these differences were statistically significant. Mean IgM values obtained from seven XXY and three XXXY cases were almost identical with those of normal women and XXX women respectively. No such sex linkage was observed for IgA and IgG levels. These results support the suggestion that the serum level of IgM is related to the number of X chromosomes present.


Hospital length of stay and all-cause 30-day readmissions among high-risk Medicaid beneficiaries.
This study examined the association between index hospitalization characteristics and the risk of all-cause 30-day readmission among high-risk Medicaid beneficiaries using multilevel analyses. A retrospective cohort with a baseline and a follow-up period was used. The study population consisted of Medicaid beneficiaries (21-64 years old) with selected chronic conditions, continuous fee-for-service enrollment through the observation period, and at least 1 inpatient encounter during the follow-up period (N = 15,806). The outcome of 30-day readmission was measured using inpatient admissions within 30-days from the discharge date of the first observed hospitalization. Key independent variables included length of stay, reason for admission, and month of index hospitalization (seasonality). Multilevel logistic regression that accounted for beneficiaries nested within counties was used to examine this association, after controlling for patient-level and county-level characteristics. In this study population, 16.7% had all-cause 30-day readmissions. Adults with greater lengths of stay during the index hospitalization were more likely to have 30-day readmissions (adjusted odds ratio [AOR]: 1.03, 95% confidence interval [CI]: 1.02-1.04). Adults who were hospitalized for cardiovascular conditions (AOR: 1.20, 95% CI: 1.08-1.33), diabetes (AOR: 1.23, 95% CI: 1.10-1.39), cancer (AOR: 1.55, 95% CI: 1.26-1.90), and mental health conditions (AOR: 2.17, 95% CI: 1.98-2.38) were more likely to have 30-day readmissions compared to those without these conditions.


Low-cost, low-input RNA-seq protocols perform nearly as well as high-input protocols.
Recently, a number of protocols extending RNA-sequencing to the single-cell regime have been published. However, we were concerned that the additional steps to deal with such minute quantities of input sample would introduce serious biases that would make analysis of the data using existing approaches invalid. In this study, we performed a critical evaluation of several of these low-volume RNA-seq protocols, and found that they performed slightly less well in per-gene linearity of response, but with at least two orders of magnitude less sample required. We also explored a simple modification to one of these protocols that, for many samples, reduced the cost of library preparation to approximately $20/sample.


Effects of ventilation and isoflurane end-tidal concentration on intracranial and cerebral perfusion pressures in horses.
To measure the effects of isoflurane end-tidal concentration and mode of ventilation (spontaneous vs controlled) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in horses. adult horses of various breeds. Anesthesia was induced and maintained with isoflurane in O2 in 6 healthy, unmedicated, adult horses. Using a subarachnoid strain gauge transducer, ICP was measured. Blood gas tensions and carotid artery pressures also were measured. Four isoflurane doses were studied, corresponding to the following multiples of the minimum alveolar concentration (MAC): 1.0 MAC, 1.2 MAC, 1.4 MAC, and 1.6 MAC. Data were collected during controlled ventilation and spontaneous ventilation at each dose. increasing isoflurane end-tidal concentration induced significant dose-dependent decreases in mean arterial pressure (MAP) and CPP but no change in ICR Hypercapnic spontaneous ventilation caused significant increases in MAP and ICR compared with normocapnic controlled ventilation; no change in CPP was observed. Hypercapnia likely increases cerebral blood flow (CBF) by maintaining CPP in the face of presumed cerebral vasodilation in healthy anesthetized horses. The effect of isoflurane dose on CBF however, remains unresolved because it depends on the opposing influences of a decrease in CCP and cerebral vasodilation.


Single-wall carbon nanotube coating on a pyroelectric detector.
Carbon single-wall nanotubes (SWNTs) are studied as the thermal-absorption coating on a large area pyroelectric detector. The SWNTs were produced by a laser vaporization method and dispersed onto the detector surface by use of a simple airbrush technique. The detector was based on a 1-cm-diameter, 60-microm-thick lithium tantalate disk having nickel electrodes. We report the spectral responsivity of the detector ranging from 600 to 1800 nm, as well as the spatial and directional uniformity at 850 nm. Using Drude and Lorentzian dielectric functions and an effective medium approximation to obtain the indices of refraction of semiconductor and metallic SWNTs, we compared the expected theoretical relative responsivity for the two types of tube with the measured relative responsivity of the detector. Values of thermal conductivity, specific heat, and damage threshold obtained from the literature are compared with properties of alternatives for thermal coatings such as gold-black and carbon-based paint.


Stripe instability in thin films of smectic liquid-crystal polymers.
Two-dimensional nanostripes are formed in thin films of side-chain liquid-crystalline polymer films when the material enters the smectic phase. The structure is investigated using transmission electron microscopy. Electron diffraction patterns show that the chain molecules are mostly aligned in the film plane and the average molecular director is parallel to the direction of the stripes. We discuss factors affecting the stripe amplitude and periodicity, such as the film thickness and the temperature of annealing in the nematic phase, and suggest a possible mechanism for their formation. We propose that an equilibrium instability occurs due to a competition between the layer-aligning effect of the substrate and the planar director alignment, forcing smectic layers perpendicular to the film surface. The stripes decorate the overall patterns of nematic director in the polymer film and provide a means of high-resolution imaging for observation of textures and disclinations.


Hemoglobin A1c Levels Predicts Acute Kidney Injury after Coronary Artery Bypass Surgery in Non-Diabetic Patients.
Elevated hemoglobin A1c levels in patients with diabetes mellitus have been known as a risk factor for acute kidney injury after coronary artery bypass grafting. However, the relationship between hemoglobin A1c levels in non-diabetics and acute kidney injury is under debate. We aimed to investigate the association of preoperative hemoglobin A1c levels with acute kidney injury in non-diabetic patients undergoing isolated coronary artery bypass grafting. 202 non-diabetic patients with normal renal function (serum creatinine <1.4 mg/dl) who underwent isolated coronary bypass were analyzed. Hemoglobin A1c level was measured at the baseline examination. Patients were separated into two groups according to preoperative Hemoglobin A1c level. Group 1 consisted of patients with preoperative HbA1c levels of < 5.6% and Group 2 consisted of patients with preoperative HbA1c levels of ≥ 5.6%. Acute kidney injury diagnosis was made by comparing baseline and postoperative serum creatinine to determine the presence of predefined significant change based on the Kidney Disease Improving Global Outcomes (KDIGO) definition. Acute kidney injury occurred in 19 (10.5%) patients after surgery. The incidence of acute kidney injury was 3.6% in Group 1 and 16.7% in Group 2. Elevated baseline hemoglobin A1c level was found to be associated with acute kidney injury (P=0.0001). None of the patients became hemodialysis dependent. The cut off value for acute kidney injury in our group of patients was 5.75%. Our findings suggest that, in non-diabetics, elevated preoperative hemoglobin A1c level may be associated with acute kidney injury in patients undergoing coronary artery bypass grafting. Prospective randomized studies in larger groups are needed to confirm these results.


Parental psychopathology and socioeconomic position predict adolescent offspring's mental health independently and do not interact: the TRAILS study.
Familial risk factors have been implicated in the development of mental health problems in adolescents. Whether the associations between parental loading, as assessed by lifetime psychopathology, and offspring internalising and externalising problems were moderated by family socioeconomic position (SEP) was investigated. Two hypotheses of moderation were tested: (1) the "social push" hypothesis in which parental loading effects are stronger in contexts with low environmental risks and (2) the "vulnerability" hypothesis in which parental loading effects are stronger in high-risk environments. In a population-based sample of 2149, familial loading and family SEP were assessed at baseline by parent reports. Offspring psychopathology was assessed by reports from multiple informants (parent, self and teachers). Multiple linear regression was used to assess the independent associations of parental loading and family SEP on offspring psychopathology and their potential interaction. Both family SEP and familial loading had significant independent main effects on offspring internalising and externalising problems. However, the interaction terms were not significant and did not add any explanatory power to the model. Lower levels of family SEP appear not to confer additional risks for mental health problems in offspring of parents with high loading on psychopathology. During early adolescence, parental psychopathology and low family SEP seem independent risk factors for offspring mental health problems. Results do not support either the social push or vulnerability hypothesis as no evidence of interactions between parental loading and family SEP were found.


Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population.
Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD. The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [ HLA - DP / DQ ] genes) was also estimated. Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]). Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.


Study of highly selective and efficient thiol derivatization using selenium reagents by mass spectrometry.
This paper reports a systemic mass spectrometry (MS) investigation of a novel strategy for labeling biological thiols, involving the cleavage of the Se-N bond by thiol to form a new Se-S bond. Our data show that the reaction is highly selective, rapid, reversible, and efficient. Among 20 amino acids, only cysteine is reactive toward Se-N containing reagents and the reaction occurs in seconds. With the addition of dithiothreitol, peptides derivatized by selenium reagents can be recovered. The high reaction selectivity and reversibility provide potential in both selective identification and isolation of thiols from mixtures. Also, with dependence on the selenium reagent used, derivatized peptide ions exhibit tunable dissociation behaviors (either facile cleavage or preservation of the formed Se-S bond upon collision-induced dissociation), a feature that is useful in proteomics studies. Equally importantly, the thiol derivatization yield is striking, as reflected by 100% conversion of protein beta-lactoglobulin A using ebselen within 30 s. In addition, preliminary applications such as rapid screening of thiol peptides from mixtures and identification of the number of protein free and bound thiols have been demonstrated. The unique selenium chemistry uncovered in this study would be valuable in the MS analysis of thiols and disulfide bonds of proteins/peptides.


Outcomes of guided imagery in patients receiving radiation therapy for breast cancer.
Guided imagery is an established intervention in integrative oncology. This study was initiated to evaluate the impact of guided imagery on patients undergoing radiation therapy for breast cancer. Eligible patients receiving guided imagery sessions were monitored via biofeedback before and after each session. Monitored measures included blood pressure, respiration rate, pulse rate, and skin temperature. In addition, the EuroQoL Group's EQ-5D questionnaire was used for subjective assessment and patient feedback was collected at the end of radiation therapy through a satisfaction survey. Measured parameters revealed statistically significant improvement from baseline, with decreases noted in respiration rate and pulse rate as well as systolic and diastolic blood pressure. Skin temperature increased, indicating more peripheral capillary flow secondary to a decrease in the sympathetic response. Overall, 86% of participants described the guided imagery sessions as helpful, and 100% said they would recommend the intervention to others. The results of this study illustrate the positive impact of guided imagery as measured through subjective and objective parameters. Improving the overall care for patients with breast cancer supports the value of incorporating practices of integrative oncology into standard practice.


Location of glomerular immune deposits, not codeposition of immunoglobulin G, influences definitive renal outcomes in immunoglobulin A nephropathy.
It has been suggested that the prognosis of immunoglobulin (IgA) nephropathy (IgAN) is adversely affected if there is codeposition of IgG in the glomeruli or if immune deposits are present in the glomerular capillary walls. We sought to understand how these variables affect clinical outcome. A total of 80 IgAN biopsies were retrospectively divided into groups: (i) IgA without IgG deposition versus IgA + IgG and (ii) immune deposits restricted to the mesangium versus mesangium and peripheral capillary walls (PCWs). The association of these groups with the composite primary outcome of renal replacement therapy, renal transplant, death or doubling of serum creatinine (SCr) concentration was determined. The change in estimated glomerular filtration rate (eGFR) was also assessed. Covariates examined were age, sex, race, SCr and proteinuria level at biopsy and at follow-up, duration of follow-up, treatment, Oxford score and presence of crescents. IgG codeposition showed a trend toward endocapillary hypercellularity (P = 0.082); there were no other baseline differences between the IgA (n = 55) and IgA + IgG (n = 25) groups. At a median follow-up time of 29 months, the combined primary outcome was reached in 24 patients, 16 with IgA and 8 with IgA + IgG (P = 0.82). Patients with immune deposits in the PCWs (n = 21) presented with higher baseline proteinuria than those with deposits limited to the mesangium (n = 59; P = 0.025), were more likely to have crescents/segmental glomerular necrosis on biopsy (P = 0.047) and were more likely to reach the combined primary outcome (P = 0.026). Biopsies with crescents/segmental glomerular necrosis were associated with endocapillary hypercellularity (P < 0.001). In this multicenter IgAN cohort, IgG co-deposition and the location of glomerular immune deposits in the PCWs were both associated with greater histologic activity on renal biopsy, but only the location of glomerular immune deposits in the PCWs was associated with a significantly increased risk for end-stage renal disease, transplant, death and/or doubling of SCr.


Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results.
Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir, deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1. Patients were randomized to receive deleobuvir 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon-α2a/ribavirin to week 24 or 48. At week 4, 73% (11/15) and 100% (17/17) of patients in the deleobuvir 400 mg and 600 mg groups achieved HCV RNA<25 IU/ml, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the deleobuvir 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon-α2a/ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%) and asthenia (31%); these were severe in approximately 3% of patients. Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen. Clinical trials.gov number NCT01132313.


Specific climate impact of passenger and freight transport.
Emissions of short-lived species contribute significantly to the climate impact of transportation. The magnitude of the effects varies over time for each transport mode. This paper compares first the absolute climate impacts of current passenger and freight transportation. Second, the impacts are normalized with the transport work performed and modes are compared. Calculations are performed for the integrated radiative forcing and mean temperature change, for different time horizons and various measures of transport work. An unambiguous ranking of the specific climate impact can be established for freight transportation, with shipping and rail having lowest and light trucks and air transport having highest specific impact for all cases calculated. Passenger travel with rail, coach or two- and three-wheelers has on average the lowest specific climate impact also on short time horizons. Air travel has the highest specific impact on short-term warming, while on long-term warming car travel has an equal or higher impact per passenger-kilometer.


Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis.
Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5-6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.


Viii. Attachment and sleep among toddlers: disentangling attachment security and dependency.
Many scholars have proposed that parent-child attachment security should favor child sleep. Research has yet, however, to provide convincing support for this hypothesis. The current study used objective measures of sleep and attachment to assess the longitudinal links between mother-child attachment security and subsequent sleep, controlling for child dependency. Sixty-two middle-class families (30 girls) were met twice, when children were 15 months (Wave 1; W1) and 2 years of age (Wave 2; W2). At W1, mother-child attachment was assessed with the observer version of the Attachment Q-Sort. At W2, children wore an actigraph monitor for 72 hr. Results indicated that children more securely attached to their mothers subsequently slept more at night and had higher sleep efficiency, and these predictions were not confounded by child dependency. These findings suggest a unique role for secure attachment relationships in the development of young children's sleep regulation, while addressing methodological issues that have long precluded consensus in this literature.


Chain-growth polyglycosylation: synthesis of linker-equipped mannosyl oligomers.
Direct syntheses of acetylated poly-mannosides can be achieved in one-step starting from a fully acetylated thioglycoside mannosyl donor using a polymerization-type strategy under the correct conditions. Under conditions that allow polymer growth from non-reducing to reducing end (N→R), different acceptor alcohols can be used as the 'terminating acceptors' to install different linkers at the reducing terminus. The efficiency is dependent on substituents of the linker, its length, temperature and choice of Lewis acid activator.


Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks.
To provide individualized risk prediction of severe adverse pregnancy outcome based on uterine artery Doppler screening at 23 weeks. Color Doppler assessment of the uterine arteries was carried out in 5121 women attending for routine care at 23 weeks in two inner-city obstetric units. The mean uterine artery pulsatility index (PI) was calculated, and the likelihood ratios in relation to PI were generated for severe adverse outcome. This was defined as fetal death, placental abruption, and delivery before 34 weeks associated with preeclampsia and birth weight less than the 10th centile. The likelihood of severe adverse pregnancy outcome increased quadratically with mean uterine artery PI. This relationship was not affected by maternal age, ethnicity, or parity. At a mean PI of 1.45, the 95th centile for our population, the likelihood ratio for severe adverse pregnancy outcome was 5. Cigarette smoking had an additional contribution to PI in predicting severe adverse outcome, roughly doubling the risk for a given PI. The individualized risk of severe adverse pregnancy outcome can be determined by uterine artery Doppler screening at 23 weeks and knowledge of cigarette smoking history. Such individualized risk would allow ultrasound resources and clinical follow-up to be tailored to the pregnant woman for the most appropriate use of antenatal care.


Association between fatty acid supplementation and prenatal stress in African Americans: a randomized controlled trial.
To test the association between docosahexaenoic acid (DHA) supplementation and perceived stress and cortisol response to a stressor during pregnancy in a sample of African American women living in low-income environments. Sixty-four African American women were enrolled at 16-21 weeks of gestation. Power calculations were computed using published standard deviations for the Perceived Stress Scale and the Trier Social Stress Test. Participants were randomized to either 450 mg per day of DHA (n=43) or placebo (n=21). At baseline and at 24 and 30 weeks of gestation, perceived stress was assessed by self-report. Cortisol response to a controlled stressor, the Trier Social Stress Test was measured from saliva samples collected upon arrival to the laboratory and after the completion of the Trier Social Stress Test. Women in the DHA supplementation group reported lower levels of perceived stress at 30 weeks of gestation, controlling for depression and negative life events (mean 27.4 compared with 29.5, F [3, 47] 5.06, P=.029, Cohen's d=0.65). Women in the DHA supplementation had lower cortisol output in response to arriving to the laboratory and a more modulated response to the stressor (F [1.78, 83.85] 6.24, P=.004, Cohen's d=0.76). Pregnant women living in urban low-income environments who received DHA reported reduced perceived stress and lower levels of stress hormones in the third trimester. Docosahexaenoic acid supplementation may be a method for attenuating the effects of maternal stress during late pregnancy and improving the uterine environment with regard to fetal exposure to glucocorticoids. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01158976.


Associations between cardiometabolic risks and physical activity in early adulthood: a cross-sectional study.
Young adults' physical activity (PA) is a foundation of creating future healthy lifestyles. The purpose of this study was to explore differences in PA, sedentary behaviour, walkability and health beliefs among young adults with different levels of cardiometabolic risks and the influence of moderate-to-vigorous PA. A cross-sectional study was conducted using a structured questionnaire. Totally, 1149 valid responses were received for a response rate of 86.32%. According to the self-reported worst health condition, participants were categorised into healthy adults, and adults at levels 1 (overweight), 2 (obese), 3 (hypertensive, hyperlipidaemic, and/or hyperglycaemic), and 4 (with a diagnosis of cardiometabolic diseases) of cardiometabolic risks. PA, sedentary time, walkability and health beliefs. Significant differences in PA (F=3.78, p<0.01) and sedentary time (F=2.39, p<0.05) among groups with various cardiometabolic risk levels were found. Healthy adults and adults at level 1 risk had significantly higher PA than adults at risk levels 2 and 3. Young adults at risk level 3 were less likely to participate in moderate-to-vigorous PA than were healthy adults (OR=0.64 (95% CI 0.41 to 0.99), p<0.05). Individuals who perceived that there were more recreational facilities (OR=1.27 (1.05 to 1.53), p<0.05), who had higher benefits of exercise (OR=1.73 (1.30 to 2.31), p<0.001), and who had lower barriers to exercise (OR=0.42 (0.32 to 0.55), p<0.001) were more likely to participate in moderate-to-vigorous PA. Being aware of body weight changes could be a danger sign of a lack of PA. Developing environmental and psychological strategies to promote engaging in PA is necessary to promote the cardiometabolic health of young adults.


An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis.
A total of 136 Borrelia burgdorferi sensu latu strains from various biological sources (ticks, human skin, and cerebrospinal fluid) and geographical sources (Europe and North America) were investigated by Western blot (immunoblot) with eight monoclonal antibodies against different epitopes of the outer surface protein A (OspA). On the basis of the differential reactivities of these monoclonal antibodies, seven OspA serotypes were defined. As determined by 16S rRNA sequence analysis, these serotypes correlated well with recently delineated genospecies: serotype 1 corresponds to B. burgdorferi sensu strictu, serotype 2 corresponds to group VS461, and serotypes 3 to 7 correspond to Borrelia garinii sp. nov. (G. Baranton, D. Postic, I. Saint Girons, P. Boerlin, J.-C. Piffaretti, M. Assous, and P. A. D. Grimont, Int. J. Syst. Bacteriol. 42:378-383, 1992). Antigenic differences were confirmed by partial sequence analysis of OspA of representatives of each serotype. Comparative sequence analysis suggested that serotype 5 OspA resulted from genetic recombination of serotype 4 and 6 ospA genes. Serotype 2 (group VS461) was most prevalent among European skin isolates (49 of 62 isolates). Among all B. garinii strains included in this study, serotype 6 was most frequently found in ticks and only rarely in human skin and cerebrospinal fluid, whereas serotypes 4 and 5 were isolated from patients but never from ticks. Our data suggest different pathogenic potentials and organotropisms of distinct OspA serotypes and raise the question of true antigenic variation among B. garinii strains.


Animal genetic manipulation--a utilitarian response.
I examine the process and outcomes of animal genetic manipulation ('transgenesis') with reference to its morally salient features. I consider several objections to transgenesis. I examine and reject the alleged intrinsic wrongness of 'deliberate genetic sequence alteration,' as I do the notion that transgenesis may lead to human genetic manipulation. I examine the alleged wrongness of killing inherent in transgenesis, and suggest that the concept of 'replaceability' successfully justifies such killing, although not for entities deemed to possess 'personhood.' I examine 'significant suffering' associated with transgenesis and propose the radical conclusion that, although it would be wrong to prohibit animal genetic manipulation per se, utilitarians ought to support a 'default prohibition' on transgenic experiments that entail significant suffering.


Chiral selenide-catalyzed enantioselective synthesis of trifluoromethylthiolated 2,5-disubstituted oxazolines.
Chiral selenide-catalyzed enantioselective trifluoromethylthiolation of 1,1-disubstituted alkenes is disclosed. By this method, a variety of chiral trifluoromethylthiolated 2,5-disubstituted oxazolines were obtained in good yields with high enantioselectivities. This work not only provides a new pathway for the synthesis of chiral oxazolines, but also expands the library of chiral trifluoromethylthiolated molecules.


High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors.
The promoter region of the mouse CCAAT-Enhancer Binding Protein (C/EBP alpha) gene is capable of directing high levels of expression of reporter constructs in various cell lines, albeit even in cells that do not express their endogenous C/EBP alpha gene. To understand the molecular mechanisms underlying this ubiquitous expression, we have characterized the promoter region of the mouse C/EBP alpha gene by a variety of in vitro and in vivo methods. We show that three sites related in sequence to USF, BTE and C/EBP binding sites and present in promoter region -350/+3, are recognized by proteins from rat liver nuclear extracts. The sequence of the C/EBP alpha promoter that includes the USF binding site is also capable of forming stable complexes with purified Myc+Max heterodimers and mutation of this site drastically reduces transcription of C/EBP alpha promoter luciferase constructs both in liver and non liver cell lines. In addition, we identify three novel protein-binding sites two of which display similarity to NF-1 and a NF kappa B binding sites. The region located between nucleotides -197 and -178 forms several heat-stable complexes with liver nuclear proteins in vitro which are recognized mainly by antibodies specific for C/EBP alpha. Furthermore, transient expression of C/EBP alpha and to a lesser extent C/EBP beta expression vectors, results in transactivation of a cotransfected C/EBP alpha promoter-luciferase reporter construct. These experiments support the notion that the C/EBP alpha gene is regulated by C/EBP alpha but other C/EBP-related proteins may also be involved.


The Effect of Nutrition Intervention with Oral Nutritional Supplements on Pancreatic and Bile Duct Cancer Patients Undergoing Chemotherapy.
Chemotherapy may negatively affect nutritional status and quality of life (QOL) in pancreatic cancer patients. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on pancreatic and bile duct cancer patients undergoing chemotherapy. Among patients with progressive pancreatic and bile duct cancer receiving chemotherapy, the ONS group (n = 15) received two packs of ONS daily for 8 weeks while the non-ONS group (n = 19) did not. Anthropometric measures, dietary intake, nutritional status, and quality of life were assessed. ONS significantly increased daily intakes of energy, carbohydrates, proteins, and lipids at 8 weeks compared to the baseline. After 8 weeks, fat mass significantly increased in the ONS group. For patients in their first cycle of chemotherapy, body weight, fat-free mass, skeletal muscle mass, body cell mass, and fat mass increased in the ONS group but decreased in the non-ONS group. Fat mass increased in second or higher cycle only in the ONS group. Patient-generated subjective global assessments (PG-SGA) and fatigue scores in the Quality of Life Questionnaire Core 30 (QLQ-C30) improved in the ONS group. ONS might improve nutritional status by increasing fat mass and/or maintaining the body composition of pancreatic and bile duct cancer patients with chemotherapy, especially those in the first cycle, and alleviate fatigue symptoms.


Ecosystem approaches and health in Latin America.
Important environmental changes that have become increasingly pronounced in the last two centuries and that are seriously affecting human health require the development of integrated and participatory scientific approaches that can result in proposals for institutional and public policy changes. The purpose of this article is to offer some elements that can contribute to a line of reflection based on studies with ecosystem approaches in the Latin America context. The authors begin with a brief description of current scientific literature in public health that links ecosystems and human health in Latin America; next, they describe and compare the two prevailing trends that form the basis for the theoretical and methodological debates on ecosystem approaches; they also review the empirical research in Latin America or concerning Latin American countries in which an ecosystem approach has been adopted. The results point to limited scientific output on the interface between ecosystems and human health; aspects involving public participation and implementation of institutional changes and public policies are still in a rather incipient stage.


Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh.
Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE) activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 +/- 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low (< 129 microg/L), medium (130-264 microg/L) and high (> 265 microg/L). Study subjects were further sub-divided into two groups (<or=50 microg/L and > 50 microg/L) based on the recommended upper limit of water arsenic concentration (50 microg/L) in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PChE activity was assayed by spectrophotometer. Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 microg/L group compared to the <or=50 microg/L group. Moreover, PChE activity was significantly decreased in the skin (+) symptoms group compared to those without (-). We found a significant inverse relationship between arsenic exposure and PChE activity in a human population in Bangladesh. This research demonstrates a novel exposure-response relationship between arsenic and PChE activity which may explain one of the biological mechanisms through which arsenic exerts its neuro-and hepatotoxicity in humans.


Structural simplification of bioactive natural products with multicomponent synthesis. 3. Fused uracil-containing heterocycles as novel topoisomerase-targeting agents.
After the initial discovery of antiproliferative and apoptosis-inducing properties of a camptothecin-inspired pentacycle based on a 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine scaffold, a library of its analogues as well as their oxidized planar counterparts were prepared utilizing a practical multicomponent synthetic protocol. The synthesized compounds exhibited submicromolar to low micromolar antiproliferative potencies toward a panel of human cancer cell lines. Biochemical experiments are consistent with the dihydropyridine library members undergoing intracellular oxidation to the corresponding planar pyridines, which then inhibit topoisomerase II activity, leading to inhibition of proliferation and cell death. Because of facile synthetic preparation and promising antitopoisomerase activity, both the dihydropyridine and planar pyridine-based compounds represent a convenient starting point for anticancer drug discovery.


The uncomfortable reality … We simply do not know if general anesthesia negatively impacts the neurocognitive development of our small children.
Annually in the United States more than one million children under the age of 5 years are exposed to anesthetics for therapeutic and diagnostic procedures. Pre-clinical data in animal models has consistently shown that anesthetic exposure to the developing brain results in long-term cognitive deficits. Current clinical data addressing the safety of these pharmaceutical agents on the developing human brain is limited. Recently, there has been an enormous amount of attention directed at this potential public health issue in both pre-clinical investigations and ongoing human research. A number of these studies should add to our understanding about the impact anesthetic exposure will have on the developing human brain. Until then, there is little data that absolutely reassures clinicians and parents that the pharmaceutical agents used are indeed safe for our children. The uncomfortable reality is that despite the fact that there are more than one million children younger than 5 years old who receive general anesthesia in the United States annually, and thousands more who are deeply sedated for imaging and diagnostic studies or as a necessary adjunct to care in the intensive care unit, there is little data that assures clinicians and parents that the pharmaceutical agents used are indeed safe for the developing brain. That said, there are no convincing human data to suggest that they are not.


Peak Finder Metaserver - a novel application for finding peaks in ChIP-seq data.
Finding peaks in ChIP-seq is an important process in biological inference. In some cases, such as positioning nucleosomes with specific histone modifications or finding transcription factor binding specificities, the precision of the detected peak plays a significant role. There are several applications for finding peaks (called peak finders) based on different algorithms (e.g. MACS, Erange and HPeak). Benchmark studies have shown that the existing peak finders identify different peaks for the same dataset and it is not known which one is the most accurate. We present the first meta-server called Peak Finder MetaServer (PFMS) that collects results from several peak finders and produces consensus peaks. Our application accepts three standard ChIP-seq data formats: BED, BAM, and SAM. Sensitivity and specificity of seven widely used peak finders were examined. For the experiments we used three previously studied Transcription Factors (TF) ChIP-seq datasets and identified three of the selected peak finders that returned results with high specificity and very good sensitivity compared to the remaining four. We also ran PFMS using the three selected peak finders on the same TF datasets and achieved higher specificity and sensitivity than the peak finders individually. We show that combining outputs from up to seven peak finders yields better results than individual peak finders. In addition, three of the seven peak finders outperform the remaining four, and running PFMS with these three returns even more accurate results. Another added value of PFMS is a separate report of the peaks returned by each of the included peak finders.


Bed wise cost analysis of in-patient treatment of brachial plexus injury at a Level I trauma Center in India.
The aim was to calculate, in monetary terms, total cost incurred by a Level I trauma center in providing in-patient care to brachial plexus injury patients during their preoperative and the postoperative stay. All patients of brachial plexus injury admitted and discharged between January and December 2010 were included in the study. Total cost per bed was calculated under several cost heads in pre- and post-operative ward care. Intra-operative costs were excluded. A total of 69 patients were admitted in the year 2010. Of these 60 were operated and the rest were planned conservative management. The total cost incurred by the trauma center in providing in-patient care to patients admitted in the ward, excluding high dependency unit, came out to be Rs. 3,650.00/patient/bed/day. Of this Rs. 2,234.645, the maximum amount was incurred in providing manpower alone. The average preoperative wait was 12 days (maximum 41 days and minimum 1-day). The average postoperative stay was 2 days. Total cost incurred in the preoperative period was Rs. 2,975,125 (US$ 59392) or Rs. 43,117/patient (US$ 861). It was Rs. 386,948 (US$ 7724) in the postoperative period (Rs. 6,449 or US$ 129/patient). Nine patients were not operated and had waited from 2 to 12 days before finally being planned for observant treatment. This itself cost the hospital Rs. 226,328 (US$ 4518). By just reducing the preoperative length of stay to 1-day the cost can be brought down by 93% for brachial plexus injury patients alone and the beds can be used to admit more critical patients.


Prospective comparison of outcomes of percutaneous nephrolithotomy in elderly patients versus younger patients.
The purpose of the study was to prospectively compare operative and postoperative characteristics and outcomes in elderly patients undergoing percutaneous nephrolithotomy (PCNL) compared with younger patients. Prospectively collected data from the Clinical Research Office of the Endourological Society (CROES) Global PCNL Study database were used. Elderly patients were defined as those aged 70 years and above, while younger patients were those between 18 and 70 years of age. Matched and unmatched group comparisons were performed based on imaging modality used for assessing stone-free status. Patient characteristics, operative data, and postoperative outcomes were compared. The median age of the elderly group vs the young group was 74 years (range 70-93 years) vs 49 years. In the unmatched analysis, staghorn stones were seen at higher rates in the elderly group (27.8% vs 21.8%, P=0.014); however, the mean stone size was not significantly different (465.0 vs 422.8, P=0.063). The length of hospitalization was significantly longer in the elderly group compared with the young group in the unmatched analysis (5 days vs 4.1 days, P<0.001). The same difference was not apparent in the matched analysis (5.0 days vs 4.4 days, P=0.288). Overall complication rates were not significantly different in the unmatched analysis. In the matched analysis, however, a statistically significant higher rate of overall complications was seen. Stone-free rates were similar among all groups. PCNL in elderly patients over the age of 70 years produces results comparable to those seen in younger patients. With only a slightly higher-be it statistically significant-complication rate, the stone-free rate in older patients was the same as in the younger group.


Three-dimensional spatial cognition in a benthic fish, Corydoras aeneus.
The way animals move through space is likely to affect the way they learn and remember spatial information. For example, a pelagic fish, Astyanax fasciatus, moves freely in vertical and horizontal space and encodes information from both dimensions with similar accuracy. Benthic fish can also move with six degrees of freedom, but spend much of their time travelling over the substrate; hence they might be expected to prioritise the horizontal dimension. To understand how benthic fish encode and deploy three-dimensional spatial information we used a fully rotational Y-maze to test whether Corydoras aeneus (i) encode space as an integrated three-dimensional unit or as separate elements, by testing whether they can decompose a three-dimensional trajectory into its vertical and horizontal components, and (ii) whether they prioritise vertical or horizontal information when the two conflict. In contradiction to the expectation generated by our hypothesis, our results suggest that C. aeneus are better at extracting vertical information than horizontal information from a three-dimensional trajectory, suggesting that the vertical axis is learned and remembered robustly. Our results also showed that C. aeneus prioritise vertical information when it conflicts with horizontal information. From these results, we infer that benthic fish attend preferentially to a cue unique to the vertical axis, and we suggest that this cue is hydrostatic pressure.


Diabetes and the vitamin d connection.
Vitamin D deficiency, which is common in children and adults, causes rickets, osteomalacia, and osteoporosis. Most organs and immune cells have a vitamin D receptor, and some also have the capacity to metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. 1,25-Dihydroxyvitamin D is a potent immunomodulator that also enhances the production and secretion of several hormones, including insulin. Vitamin D deficiency has been associated with increased risk of type 1 diabetes. Glycemic control and insulin resistance are improved when vitamin D deficiency is corrected and calcium supplementation is adequate. 25-Hydroxyvitamin D (measure of vitamin D status) of less than 20 ng/mL is vitamin D deficiency and 21 to 29 ng/mL is insufficiency. Children and adults need at least 1000 IU of vitamin D per day to prevent deficiency when there is inadequate sun exposure.


Cytokinins secreted by Agrobacterium promote transformation by repressing a plant myb transcription factor.
Agrobacterium-mediated transformation is the most widely used technique for generating transgenic plants. However, many crops remain recalcitrant. We found that an Arabidopsis myb family transcription factor (MTF1) inhibited plant transformation susceptibility. Mutating MTF1 increased attachment of several Agrobacterium strains to roots and increased both stable and transient transformation in both susceptible and transformation-resistant Arabidopsis ecotypes. Cytokinins from Agrobacterium tumefaciens decreased the expression of MTF1 through activation of the cytokinin response regulator ARR3. Mutating AHK3 and AHK4, genes that encode cytokinin-responsive kinases, increased the expression of MTF1 and impaired plant transformation. Mutant mtf1 plants also had increased expression of AT14A, which encodes a putative transmembrane receptor for cell adhesion molecules. Plants overexpressing AT14A exhibited increased susceptibility to transformation, whereas at14a mutant plants exhibited decreased attachment of bacteria to roots and decreased transformation, suggesting that AT14A may serve as an anchor point for Agrobacteria. Thus, by promoting bacterial attachment and transformation of resistant plants and increasing such processes in susceptible plants, treating roots with cytokinins may help engineer crops with improved features or yield.


Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy.
Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the bony containment, mostly located intracortically in the proximal radius. The diagnosis of a periosteal ABC was confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy. Function conserving surgery could be performed, enabling reconstruction of the affected bone. Inhibition of RANKL with denosumab may offer therapeutic option for patients not only with giant cell tumors but also with ABCs.


Assessing technician effects when extracting quantities from microscope images.
Consider an experiment where the response is based on an image; e.g., an image captured to a computer file by a digital camera mounted on a microscope. Suppose relevant quantitative measures are extracted from the images so that results can be analyzed by conventional statistical methods. The steps involved in extracting the measures may require that the technicians, who are processing the images, perform some subjective manipulations. In this case, it is important to determine the bias and variability, if any, attributable to the technicians' decisions. This paper describes the experimental design and statistical analyses that are useful for those determinations. The design and analysis are illustrated by application to two biofilm research projects that involved quantitative image analysis. In one investigation, the technician was required to choose a threshold level, then the image analysis program automatically extracted relevant measures from the resulting black and white image. In the other investigation, the technician was required to choose fiducial points in each of two images collected on different microscopes; then the image analysis program registered the images by stretching, rotating, and overlaying them, so that their quantitative features could be correlated. These investigations elucidated the effects of the technicians' decisions, thereby helping us to assess properly the statistical uncertainties in the conclusions for the primary experiments.


A new threat to bees? Entomopathogenic nematodes used in biological pest control cause rapid mortality in Bombus terrestris.
There is currently a great deal of concern about population declines in pollinating insects. Many potential threats have been identified which may adversely affect the behaviour and health of both honey bees and bumble bees: these include pesticide exposure, and parasites and pathogens. Whether biological pest control agents adversely affect bees has been much less well studied: it is generally assumed that biological agents are safer for wildlife than chemical pesticides. The aim of this study was to test whether entomopathogenic nematodes sold as biological pest control products could potentially have adverse effects on the bumble bee Bombus terrestris. One product was a broad spectrum pest control agent containing both Heterorhabditis sp. and Steinernema sp., the other product was specifically for weevil control and contained only Steinernema kraussei. Both nematode products caused ≥80% mortality within the 96 h test period when bees were exposed to soil containing entomopathogenic nematodes at the recommended field concentration of 50 nematodes per cm(2) soil. Of particular concern is the fact that nematodes from the broad spectrum product could proliferate in the carcasses of dead bees, and therefore potentially infect a whole bee colony or spread to the wider environment.


Handling Motion-Blur in 3D Tracking and Rendering for Augmented Reality.
The contribution of this paper is two-fold. First, we show how to extend the ESM algorithm to handle motion blur in 3D object tracking. ESM is a powerful algorithm for template matching-based tracking, but it can fail under motion blur. We introduce an image formation model that explicitly consider the possibility of blur, and shows its results in a generalization of the original ESM algorithm. This allows to converge faster, more accurately and more robustly even under large amount of blur. Our second contribution is an efficient method for rendering the virtual objects under the estimated motion blur. It renders two images of the object under 3D perspective, and warps them to create many intermediate images. By fusing these images we obtain a final image for the virtual objects blurred consistently with the captured image. Because warping is much faster than 3D rendering, we can create realistically blurred images at a very low computational cost.


Global challenges in liver disease.
Immigration, cheap air travel, and globalization are all factors contributing to a worldwide spread of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. End-stage chronic liver disease (ESLD) as a result of co-infection with HBV/HCV is now the major cause of death for individuals who have been infected with the HIV virus. The high incidence of HCV infection in Egypt--the legacy left from the mass use of tartar emetic to eradicate schistosomiasis, as in other high prevalence areas--will take years to reduce. Steatohepatitis due to non-alcoholic fatty liver disease is developing into a new and major health problem as a result of rising levels of obesity in populations worldwide. Hepatic steatosis also has an adverse influence on the progression of other liver diseases including chronic HCV infection and alcoholic liver disease. In many countries, considerable public concern is on the rise due to increased levels of alcohol consumption adversely affecting younger and affluent age groups. With the rising prevalence of cirrhosis, primary hepatocellular carcinoma (HCC) is increasing in frequency as is that of primary intrahepatic cholangiocarcinoma. Finally, despite the successes of liver transplantation, many deserving patients are not getting transplants due to low levels of cadaver organ donation in many countries, thereby increasing pressures on the use of living donor liver transplantation. Only through a concerted effort from governments, health agencies, healthcare professionals at all levels, and the pharmaceutical industry can this grim outlook for liver disease worldwide be reversed.


Two myeloid leukemia cases with rare FLT3 fusions.
Genetic rearrangements involving FLT3 are rare and only recently have been detected in myeloid/lymphoid neoplasms associated with eosinophilia (MLN-eos) and chronic myeloproliferative disorders. Here we report two cases with FLT3 fusions in patients demonstrating mixed features of myelodysplastic/myeloproliferative neoplasms. In the first case, FLT3 was fused with a new fusion partner MYO18A in a patient with marrow features most consistent with atypical chronic myeloid leukemia; the second case involving ETV6-FLT3 fusion was observed in a case with bone marrow features most consistent with chronic myelomonocytic leukemia. Notably, we observed that samples from both patients demonstrated FLT3 inhibitor (quizartinib and sorafenib) sensitivity in ex vivo drug screening assay.


Effect of hormone secretory syndromes on neuroendocrine tumor prognosis.
The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: proton-pump inhibitors decrease acid secretion caused by gastrinomas. Somatostatin analogs can inhibit the secretion of multiple hormones and these are now the cornerstone for treating patients with a gastroenteropancreatic NET. However, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs and everolimus can also decrease symptoms of hypersecretion and increase progression-free survival. Several factors affect the survival in patients with a functioning NET. Complications of hypersecretion negatively impact survival; however, secretion of hormones is also often a sign of a well-differentiated NET and due to the symptoms, functioning NETs can be detected in an earlier stage suggesting a positive effect on prognosis. The effect on survival is also dependent on the type of hormone being secreted. This review aims to study the effect of hormone secretion on the prognosis of NETs with the contemporary treatments options available today.


Studying time to pregnancy by use of a retrospective design.
Biologic fertility can be measured using time to pregnancy (TTP). Retrospective designs, although lacking detailed timed information about behavior and exposure, are useful since they have a well-defined target population, often have good response rates, and are simpler and less expensive to conduct than prospective studies. This paper reviews retrospective TTP studies from a methodological viewpoint and shows how methodological problems can be avoided or minimized by appropriate study design, conduct, and analysis. Sensitivity analyses using data from four European retrospective TTP studies are presented to explore the issues. Although the identified biases tend to have small impacts, the effects are not systematic across studies, and sensitivity analyses are recommended routinely. Planning bias can be checked by comparing propensity to report contraceptive failures in different exposure groups. Medical intervention bias can be avoided by censoring and inclusion of unsuccessful pregnancy attempts. Truncation bias can be a serious problem if unrecognized, but it is avoidable with appropriate study design and/or analysis. Behavior change bias can be minimized by assessing the covariates at the beginning of unprotected intercourse. More complete inference is possible if the study design covers the whole population, not just those who achieve a pregnancy.


A comparative study of handsewn versus stapled gastrojejunal anastomosis in laparoscopic Roux-en-Y gastric bypass.
The two basic techniques available in which to perform the gastrojejunal (GJ) anastomosis during a laparoscopic Roux-en-Y gastric bypass (LRYGBP) are stapled and handsewn. Few outcomes differences have been noted between the two to recommend one as a superior approach. We present our findings in comparison of the two methods. This is a retrospective review of all patients who underwent LRYGBP at a single institution during a 3-year period. The two different techniques that were used were a linear stapled and handsewn anastomosis with an anastomotic diameter of 18 mm. The groups were compared for postoperative complications, including stricture, anastomotic leak, and the need for early reoperation. All patients were followed up for a minimum period of 8 months. A total of 222 patients were analyzed after excluding 4 patients: 3 for revisional surgery and 1 for conversion to open. There were 99 patients in the stapled group and 123 in the handsewn group. In both groups, patients were predominantly female. The average age was 42.63 in the stapled group and 44.33 in the handsewn group (P = 0.218). Body mass index was 48.23 in the stapled group and 47.91 in the handsewn group (P = 0.733). Stricture rate in the stapled group was 10.1% (10/99) and 4.1% (5/123) in the handsewn group (P = 0.076). Four patients from the stapled group (4.08%) and six from the handsewn group (4.88%) needed early reoperation. One patient in each group had a GJ anastomotic leak (0.9%). There were no deaths. The incidence of anastomotic stricture tends to be lower with a handsewn technique with lower operative time. No difference was appreciated in the anastomotic leak or reexploration rate with either technique.


Estrogen memory effect in human hepatocytes during repeated cell division without hormone.
Transient stimulation of target tissues by sex steroids can cause long-lasting changes that may facilitate or alter responses to subsequent hormonal treatment. How these altered characteristics are propagated during cell division in the absence of the stimulating hormone is unknown. The human hepatocarcinoma cell line HepG2 was used as a model to examine the effects of estrogen on the synthesis of serum apolipoproteins in vitro. Treatment with low concentrations of estrogen for 24 to 48 hours resulted in long-lasting alterations in the kinetics with which the cells responded to subsequent stimulation with estrogen. Manifestation of this memory effect was correlated quantitatively with the induction and propagation of a moderate-affinity, nuclear, estrogen-binding protein with the characteristics of a type II estrogen receptor. The data indicate that transient exposure of these cells to estrogen can induce changes in their response characteristics and composition of nuclear proteins that are inherited by daughter cells grown in the absence of hormone for more than ten generations.


Fluorescent monomers: "bricks" that make a molecularly imprinted polymer "bright".
Molecularly imprinted polymers (MIPs) are potent and established recognition phases in separation and enrichment applications. Because of their robustness, versatility and format adaptability, they also constitute very promising sensing phases, especially when the active sensing element is directly integrated into the MIP. Fluorescent MIPs incorporating fluorescent monomers are perhaps the best developed and most successful approach here. This article reviews the state of the art in this field, discussing the pros and cons of the use of fluorescent dye and probe derivatives as such monomers, the different molecular interaction forces for template complexation, signalling modes and a variety of related approaches that have been realized over the years, including Förster resonance energy transfer processes, covalent imprinting, postmodification attachment of fluorescent units and conjugated polymers as MIPs; other measurement schemes and sensing chemistries that use MIPs and fluorescence interrogation to solve analytical problems (fluorescent competitive assays, fluorescent analytes, etc.) are not covered here. Throughout the article, photophysical processes are discussed to facilitate understanding of the effects that can occur when one is planning for a fluorescence response to happen in a constrained polymer matrix. The article concludes with a concise assessment of the suitability of the different formats for sensor realization.


Fracture dislocations of the tarsometatarsal joints: end results correlated with pathology and treatment.
Seventy-two patients with 76 fracture-dislocations of the Lisfranc tarsometatarsal joint complex were evaluated. Fifty-eight (81%) were polytrauma patients and the remainder suffered isolated injuries. Sixty of the original 72 patients were available for long-term study. Eight of these had an amputation at or shortly after the original admission, leaving 52 patients with 55 Lisfranc injuries for analysis. The average length of follow-up was 4.2 years (range, 20 months to 11 years). According to the Painful Foot Center scoring system, 27 feet (49%) achieved an excellent or good result and 28 (51%), a fair or poor result. Direct crush injuries did poorly with only one of eight scoring good or excellent. Of the various treatment modalities, open reduction and internal fixation with Kirschner wires yielded the best results. The major determinant of unacceptable results was identified as the quality of the initial reduction. Tarsal instability and late degenerative joint disease caused most of the symptoms. Twenty-three of the 52 patients (44%) have had or should have further mid-foot surgery to improve function and comfort. Because our results were often poor, our present protocol includes closed or open reduction and Kirschner wire internal fixation. Displacement greater than 2 mm or a talometatarsal angle greater than 15 degrees on radiographs following a closed reduction mandates open reduction.


Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
The role of ss-catenin signaling in mesodermal lineage formation and differentiation has been elusive. To define the role of ss-catenin signaling in these processes, we used a Dermo1(Twist2)(Cre/+) line to target a floxed beta-catenin allele, throughout the embryonic mesenchyme. Strikingly, the Dermo1(Cre/+); beta-catenin(f/-) conditional Knock Out embryos largely phenocopy Pitx1(-/-)/Pitx2(-/-) double knockout embryos, suggesting that ss-catenin signaling in the mesenchyme depends mostly on the PITX family of transcription factors. We have dissected this relationship further in the developing lungs and find that mesenchymal deletion of beta-catenin differentially affects two major mesenchymal lineages. The amplification but not differentiation of Fgf10-expressing parabronchial smooth muscle progenitor cells is drastically reduced. In the angioblast-endothelial lineage, however, only differentiation into mature endothelial cells is impaired. Taken together these findings reveal a hierarchy of gene activity involving ss-catenin and PITX, as important regulators of mesenchymal cell proliferation and differentiation.