Clinical characteristics and outcomes in neonates with perinatal acute respiratory distress syndrome in China: A national, multicentre, cross-sectional study.
Neonatal acute respiratory distress syndrome (NARDS) was defined in 2017 and the epidemiological data remain unknown. Our objective was to explore aetiological factors, clinical characteristics and outcomes in patients with perinatal NARDS. A multicentre, prospective, cross-sectional study was performed in 58 tertiary neonatal intensive care units in China from Jan 1, 2018 to June 30, 2019. Neonates diagnosed with NARDS were included. Primary outcomes were aetiological factors, clinical characteristics and outcomes. Binary logistic regression and multivariate cox proportional regression were performed to identify independent predictors for bronchopulmonary dysplasia (BPD) and/or death or single death. This study was registered with ClinicalTrials.Gov, NCT03311165. Among 70,013 admitted neonates, the incidence of NARDS was 1.44% (1005). The cumulative incidences were 65.6%, 86.7%, 94.1% within one, two and three days after birth. The median gestational age and birth weight were 36.4 weeks and 2700 g. Three main aetiological triggers included pneumonia (58.1%), asphyxia (24.3%) and early-onset sepsis (EOS) (21.3%). BPD and/or death was observed in 213 (21.2%) infants, consisting 104 (10.3%) BPD and 126 (12.6%) deaths. The numbers of mild, moderate and severe NARDS were 537 (53.4%), 286 (28.4%) and 182 (18.2%). Two or more doses of surfactant was associated with increased mortality as compared with one or less doses of surfactant (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.20-3.10, P = 0.006). Similarity also appeared in the comparison between EOS and non-EOS triggers (OR 1.57, 95% CI 1.06-2.33, P = 0.023). NARDS incidence was 1.44% and the three main aetiologies were pneumonia, asphyxia and EOS. The cumulative incidences were 65.6%, 86.7%, and 94.1% within one, two and three days after birth. Our results suggested that two or more doses of surfactant increased mortality compared with one or less doses of surfactant. The National Clinical Research Center of China and Clinical Medical Study Program of Children's Hospital of Chongqing Medical University (NCRC-2019-GP-13) and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197).


Antibiotic-impregnated cement spacer as definitive management for osteomyelitis.
Osteomyelitis is a challenge for orthopaedic surgeons. There is a lack of scientific evidence to guide treatment. The purpose of this study was to report the clinical outcome of unplanned retention of antibiotic-impregnated cement spacer (ACS) in the management of osteomyelitis. Eight patients (7 with tibial infections and 1 with a calcaneal infection) with osteomyelitis received radical debridement and insertion of an ACS into the bone defect as the definitive management. The mean follow-up period was 2 years (6 months to 4 years). All of these patients had a cement spacer in place. No patient exhibited radiographic evidence of excessive bone loss. The patients reported no or occasional mild pain and exhibited complete weight-bearing abilities, with the exception of one patient who required a crutch because of a spinal cord injury. Signs of recurrence of the osteomyelitis were not noted in any of the patients, and no fractures occurred at last follow-up. Our study suggests that a proportion of patients with unplanned retention of ACS appear to function well without necessarily requiring further surgical intervention.


The neuropeptide PACAP alleviates T. gondii infection-induced neuroinflammation and neuronal impairment.
Cerebral infection with the protozoan Toxoplasma gondii (T. gondii) is responsible for inflammation of the central nervous system (CNS) contributing to subtle neuronal alterations. Albeit essential for brain parasite control, continuous microglia activation and recruitment of peripheral immune cells entail distinct neuronal impairment upon infection-induced neuroinflammation. PACAP is an endogenous neuropeptide known to inhibit inflammation and promote neuronal survival. Since PACAP is actively transported into the CNS, we aimed to assess the impact of PACAP on the T. gondii-induced neuroinflammation and subsequent effects on neuronal homeostasis. Exogenous PACAP was administered intraperitoneally in the chronic stage of T. gondii infection, and brains were isolated for histopathological analysis and determination of pathogen levels. Immune cells from the brain, blood, and spleen were analyzed by flow cytometry, and the further production of inflammatory mediators was investigated by intracellular protein staining as well as expression levels by RT-qPCR. Neuronal and synaptic alterations were assessed on the transcriptional and protein level, focusing on neurotrophins, neurotrophin-receptors and signature synaptic markers. Here, we reveal that PACAP administration reduced the inflammatory foci and the number of apoptotic cells in the brain parenchyma and restrained the activation of microglia and recruitment of monocytes. The neuropeptide reduced the expression of inflammatory mediators such as IFN-γ, IL-6, iNOS, and IL-1β. Moreover, PACAP diminished IFN-γ production by recruited CD4+ T cells in the CNS. Importantly, PACAP promoted neuronal health via increased expression of the neurotrophin BDNF and reduction of p75NTR, a receptor related to neuronal cell death. In addition, PACAP administration was associated with increased expression of transporters involved in glutamatergic and GABAergic signaling that are particularly affected during cerebral toxoplasmosis. Together, our findings unravel the beneficial effects of exogenous PACAP treatment upon infection-induced neuroinflammation, highlighting the potential implication of neuropeptides to promote neuronal survival and minimize synaptic prejudice.


MRI in otology: applications in cholesteatoma and Ménière's disease.
Imaging of middle-ear cholesteatoma with diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI), and inner-ear endolymphatic hydrops (in Ménière's disease) with post-gadolinium high-resolution MRI, are reviewed. DWI MRI provides for a more specific diagnosis of tympano-mastoid cholesteatoma. There is an established and increasing role of DWI MRI in detecting both primary and postoperative cholesteatoma, localising disease, and planning surgery. The contemporary diagnostic accuracy of DWI is reviewed, pitfalls in interpretation are described, and potential future developments are highlighted. High-resolution post-gadolinium MRI of the inner ear is being explored for diagnosing endolymphatic hydrops. There is now increasing data to validate the application of three-dimensional (3D)-fluid attenuated inversion recovery (FLAIR) sequences, performed at 4 hours post-intravenous gadolinium, in the setting of potential Ménière's disease. The clinical context and the evolution of these MRI techniques are discussed. Current MRI-based grading schemes for endolymphatic hydrops are described, together with the available data on their clinical implications.


Evaluating Newborns at Risk for Early-Onset Sepsis.
Early-onset sepsis (EOS) is an important cause of neonatal morbidity. Despite extensive study, identifying at-risk newborns remains challenging, especially if they are initially well appearing. Existing official EOS recommendations suggest a conservative approach that likely results in overtreatment of a low-risk population. Recent studies indicate that more precise risk assessment and alternative management strategies could decrease the number of infants exposed to blood draws and antibiotics during evaluations for EOS. This article reviews existing guidelines and provides an overview of the Bayesian sepsis calculator and serial observation as an alternative to laboratory studies and empirical antibiotics.


Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo (Bubalus bubalis).
Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months (n = 24, less than 24 months; n = 26, greater than 24 months) were randomly assigned to groups subject to either natural daylight +4 h supplemental light (n = 25) or natural day light (n = 25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were greater than 27 degrees C and less than 70% during the daytime, respectively. Light-supplemented heifers had 16.2 kg net body weight (BW) gain at 9 weeks compared to 20.8 kg for controls, but higher mean Prl after 6.5 weeks (P less than 0.01), and higher P4 (0.41 vs 0.19 ng/ml; P less than 0.06) than control heifers. Older heifers had 39.7% greater BW (P less than 0.01), but a net 4.3% BW gain compared to a 10.1% gain for younger heifers at 10 weeks. Older, light-supplemented heifers had higher mean P4 (0.63 vs 0.19 ng/ml; P less than 0.07) than the other groups. These weight and hormonal changes suggest that 4 h supplemental light can alter growth and endocrine function in buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body weight during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.


LINC01436 Inhibited miR-585-3p Expression and Upregulated MAPK1 Expression to Promote Gastric Cancer Progression.
Gastric cancer (GC) is a prevalent type of digestion system malignancies. Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be prognostic factors and biological regulators in human cancers. The current study aimed to explore the role of long intergenic non-protein coding RNA 1436 (LINC01436) and its underlying mechanism in the progression of GC. RT-qPCR was conducted to measure RNA expression. Western blot was used for exploration of protein level. CCK-8, caspase-3 activity, and transwell assays were applied to evaluate the proliferative, apoptotic, and migratory abilities of GC cells, respectively. Mechanical experiments were used to probe the molecular interplay between genes. High LINC01436 level suggested low overall survival in GC patients, and LINC01436 was highly expressed in GC tissues and cells. Besides, LINC01436 knockdown hampered cell proliferation and migration, while facilitated cell apoptosis. Mechanistically, LINC01436 upregulated mitogen-activated protein kinase 1 (MAPK1) expression by competitively binding with miR-585-3p and inhibiting miR-585-3p expression. Furthermore, LINC01436 negatively regulated miR-585-3p expression by enhancing the zeste 2 polycomb repressive complex 2 subunit (EZH2)-induced trimethylation of histone H3 at lysine 27 (H3K27me3) on miR-585-3p promoter. Final rescue assays revealed that overexpression of MAPK1 could rescue the suppressive influence of LINC01436 depletion on GC progression. LINC01436 epigenetically silences miR-585-3p and acts as miR-585-3p to upregulate MAPK1 expression and promote GC progression.


Microbiological criteria for Campylobacter in broiler carcasses in Italy: a possible approach to derive them.
The aim of this paper was to provide suitable microbiological criteria (MC) for Campylobacter in broiler carcasses and a sampling plan to verify compliance with such criteria. Data were gathered in the presence and concentration of Campylobacter in broiler carcasses collected in three different Italian slaughterhouses, labelled as A, B and C. The sampling plan to be validated in each slaughterhouse included the analysis of three different carcasses collected immediately after chilling from 30 different lots, for a total of 90 samples per slaughterhouse. The number of positive samples containing above 100 CFU/g and above 1,000 CFU/g throughout the 30 tested lots was determined to estimate between-lot variability. Based on this information, the performance of four MC was evaluated for lot compliance: i) n=3; c=0; m=100 CFU/g; ii) n=3; c=0; m=1,000 CFU/g; iii) n=3; c=1; m=1,000 CFU/g and iv) n=3; c=2; m=1,000 CFU/g. Positive Campylobacter samples were found in 60% of the lots tested in slaughterhouses A and C and in 73.3% of lots from slaughterhouse B. The differences among the three slaughterhouses in the mean Campylobacter levels found in positive samples were not significant and were used to evaluate the performance of the MC. The level of lot compliance to different MC was calculated and for the most stringent one (n=3; c=0; m=100 CFU/g) was 40% at slaughterhouses A and C but only 26.7% at slaughterhouse B. The results of this study show an alternative approach to establish MC for Campylobacter in broilers. According to (1) Campylobacter prevalence and concentration in Italy, (2) applied experimental plan and (3) selected slaughterhouses, the number of compliant lots to the suggested MC ranged between 26.7 and 100%. The selection of the fit for purpose MC is a risk manager decision, based on a reasonable balance between public health and cost for poultry industries.


Opening wedge trapezial osteotomy as possible treatment for early trapeziometacarpal osteoarthritis: a biomechanical investigation of radial subluxation, contact area, and contact pressure.
Radial subluxation and cartilage thinning have been associated with initiation and accelerated development of osteoarthritis of the trapeziometacarpal joint. Few investigators have reported on the benefits of opening wedge trapezial osteotomy for altering the contact mechanics of the trapeziometacarpal joint as a possible deterrent to the initiation or progression of osteoarthritis. We used cadaveric specimens to determine whether opening wedge osteotomy of the trapezium was successful in reducing radial subluxation of the metacarpal base and to quantify the contact area and pressure on the trapezial surface during simulated lateral pinch. We used 8 fresh-frozen specimens in this study. The flexor pollicis longus, abductor pollicis longus, adductor pollicis, abductor pollicis brevis, and flexor pollicis brevis/opponens pollicis tendons were each loaded to simulate the thumb in lateral pinch position. We measured radial subluxation from anteroposterior radiographs before and after placement of a 15° wedge. We used real-time sensors to analyze contact pressure and contact area distribution on the trapezium. Center of force in the normal joint under lateral pinch loading was primarily located in the dorsal region of the trapezium. After wedge placement, contact pressure increased in the ulnar-dorsal region by 76%. Mean contact area increased in the ulnar-dorsal region from 0.05 to 0.07 cm(2), and in the ulnar-volar region from 0.003 to 0.024 cm(2). The average reduction in joint subluxation was 64%. The 15° opening wedge osteotomy of the trapezium reduced radial subluxation of the metacarpal on the trapezium and increased contact pressure and contact area away from the diseased compartments of the trapezial surface. Trapezial osteotomy addresses the 2 preeminent theories about the initiation and progression of osteoarthritis. By reducing radial subluxation and altering contact pressure and contact area, trapezial osteotomy may prove an alternative to first metacarpal extension osteotomy or ligament reconstruction in early stages of degenerative arthritis of the trapeziometacarpal joint.


Determinants of access to chronic illness care: a mixed-methods evaluation of a national multifaceted chronic disease package for Indigenous Australians.
Indigenous Australians have a disproportionately high burden of chronic illness, and relatively poor access to healthcare. This paper examines how a national multicomponent programme aimed at improving prevention and management of chronic disease among Australian Indigenous people addressed various dimensions of access. Data from a place-based, mixed-methods formative evaluation were analysed against a framework that defines supply and demand-side dimensions to access. The evaluation included 24 geographically bounded 'sentinel sites' that included a range of primary care service organisations. It drew on administrative data on service utilisation, focus group and interview data on community members' and service providers' perceptions of chronic illness care between 2010 and 2013. Urban, regional and remote areas of Australia that have relatively large Indigenous populations. 670 community members participated in focus groups; 374 practitioners and representatives of regional primary care support organisations participated in in-depth interviews. The programme largely addressed supply-side dimensions of access with less focus or impact on demand-side dimensions. Application of the access framework highlighted the complex inter-relationships between dimensions of access. Key ongoing challenges are achieving population coverage through a national programme, reaching high-need groups and ensuring provision of ongoing care. Strategies to improve access to chronic illness care for this population need to be tailored to local circumstances and address the range of dimensions of access on both the demand and supply sides. These findings highlight the importance of flexibility in national programme guidelines to support locally determined strategies.


A Neural Integrity Monitor Electromyography Endotracheal Tube Causes More Severe Postoperative Sore Throat Than a Standard Endotracheal Tube in Adults: A Prospective Cohort Study.
This study aimed at figuring out the different effects of a neural integrity monitor electromyography endotracheal tube (NIM-EMG-ETT) and a standard endotracheal tube (ETT) on postoperative sore throat (POST). This prospective cohort study enrolled 143 patients scheduled to undergo general anesthesia with endotracheal intubation. Patients were allocated into three groups: Group A, non-thyroid surgery with a standard ETT; Group B, thyroid surgery with a standard ETT; Group C, thyroid surgery with a NIM-EMG-ETT. The incidence, the severity and visual analog scale (VAS) of POST were recorded. The incidence and the severity of POST were tested by χ2 test or Fisher's exact test. And VAS of POST was tested by Kruskal-Wallis test. The incidences of POST in Group B and Group C were significantly higher than that of Group A at all the time points after extubation (P < 0.001). The incidences of POST in Group C was significantly higher than that in Group B at 8 h, 24 h and 48 h after extubation (89.4% vs. 68.8%, P = 0.014, relative risk (RR) 1.30, 95% confidence interval (CI) 1.05-1.61; 89.4% vs. 58.3%, P = 0.001, RR 1.53, 95% CI 1.18-1.98; 76.6% vs. 45.8%, P = 0.002, RR 1.67, 95% CI 1.18-2.36). Moreover, there was a significant higher VAS of POST and more serious POST with Group C than with Group B. A NIM-EMG-ETT may induce higher incidence of POST and more serious POST than a standard ETT. Chinese Clinical Trail Registry ( http://www.chictr.org.cn/index.aspx , ChiCTR2200058896, 2022-4-18).


Single-molecule enzymatic reaction dynamics and mechanisms of GPX3 and TRXh9 from Arabidopsis thaliana.
Glutathione peroxidases (GPXs) regulate the levels of reactive oxygen species in cells and tissues. During the redox cycling, the plant GPX is regenerated by thioredoxins (TRXs) as reductant rather than glutathione as the electron donor. However, the direct experimental observation on the interaction dynamics between GPXs and TRXs has not been reported, and the redox mechanism is unclear. In this work, the protein interactions between oxidized AtGPX3 and reduced AtTRXh9 have been studied using single-molecule fluorescence resonance energy transfer (smFRET). The obtained results indicate there are four processes in these two protein interaction, including biological recognition, binding, intermediate and unbinding state. Two enzymatic reaction intermediate states have been identified in the dissociation of AtGPX3-AtTRXh9 complex from binding to unbinding state, suggesting two types of interaction pathways and intermediate complexes. In particular, the dynamical study reveals that the redox reaction between oxidized AtGPX3 and reduced AtTRXh9 is realized through the forming and breaking of disulfide bonds via the active sites of Cys4 and Cys57 in AtTRXh9. These findings are of significant for deep understanding the redox reaction and mechanism between GPXs and TRXs enzymes, and studying other protein dynamics at single-molecule level.


Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in Parkinson disease.
Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity (n=42), bradykinesia (n=38), and gait speed (n=45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS.


Studies on exogenous and endogenous interaction of gastrin and secretin in a case of achalasia.
Studies were carried out in a case of achalasia. Administration of secretin caused relaxation of the spastic condition of LES, and high levels of serum gastrin and lower levels of plasma secretin are suggested to be related with the abnormally spastic condition of LES in the patient.


Robust brain MR image compressive sensing via re-weighted total variation and sparse regression.
Total variation (TV) and non-local self-similarity (NSS) are powerful tools for successfully enhancing compressive sensing performance. However, standard TV approaches often over-smooth detailed edges in the image, due to the uniform regularization of gradient magnitude. In this paper, a novel compressed sensing method for the reconstruction of medical images is proposed, the image edges are well preserved with the proposed reweighted TV. The redundancy of the NSS patch also is leveraged through the sparse regression model. The proposed model was solved with an efficient strategy of the Alternating Direction Method of Multipliers (ADMM) algorithm. Experimental results on thesimulated phantom, brain Magnetic resonance imaging (MRI) show that the proposed method outperforms the state-of-the-art compressed sensing approaches.


Technical note: age estimation by using pubic bone densitometry according to a twofold mode of CT measurement.
In forensic anthropology, age estimation is a major element in the determination of a biological profile and the identification of individuals. Thus, many anatomical structures have been studied, such as the pubic symphysis, which is a source of major interest due to its late maturation. One of the most well-known methods of assessment is the Suchey-Brooks (SB) system based on the morphological characteristics of the pubic symphysis. The aim of this study was to propose linear regression formulae in order to deduce chronological age from bone density, using both Hounsfield unit (HU), and mean bone density (mBD) values of the pubic symphysis. Moreover, we intended to test the reliability and then to explore the feasibility of using HU instead of mBD values for age estimation. We built retrospectively a reference sample of 400 pubic symphyses using computed tomography at a French hospital and a test sample of 120 pubic symphyses. Equations were created to establish linear regression models for age estimation. Inaccuracy and bias were calculated for individuals aged more or less than 40 years. We highlighted homogeneous mean absolute errors for both HU and mBD values, most of them being less than 10 years. Moreover, we reported a moderate overestimation for younger individuals and a very small underestimation for older individuals. This study proposes a correlation between the bone density and age of individuals with a valuable level of reliability. Finally, HU measurements seem to be suitable for linking bone density with the age of individuals in forensic practice.


Protein tyrosine phosphatase non-receptor Type 2 regulates IFN-γ-induced cytokine signaling in THP-1 monocytes.
We have previously shown that the Crohn's disease (CD)-associated gene protein tyrosine phosphatase non-receptor Type 2 (PTPN2) regulates interferon gamma (IFN-γ)-induced signaling and barrier function in intestinal epithelial cells. Overactivation of immature immune cells has been demonstrated in CD and elevated levels of proinflammatory cytokines, such as IFN-γ, play an important pathophysiological role in this disease. Here we studied the role of PTPN2 in the regulation of IFN-γ-induced signaling in THP-1 monocytic cells. Protein analysis was performed by Western blotting, PTPN2 knockdown was induced by siRNA, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). We demonstrated that IFN-γ (1000 U/mL) treatment of THP-1 cells elevates PTPN2 protein, reaching a peak by 24 hours. Increased PTPN2 expression, in turn, correlated with decreased activity of the signaling molecules, signal transducer and activator of transcription (STAT) 1 and STAT3. Loss of PTPN2 potentiated IFN-γ-induced phosphorylation of both of the STATs and of the mitogen-activated protein kinase (MAPK) family member, p38. However, PTPN2 loss did not affect the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase. As a functional consequence, PTPN2 knockdown elevated the IFN-γ-induced secretion of the proinflammatory cytokines interleukin-6 (IL-6) and macrophage chemoattractant protein 1 (MCP-1). Our data demonstrate that IFN-γ enhances PTPN2 protein in THP-1 cells and loss of PTPN2 promotes IFN-γ-induced STAT signaling and secretion of IL-6 and MCP-1. Therefore, we show that PTPN2 regulates inflammation-related events and PTPN2 dysregulation may contribute to the onset as well as to the perpetuation of inflammatory events associated with CD.


[Bovine coronavirus reproduction in the continuous cell cultures at a temperature of 34 degrees C].
Cultivation of bovine coronavirus at 34 degrees C showed the relationship of the degree of its reproduction to the cellular system. The possibility of obtaining the double yield of bovine coronavirus was demonstrated in MDBK and Vero cell cultures at 34 degrees C.


Regulation of the cAMP signal transduction pathway by protein kinase C in rat submandibular cells.
Treatment of rat submandibular acinar cell extracts with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) caused the dose-dependent activation of protein kinase C (PKC), assessed by the phosphorylation of a novel and highly specific substrate. This effect was duplicated by a diacylglycerol, but not by the 4 alpha-phorbol ester 4 alpha-phorbol 12,13-didecanoate. The TPA elevation of PKC was blocked by the PKC inhibitors H-7 and sangivamycin. In intact cells, TPA caused the translocation of PKC from cytosol to membrane, consistent with its known mode of activation. The beta-adrenergic agonist, isoproterenol, stimulated cAMP levels which were significantly reduced by preactivation of PKC. This inhibitory PKC effect was reversed by H-7. When cAMP was stimulated at the post-receptor level, however, by forskolin, NaF or GTP[gamma S], PKC did not inhibit, but rather enhanced the cyclic nucleotide response. Since PKC phosphorylated an endogenous protein of 55 kDa, the size of the beta 1 receptor, these findings indicate that, as in other cell types, PKC can desensitize adenylate cyclase by direct phosphorylation of the beta receptor, but potentiate the cAMP response by a post-receptor mechanism. In mucin secretion studies in the model, TPA alone caused the cAMP-independent release of up to 44% total mucin, which was much less than additive with the isoproterenol response. When the cAMP-mucosecretory response was stimulated at the adenylate cyclase level by forskolin, however, the TPA + forskolin effects were additive. These findings on the modulation of cAMP by PKC indicate cross-talk regulation in the phosphoinositide-cAMP signal transduction pathways in submandibular acinar cells.


Termination of focal atrial tachycardia by adenosine triphosphate.
An atrial aneurysm gave rise to incessant atrial tachycardia in a 21 year old Seychellian soldier. This arrhythmia was suppressed by intravenous adenosine triphosphate and ajmaline. Resection of the aneurysm abolished the arrhythmia and re-established sinus rhythm.


Social transmission of bacterial symbionts homogenizes the microbiome within and across generations of group-living spiders.
Disentangling modes and fidelity of symbiont transmission are key for understanding host-symbiont associations in wild populations. In group-living animals, social transmission may evolve to ensure high-fidelity transmission of symbionts, since non-reproducing helpers constitute a dead-end for vertical transmission. We investigated symbiont transmission in the social spider Stegodyphus dumicola, which lives in family groups where the majority of females are non-reproducing helpers, females feed offspring by regurgitation, and individuals feed communally on insect prey. Group members share temporally stable microbiomes across generations, while distinct variation in microbiome composition exists between groups. We hypothesized that horizontal transmission of symbionts is enhanced by social interactions, and investigated transmission routes within (horizontal) and across (vertical) generations using bacterial 16S rRNA gene amplicon sequencing in three experiments: (i) individuals were sampled at all life stages to assess at which life stage the microbiome is acquired. (ii) a cross-fostering design was employed to test whether offspring carry the microbiome from their natal nest, or acquire the microbiome of the foster nest via social transmission. (iii) adult spiders with different microbiome compositions were mixed to assess whether social transmission homogenizes microbiome composition among group members. We demonstrate that offspring hatch symbiont-free, and bacterial symbionts are transmitted vertically across generations by social interactions with the onset of regurgitation feeding by (foster)mothers in an early life stage. Social transmission governs horizontal inter-individual mixing and homogenization of microbiome composition among nest mates. We conclude that temporally stable host-symbiont associations in social species can be facilitated and maintained by high-fidelity social transmission.


Higher cortical thickness/volume in Alzheimer's-related regions: protective factor or risk factor?
Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes.


Effects of high exposure concentrations of inhaled low-toxicity dust on pulmonary function in guinea pigs.
The acute pulmonary function response to graded levels of a low toxicity dust was studied in guinea pigs. Four groups of five male guinea pigs each were exposed to mean concentrations of 0, 0.25, 1.01 and 5.39 mg Foundry Hill Clay l-1 air with mass median aerodynamic diameters of 2.6, 4.6 and 6.7 microns, respectively. There was a 15-min pre-exposure period to clean air, a 1-h exposure to the test atmosphere and then a 1-h recovery period with exposure to clean air. Concentration-related changes, compared to the pre-exposure period, occurred with a rapid onset in a number of parameters. Generally, the severity of observed effects increased with exposure time and, therefore, with inhaled dose. Statistically significant changes (P < 0.05) were observed in tidal volume, dynamic compliance, dynamic resistance, flow, pressure and minute volume during the last 15 min of exposure. The observed changes were consistent with acute bronchoconstriction. These effects reversed rapidly and there were no significant changes 1 h post-exposure. These results suggest that adverse physiological responses of short duration can occur when animals are exposed via inhalation to low-toxicity materials in the concentration range 0.25-5 mg l-1.


Stereoselective aspects of the metabolic activation of benzo[a]pyrene by human skin in vitro.
Benzo[a]pyrene (BP) is activated within tissues in both a regio- and a stereoselective manner and, since human skin is sensitive to tumour induction by polycyclic aromatic hydrocarbons (PAH), the steroselective metabolism of BP in this tissue has been investigated. Samples of skin from eleven individuals were treated with [3H]BP in short-term organ culture. Two samples were also treated with mixtures of [14C](+)- and (-)-trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-dihydrodiol) in varying proportions. Following application of [3H] BP, more 7,8-dihydrodiol was recovered from the skin itself than from the culture fluid in ten cases; no 7.8-dihydrodiol was detected in extracts from the eleventh. The 7,8-dihydrodiol metabolite was extracted predominantly (range 74-greater than 99%) as the (-)-enantiomer in nine of these ten patients, although proportionately more (+)-enantiomer was recovered from the culture fluid than from the skin in each case. The relative proportions of [3H]BP tetrols derived from syn- and anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydroxybenzo[a]pyrene (BPDE) detected in these extracts was more variable. When skin samples were treated with [14C]BP-7,8-dihydrodiol, more anti- than syn-BPDE-derived tetrols were extracted, irrespective of the optical purity of the dihydrodiol applied. These findings provide evidence for interindividual variations in the stereoselective metabolism of BP, which may be of some importance in determining individual susceptibility to PAH-induced skin carcinogenesis.


Morphology of local "stridulation" interneurons in the metathoracic ganglion of the acridid grasshopper Omocestus viridulus L.
The morphological characteristics of five types of local spiking interneurons in the metathoracic ganglion of the acridid grasshopper Omocestus viridulus L. have been revealed by intracellular injection of the fluorescent dye Lucifer Yellow. All these neurons are active during induced stridulation and discharge in the stridulation rhythm. They are structurally unlike any of the metathoracic local interneurons previously described in the Acrididae. Type 1: Unilateral interneurons in the metathoracic neuromere; soma in anterior position; arborization dorsal, in anterolateral, posterolateral, and midline regions. Type 2: Unilateral interneurons in the metathoracic neuromere; neurite with characteristic hairpin bend; soma in lateral position; arborization through the lateral neuropil region. Type 3: Unilateral interneurons in the metathoracic and abdominal neuromeres; soma anterior at the base of the connective; arborization dorsal, in anterolateral, posterolateral, and midline regions, with ladderlike branches into the abdominal neuromeres. Type 4: Symmetrically bilateral neurons; soma in ventral median position; arborization dorsal, in anterolateral, posterolateral, and midline regions. Ipsilateral branches mostly smooth, contralateral mostly varicose. Type 5: Asymmetrically bilateral neurons, soma in ventral median position; ipsilateral branches mostly smooth, contralateral mostly varicose. The ipsilateral branches in particular penetrate all layers of the ganglion. The main arborizations of interneurons of types 1 and 4, and to some extent those of types 3 and 5, occupy the same region, which extends very far dorsally into the vicinity of the median and lateral tracts. There are additional antero- and posterolateral branches in the metathoracic neuromere, in positions where in principle they can overlap with the arborizations of the motoneurons. The interneurons of type 2, and to some extent type 5, arborize mainly in a lateral region that also includes deeper layers of the ganglion and hence encompasses the projections of mechanoreceptive proprioceptors. The interneurons of types 1, 3, and 4 have so-called "sister" neurons, identical to the typical neurons in their metathoracic arborizations but with additional collaterals that pass into the mesothoracic ganglion.


Effect of polar solvents on beta-carotene radical precursor.
Beta-carotene forms radicals in chloroform upon photo-excitation (i) in the femtosecond time-scale by direct electron ejection into chloroform and (ii) in the microsecond time-scale by secondary reactions with chloroform radicals formed in the faster reactions. The precursor for beta-carotene radical cation decays in a second-order reaction in the mixed solvents, with a rate decreasing for increasing dielectric constant of cosolvent (acetic acid < ethanol < acetonitrile approximately methanol). The precursor is assigned as an ion pair from which the beta-carotene radical cation is formed in neat chloroform, but in more polar solvents it reacts at least partly through disproportionation in a bimolecular reaction promoted by the presence of ions. The stabilization of the radical precursor by increased solvent polarity, allowing for deactivation of the precursor by an alternative reaction channel, is discussed in relation to the balance of pro- and antioxidative properties of beta-carotene at lipid/water interfaces.


APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica.
Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single-nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not in the APOA5 gene increase susceptibility to MI.


Node Oligorecurrence in Prostate Cancer: A Challenge.
Within the oligometastatic state, oligorecurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally, it is an emergent situation that we are facing more frequently mainly due to (a) the incorporation into clinical practice of the PSMA-PET that provides strikingly increased superior images in comparison to conventional imaging, with higher sensitivity and specificity; (b) the higher detection rates of bone and node disease with extremely low levels of PSA; and (c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improving the clinical outcome. In this work, we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging-guided SBRT for the treatment of nodal recurrence in prostate cancer.


Treatment of incomplete abortion and miscarriage with misoprostol.
A literature review was conducted to determine whether misoprostol is an effective treatment for incomplete abortion and, if so, to recommend an appropriate regimen. All English language articles published before October 2007 using misoprostol in at least one of the study arms were reviewed to determine the efficacy of misoprostol when used to treat incomplete abortion in the first trimester. All available unpublished data previously presented at international scientific meetings were also reviewed. Sufficient evidence was found in support of misoprostol as a safe and effective means of non-surgical uterine evacuation. A single dose of misoprostol 600 microg oral is recommended for treatment of incomplete abortion in women presenting with a uterine size equivalent to 12 weeks gestation.


Measurement of violence during in-patient treatment and association with psychopathology.
Four available instruments for the measurement of violence were compared. The association between psychopathological status at admission and violence during in-patient treatment was examined. In 199 consecutively admitted patients (143 with schizophrenia or schizoaffective disorder, 56 with non-psychotic disorders), the PANSS was recorded at the time of admission. Violent behaviour against self and others was assessed for the total period of in-patient treatment using the scales MOAS, SDAS, SOAS and VS. The sumscores of the scales correlated highly (r between 0.78 and 0.91), but the scales differed in sensibility and inter-rater reliability. There was a strong association between thought disorders and violent behaviour during in-patient treatment in psychotic patients (beta = 0.34; P<0.001). Although constructed to measure different aspects of violence, all investigated instruments correlated highly. The psychopathological status at admission is associated with violent behaviour during in-patient treatment.


DFT Study of Mechanism and Stereochemistry of Nickel-Catalyzed trans-Arylative Desymmetrizing Cyclization of Alkyne-Tethered Malononitriles.
Present here is a density functional theory (DFT) study of the mechanism and origin of enantioselectivity of Ni-catalyzed desymmetric cyclization of alkyne-tethered malononitriles and aryl boronic acids. The reaction starts from transmetalation and arylnickel addition, followed by trans to cis isomerization to give cis-alkenyl nickel species. The stereodetermining step is the CN insertion, which prefers a transition state with the bystander CN group staying away from the ligand to reduce steric repulsion, and gives the final (R)-product.


Foraging behavior of a Dipteran leaf miner on exploited and unexploited hosts.
The foraging behavior of females of the leaf miner, Agromyza frontella (Rondani), (Diptera: Agromyzidae) when encountering unexploited or exploited alfalfa plants was studied in large field cages and in laboratory bioassays. Females did not recognize any exploited leaflets before contacting them and did not distinguish between leaflets with an egg or first instar larva and unexploited leaflets, even after contact. Only one fly oviposited in leaflets which contained 80-120 nutrition holes, one late second or third instar larva or which were marked with an epideictic pheromone in field cages. In laboratory bioassays females oviposited less in leaflets containing a second or third instar larva or an empty larval mine than in unexploited ones. Females foraging on unexploited leaflets engaged in area-restricted search and 10 of 11 females remained on the test plant for the full 60 min of observation. However, females foraging on exploited plants were much more active, spent a greater proportion of their time searching for suitable hosts, had the highest rates of visitation to all above ground plant parts and emigrated to the cage walls before 60 min had elapsed. These quantitative measures of foraging behavior indicated that females ranked plants after landing on them in the following order: unexploited plants >plants marked with pheromone or with many nutrition holes >plants with late instar larvae. The order of host ranking by foragers was in general agreement with the suitability of the host plants for larval survival, development and reproduction, as estimated from previous laboratory studies.Females of A. frontella foraging on unexploited alfalfa plants fed and oviposited significantly more often in the upper apical leaflets than in the lower, older leaflets. However, the choice of feeding site by flies on exploited plants did not vary with leaflet position (age), indicating that females fed in order to sample leaflet quality and that females investigated lower (older) leaves after they discovered that the preferred upper leaves were occupied. These data suggest that high quality oviposition sites may be limiting for A. frontella females, which could explain why superparasitism of leaflets sometimes occurs in nature, even when unexploited sites are available.


Safety and Efficacy of the Moderate Sedation During Flexible Bronchoscopic Procedure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Moderate sedatives have been increasingly used to improve patient comfort during flexible bronchoscopy (FB). However, routine use of moderate sedation during FB is controversial because its efficacy and safety are not well established. This study aims to evaluate the efficacy and safety of moderate sedation during FB. A search was made of Medline, EMBASE, and the Cochrane Library to May 2014. Randomized controlled trials (RCTs) and quasi-RCTs were included. The main analysis was designed to examine the efficacy of moderate sedation during FB in sedation than no-sedation. The willingness to repeat FB was significantly more in sedation than no-sedation (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.11-4.73; P = 0.02; I2 = 22.5). The duration of FB was shorter in sedation group than no-sedation group (standardized mean difference [SMD] -0.21; 95% CI -0.38 to -0.03; P = 0.02; I2 = 78.3%). Event of hypoxia was not significantly different between sedation and no-sedation groups (OR 0.86; 95% CI 0.42-1.73; P = 0.67; I2 = 0%). The SpO2 during procedure was not different between sedation and no-sedation groups (SMD -0.14; 95% CI -0.37 to 0.08; P = 0.21; I2 = 49.9%). However, in subgroup analysis without supplemental oxygen, the SpO2 was significantly lower in sedation than no-sedation group (SMD -0.45; 95% CI -0.78 to -0.11; P = 0.01; I2 = 0.0%). According to this meta-analysis, moderate sedation in FB would be useful in patients who will require repeated bronchoscopies as well as safe in respiratory depression. To our knowledge, although the various sedative drugs are already used in the real field, this analysis was the first attempt to quantify objective results. We anticipate more definite and studies designed to elucidate standardized outcomes for moderate sedation in FB.


Subcellular localization and characterization of vasopressin binding sites in the ventral septal area, lateral septum, and hippocampus of the rat brain.
[Arg8]-Vasopressin (AVP) has been shown to exert characteristic central physiological actions in the ventral septal area of the rat brain. This study reports the characterization of receptors for AVP in synaptic plasma membranes prepared from the ventral septal area, the lateral septum, and the hippocampus. Binding of [3H]AVP was temperature and time dependent, linearly related to protein concentration, saturable, and specific. Scatchard plot analysis suggested the presence of a population of binding sites in the three brain areas with dissociation constants and maximal binding capacities, respectively, of 1.06 +/- 0.39 nM and 24.0 +/- 7.01 fmol/mg of protein (mean +/- SEM; n = 3 for the ventral septal area, 0.92 +/- 0.13 nM and 47.0 +/- 4.96 fmol/mg of protein (n = 3) for the lateral septum, and 0.91 +/- 0.14 nM and 25 +/- 5.02 fmol/mg of protein (n = 3) for the hippocampus. In all three brain regions, the rank order of potencies of several vasopressin analogs, unrelated peptides, and other compounds for competitive displacement of ligand indicated a receptor with properties resembling those of the V1-like receptor for AVP. These data document the presence of a high-affinity, V1-like vasopressin receptor in the rat ventral septal area for which the pharmacological properties are similar to those previously reported in physiological studies.


HITSZ_CDR: an end-to-end chemical and disease relation extraction system for BioCreative V.
In this article, an end-to-end system was proposed for the challenge task of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction in BioCreative V, where DNER includes disease mention recognition (DMR) and normalization (DN). Evaluation on the challenge corpus showed that our system achieved the highest F1-scores 86.93% on DMR, 84.11% on DN, 43.04% on CID relation extraction, respectively. The F1-score on DMR is higher than our previous one reported by the challenge organizers (86.76%), the highest F1-score of the challenge.Database URL: http://database.oxfordjournals.org/content/2016/baw077.


Gastrointestinal nematode infections in wild ruminants Rupicapra rupicapra and Dama dama: influence of density and cohabitation with domestic ruminants.
The distribution of gastrointestinal nematodes in different populations of wild ruminants has been studied with regard to density of the animals and the presence of domestic ruminants in the habitat. The degree of parasite overdispersion among the hosts has been examined in the hypothesis of a negative binomial model of distribution. The results show that the density has a greater weight than cohabitation with domestic ruminants, in destabilizing the host-parasite relationship.


Molecular basis of calcium channel blockade.
Calcium plays a central role in cellular regulation, where its major function is activation. In the sinoatrial node, the entry of positively charged calcium ions through calcium channels in the plasma membrane generates an inward (depolarizing) current that contributes to pacemaker activity, whereas calcium entry in the atrioventricular (AV) node provides the major depolarizing current during AV conduction. In the working myocardial cells of the atria and ventricles, calcium entry through plasma membrane channels triggers calcium release from intracellular stores in the sarcoplasmic reticulum, and so plays a central role in excitation-contraction coupling. Calcium also serves as an intracellular messenger that binds to members of a family of intracellular calcium-binding proteins that include troponin and calmodulin. In the heart, calcium binding to troponin initiates systole, and formation of the calcium-calmodulin complex in vascular smooth muscle initiates a cascade of reactions that leads to vasoconstriction. Calcium channel blockers, by inhibiting the opening of calcium channels, attenuate all of these reactions; in the heart, they slow the sinus pacemaker and AV conduction and depress myocardial contractility. In smooth muscle, these drugs are vasodilators. Different members of the diverse group of chemical structures that block calcium channels have different specificities for different channels, and so differ in their effects on the cardiovascular system.


The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty.
Opioid abuse and opioid overdose deaths have increased significantly over the past decade. Naloxone is a potentially life-saving medication that can reverse opioid-induced respiratory depression, though precipitated opioid withdrawal can pose acute risks to the patient and medical personnel. The optimal naloxone dose is unclear and few studies address this question. A convenience sample of commonly available references were queried for the recommended IV naloxone dose. When dosing recommendations were different for opioid-tolerant patients these were also recorded. Twenty-five references were located. 48% recommended a starting dose ≤ 0.05 mg while 36% recommend a dose ten-fold higher. More than half of medical toxicology and general medical sources recommended a low-dose strategy with a starting dose lower than 0.05 mg IV. There are variations in the recommended doses for naloxone with ranges spanning an order of magnitude. Further exploration is needed to determine the dose that balances reversal of respiratory depression with mitigation of withdrawal.


[Treatment of advanced maxillary sinus squamous carcinoma: an analysis of 92 cases].
There is no satisfactory treatment for advanced maxillary sinus squamous carcinoma. The treatment strategy is controversial. This study aimed to explore a rational treatment for advanced maxillary sinus squamous carcinoma. Clinical data of 92 patients with stage T3-T4 maxillary sinus squamous cell carcinoma, treated in Cancer Center of Sun Yat-sen University from Jan.1978 to Dec.2001, were reviewed. Of the 92 patients, 21 received radiotherapy alone, 8 received surgery alone, 63 received multimodality therapy (51 received surgery combined with radiotherapy, and 12 received chemoradiotherapy). The 3-and 5-year survival rates were significantly lower in radiotherapy group and surgery group than in multimodality therapy group (19.0% and 25.0% vs. 46.0%, P<0.05; 9.5% and 12.5% vs. 33.3%, P<0.05). In multimodality therapy group, the 3-and 5-year survival rates were 33.3% and 23.8% for the patients who received radiotherapy followed by surgery, 52.9% and 47.1% for the patients who received surgery follow by radiotherapy, 53.8% and 30.8% for the patients who received pre-and postoperative radiotherapy, and 50.0% and 33.3% for the patients who received chemoradiotherapy. There were no significant differences in survival rate between these four subgroups (P>0.05). The efficacy of multimodality therapy is better than that of single therapy strategy for advanced maxillary sinus squamous carcinoma. The best treatment pattern for advanced maxillary sinus squamous carcinoma needs further research.


Long-term follow-up of local rectal cancer surgery by transanal endoscopic microsurgery.
In 1997 we launched a prospective program of transanal endoscopic microsurgery (TEM) for the treatment of rectal cancer. Suitability for TEM was based on endorectal ultrasound results, classified as follows: (I) benign tumors; (II) adenocarcinomas uT0 and uT1 with uN0; (III) adenocarcinomas uT2- uN0, low histological grade with intention to cure; and (IV) advanced stage adenocarcinomas with palliative care Transanal endoscopic microsurgery was performed in 218 patients: 122 adenomas, and 96 adenocarcinomas: group II-72, group III-19, and group IV-5. Follow-up was >24 months (median 59 months) in 61 patients. Nine were lost to follow-up, and so 52 patients were studied: group II-38, group III-11, and group IV-3. The Kaplan-Meier probability of nonrecurrence of adenocarcinoma by group was 93% in tumors in situ (Tis) and T1; and 77.8% in T2. The Kaplan-Meier probability of survival by group was 100% in Tis and T1 and 82% in T2. Rates of recurrence and long-term survival in Tis and T1 adenocarcinomas treated with TEM are similar to those in previously published reports using conventional surgery. Further studies are required in T2 adenocarcinomas to determine a definitive strategy.


Is it safe to include octogenarians at the start of a video-assisted thoracic surgery lobectomy programme?
The study aimed to investigate the safety of including patients ≥ 80 years of age at the start of a video-assisted thoracic surgery major pulmonary resection (VMPR) programme. Patients were considered for VMPR if the computed tomography/positron emission tomography (CT/PET) was suggestive of T1-3, N0-1 and M0 lesion. Age was not a criterion for exclusion at the very start of the programme. Data were collected prospectively and comparison made between two groups, (A) <80 years of age and (B) ≥ 80 years, in terms of preoperative risk factors, oncological and functional data, operative results, postoperative complications and survival. Between April 2005 and January 2011, 200 consecutive patients were considered for VMPR. A total of 160 had non-small-cell lung cancer, of whom 136 were in group A, with a median age of 66.5 (range: 42.8-79.4 years) and 24 in group B with a median age of 82 (range: 80-85.5 years). In group B, 13 were men and 11 were women. Rate of conversion to thoracotomy was similar (3 (12.5%) in group B vs 17 (12.5%) in group A, p = 0.65), and so was the mean hospital stay (5.8 ± 3.3 days in group B vs 5.9 ± 4.6 days in group A, p = 0.899). Admission to intensive care unit and atrial fibrillation were significantly higher in octogenarians (six (25%) and six (25%) in group B vs eight (5.9%) and nine (6.6%) in group A, p = 0.008 and p = 0.012, respectively). There was significantly less mean days of air leak in octogenarians (0.06 ± 0.3 days in group B vs 2.8 ± 5.6 days in group A, p = 0.000). Otherwise, there were no age-related differences in relation to morbidity, mortality and the 3-year survival rate. Octogenarians undergoing VMPR have a higher incidence of atrial fibrillation and admission to the intensive care unit for cardiopulmonary support but otherwise are no different from younger age groups when it comes to rate of conversion to thoracotomy, hospital stay, morbidity and mortality. Age should not be an excuse to deny the elderly curative VATS resection. In our experience, accepting octogenarians early in the VMPR programme did not compromise the outcome results.


Tissue expression and source of circulating αKlotho.
αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast Growth Factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data. Based on current literature and tissue expression atlases, we propose a classification of tissues into high, intermediate and low/absent Klotho expression. The functional relevance of Klotho in organs with low expression levels remain uncertain and there is currently limited data on a role for membrane-bound Klotho outside the kidney. Finally, we review the evidence for the tissue source of soluble Klotho, and conclude that the kidney is likely to be the principal source of circulating Klotho in physiology.


Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma.
Acute glaucoma is a leading cause of irreversible blindness in East Asia. The mechanisms underlying retinal neuronal injury induced by a sudden rise in intraocular pressure (IOP) remain obscure. Here we demonstrate that the activation of CXCL10/CXCR3 axis, which mediates the recruitment and activation of inflammatory cells, has a critical role in a mouse model of acute glaucoma. The mRNA and protein expression levels of CXCL10 and CXCR3 were significantly increased after IOP-induced retinal ischemia. Blockade of the CXCR3 pathway by deleting CXCR3 gene significantly attenuated ischemic injury-induced upregulation of inflammatory molecules (interleukin-1β and E-selectin), inhibited the recruitment of microglia/monocyte to the superficial retina, reduced peroxynitrite formation, and prevented the loss of neurons within the ganglion cell layer. In contrast, intravitreal delivery of CXCL10 increased leukocyte recruitment and retinal cell apoptosis. Inhibition of endoplasmic reticulum (ER) stress with chemical chaperones partially blocked ischemic injury-induced CXCL10 upregulation, whereas induction of ER stress with tunicamycin enhanced CXCL10 expression in retina and primary retinal ganglion cells. Interestingly, deleting CXCR3 attenuated ER stress-induced retinal cell death. In conclusion, these results indicate that ER stress-medicated activation of CXCL10/CXCR3 pathway has an important role in retinal inflammation and neuronal injury after high IOP-induced ischemia.


Rapid determination of flavonoids and phenolic acids in grape juices and wines by RP-HPLC/DAD: Method validation and characterization of commercial products of the new Brazilian varieties of grape.
A method for rapid determination of phenolic compounds by reversed-phase high-performance liquid chromatography (RP-HPLC), using a new column of faster resolution was validated and used to characterize commercial products produced with new grape Brazilian varieties of Northeast of Brazil. The in vitro antioxidant activity was also measured. The method showed linearity (R>0.9995), good precision (CV%<2.78), recovery (91.8-105.1%) and limits of detection (0.04-0.85mgL-1) and quantification (0.04-1.41mgL-1) according to other methods previously published with the difference of a run time of only 25min. The results obtained in the characterization of the samples differed for juices and wines from other world regions, mainly because of the high values of (-)-epigallocatechin and trans-caftaric acid. The products analyzed showed high antioxidant activity, especially the wine samples with values higher than those from wines of different regions of the world.


Apicidin is a histone deacetylase inhibitor with anti-invasive and anti-angiogenic potentials.
Apicidin has been identified as a histone deacetylase (HDAC) inhibitor. Since HDAC inhibitors are emerging as an exciting new class of potential anti-cancer agents, in the present study, we have examined the inhibitory effect of apicidin on cancer invasion and angiogenesis. Apicidin induced di- and tri-acetylated forms of histone H4 and the morphological alteration in v-ras-transformed mouse fibroblast NIH3T3 cells. Apicidin dramatically inhibited the invasion of v-ras-NIH3T3 and human melanoma A2058 cells and it could be associated with its ability to regulate the activities of matrix metalloproteinases. Interestingly, apicidin strongly inhibited the formation of new vessels on chorioallantoic membrane and the tube formation of ECV304 human vascular endothelial cells. This is the first report to show the anti-angiogenic potential of apicidin and it could be developed as a new type of anti-cancer drug.


Laser epiglottectomy: endoscopic technique and indications.
Endoscopic epiglottectomy (epiglottidectomy) may be performed with relative ease and minimal morbidity by using standard microlaryngoscopy techniques and the CO2 laser. Depending on the indications, the removal may be partial or complete. Indications for 51 epiglottectomies included treatment of supraglottic airway obstruction--30 cases; discovery of benign or malignant neoplasm (diagnosis and staging)--20 cases; treatment of malignant neoplasm--7 cases; glottic visualization--4 cases; and treatment of chronic inflammatory conditions--1 case. It is not unusual for a patient to have more than one indication for this procedure. Some epiglottic cancers invade the pre-epiglottic space. This crucial information may not be detectable by MRI or CT scanning techniques. Laser epiglottectomy provides a method to explore and perform a biopsy of the pre-epiglottic space and thereby stage these lesions accurately. There are no significant problems with postoperative alimentation, airway, or voice. Any form of primary or adjuvant therapy can be started without delay.


Trans-Golgi protein TVP23B regulates host-microbe interactions via Paneth cell homeostasis and Goblet cell glycosylation.
A key feature in intestinal immunity is the dynamic intestinal barrier, which separates the host from resident and pathogenic microbiota through a mucus gel impregnated with antimicrobial peptides. Using a forward genetic screen, we have found a mutation in Tvp23b, which conferred susceptibility to chemically induced and infectious colitis. Trans-Golgi apparatus membrane protein TVP23 homolog B (TVP23B) is a transmembrane protein conserved from yeast to humans. We found that TVP23B controls the homeostasis of Paneth cells and function of goblet cells, leading to a decrease in antimicrobial peptides and more penetrable mucus layer. TVP23B binds with another Golgi protein, YIPF6, which is similarly critical for intestinal homeostasis. The Golgi proteomes of YIPF6 and TVP23B-deficient colonocytes have a common deficiency of several critical glycosylation enzymes. TVP23B is necessary for the formation of the sterile mucin layer of the intestine and its absence disturbs the balance of host and microbe in vivo.


Success rates in isolating mesenchymal stem cells from permanent and deciduous teeth.
Stem cells from human exfoliated deciduous teeth (SHED) and human dental pulp stem cells (hDPSCs) have emerged as attractive cell sources for bone regeneration. However, the specific teeth and the conditions most suitable for stem cell isolation remain unclear. Therefore, the success rate of SHED and hDPSCs isolation, the patient age and remaining root length in deciduous teeth were evaluated. Successful isolation was defined as when the cell culture was maintained up to the third passage without any contamination or other issues. Remaining tooth length was calculated using the root-to-crown ratio from patient X-rays and compared to the norm value from the literature. The overall successful isolation rate of SHED and hDPSCs was 82% and 70%. The average patient ages at extraction of the deciduous teeth and permanent teeth were 11 years and 9 months, and 22 years and 10 months respectively. In the successful SHED group, the average remaining root length of the anterior deciduous teeth was 71.4%, and that of the deciduous molars was 61.4%. Successful isolation appears to be associated with patient age, length of the remaining root, and also mechanical stress and other factors. Tooth selection criteria need to be identified to improve the success rate.


Treatment of type II endoleaks after endovascular repair of abdominal aortic aneurysms: transcaval approach.
The purpose of the note is to describe a new technique for type II endoleak treatment, using an alternative approach through femoral venous access. Three patients who developed type II endoleak after endovascular repair of abdominal aortic aneurysm were treated with direct transcaval puncture and embolization inside the aneurysm sac. The detailed technique is described. All patients were treated without any complications and discharged 48 hours after the treatment. At 1 month follow-up the computed tomograph scan did not show a recurrence of a type II endoleak. The management of patients with type II endoleak is a controversial issue and different techniques have been proposed. We suggest an alternative technique for type II endoleak treatment. The feasibility and the advantages of this approach can offer new possibilities for the diagnosis as well as for the treatment of this complication.


Adaptation of existing cutaneous ureterostomy for urinary drainage after renal transplantation.
We adapted existing cutaneous ureterostomies for urinary drainage in 3 patients who underwent renal transplantation. Careful preoperative radiological evaluation of the ureteral anatomy and appropriate preoperative planning are necessary for such patients. The concentration of serum creatinine was 0.9, 1.3 and 1.5 mg. per dl. at 2 months, 3 years and 10 years, respectively, after transplantation. All 3 patients have had bacteriuria that necessitated therapy with chronic suppressive antibiotics but clinical pyelonephritis has not occurred.


Effect of StentBoost imaging guided percutaneous coronary intervention on mid-term angiographic and clinical outcomes.
The gold standard for evaluating stent expansion after percutaneous coronary intervention (PCI) is intravascular ultrasound (IVUS). However, the routine use of this modality is costly and time consuming. StentBoost is a new imaging technique that improves fluoroscopy-based assessments of stent expansion. The purpose of this study was to evaluate the effect of StentBoost imaging-guided PCI on mid-term angiographic and clinical outcomes. A total of 870 consecutive patients were recruited (mean age: 64.34 ± 11.61; men: 64.5%), all of whom underwent PCI with drug-eluting stents (DESs). The subjects were divided into a no StentBoost group (n=569 patients) and a StentBoost group (n=301 patients). The 6-month angiographic and 12-month clinical outcomes were compared between the two groups. At 1 month, clinical outcomes were similar between the two groups. At 6 months, the StentBoost group had significantly lower rates of late loss (0.32 ± 0.40 vs. 0.48 ± 0.59; p=0.005) and binary restenosis (1.2% vs. 8.3%; p=0.029) compared with the no-StentBoost group. At 12 months, StentBoost group had significantly lower the incidence of target lesion revascularization (TLR) (1.7% vs. 7%; p=0.034) and TLR-major adverse cardiac events (6% vs. 13.2%; p=0.037) compared with the no-StentBoost group. We conclude that the routine clinical use of StentBoost during PCI can be useful, and results in better medium-term angiographic and clinical outcomes.


Tonsillectomy reduces the family impact of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and improves health-related quality of life in affected children.
Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder that primarily affects young children, and typically gives rise to fever episodes that recur monthly for several years. This study investigated the impact of PFAPA syndrome on the families of affected children, the health-related quality of life (HRQOL) of children with the syndrome, and how these factors were influenced by tonsillectomy. This prospective cohort study included 24 children with typical PFAPA syndrome that were referred for tonsillectomy, of whom 20 underwent the procedure. The control group consisted of randomly selected children from the general population. Family impact and HRQOL were measured using the standardized, validated questionnaires Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module (FIM) and PedsQL™ 4.0 Generic Core Scales (GCS). Parents to children with PFAPA completed the questionnaires before and 6 months after their child underwent tonsillectomy, and HRQOL was measured both between and during PFAPA episodes. The Wilcoxon signed-rank test was used to compare data before and after tonsillectomy in the patient group, while the Mann-Whitney test was used for comparison of the patient and control groups. Before tonsillectomy, children with PFAPA had significantly lower scores than the control group on the PedsQL™ FIM and the PedsQL™ 4.0 GCS during fever episodes. After tonsillectomy, all patients improved with diminished febrile episodes, which resulted in significantly higher scores regarding both family impact and HRQOL at the time of follow-up. HRQOL of in children with PFAPA improved after tonsillectomy even when compared to afebrile intervals before the procedure. The differences between PFAPA patients and controls were eliminated after tonsillectomy. PFAPA syndrome has a profound negative impact on the families of affected children. Tonsillectomy that leads to cessation or reduction of fever episodes eases the impact of the disease on the family. HRQOL in children with PFAPA is low during febrile episodes and similar to healthy controls in between episodes. The improvement of HRQOL in patients with PFAPA after tonsillectomy compared to the afebrile intervals before tonsillectomy highlights that the constantly recurring fevers may affect the children's well-being even between fever episodes.


Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial.
In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities. SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935. Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression. Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. National Institute of Neurological Disorders and Stroke.


Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in municipal and industrial effluents.
Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) were quantified in 45 effluent samples in the Houston Ship Channel (HSC) system in Texas. Total PCDD/F concentrations ranged from 0.16 to 13.23 pg L(-1) in the dissolved phase and from 0.79 to 682.27 pg L(-1) in the suspended phase. Generally, industrial facilities contained more PCDD/F contamination than municipal wastewater treatment plants or refuse facilities. World Health Organization Toxic Equivalents (WHO-TEQs) ranged from 0.007 to 0.279 pg L(-1) in the dissolved phase and 0.021-1.851 pg L(-1) in the suspended phase. The major TEQ contributor was 2,3,7,8-TCDD and overall, TEQs were greatest in industrial effluents. A correlation between high solids and high PCDD/F concentrations was observed and based on the results obtained in this study, the abundance of suspended solids may have largely contributed to high PCDD/F contamination in the suspended phase. Homolog profiles revealed that PCDD/F contamination increased with increasing chlorination and the highest concentrations were primarily from the octa-chlorinated congeners (OCDD/F) in both the dissolved and suspended phase.


Lipoprotein lipase activity in ischaemic and anoxic myocardium.
Myocardial lipoprotein lipase (LPL) activity during ischaemia has not been fully understood, although it plays an important role in regulating myocardial fatty acid metabolism. In this experiment, the effects of ischaemia (Experiment A) and anoxia (Experiment B) on two distinct fractions of LPL, i.e. functional and nonfunctional forms were investigated in isolated, perfused rat heart. In Experiment A, hearts were perfused by Neely-Morgan working heart mode with Krebs Henseleit bicarbonate (KHB) buffer (95% O2:5% CO2), then whole heart ischaemia was induced by using a one-way aortic valve, simultaneously switching to the same buffer but containing heparin (5 mu/ml) for 20 min. In Experiment B, the hearts were perfused by Langendorff method with KHB buffer (95% O2:5% CO2) and the buffer was switched to KHB (95% N2:5% CO2) containing heparin for 20 min. Coronary effluent was collected at 5 min intervals and used for the measurement of functional LPL activities using 3H-glyceryltrioleate. The hearts were quickly frozen at the end of perfusion and homogenized. The suspension was used for the measurement of non-functional LPL activities. In Experiment A, functional LPL activities in ischaemia were significantly lower than in the aerobic condition. On the contrary, the nonfunctional LPL activity in ischaemia was significantly higher than in the aerobic condition. In Experiment B these values were also significantly lower than in the aerobic condition. However, there was no significant difference in non-functional LPL activity between the anoxia and aerobic condition. These results indicate that there is a conversion defect from the precursor of LPL to the functional form of LPL in ischaemia, whereas disturbed LPL synthesis might be involved in anoxic myocardium.


High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions.
Celiac disease is an immune-mediated disorder in which mucosal autoantibodies to the enzyme transglutaminase 2 (TG2) are generated in response to the exogenous antigen gluten in individuals who express human leukocyte antigen HLA-DQ2 or HLA-DQ8 (ref. 3). We assessed in a comprehensive and nonbiased manner the IgA anti-TG2 response by expression cloning of the antibody repertoire of ex vivo-isolated intestinal antibody-secreting cells (ASCs). We found that TG2-specific plasma cells are markedly expanded within the duodenal mucosa in individuals with active celiac disease. TG2-specific antibodies were of high affinity yet showed little adaptation by somatic mutations. Unlike infection-induced peripheral blood plasmablasts, the TG2-specific ASCs had not recently proliferated and were not short-lived ex vivo. Altogether, these observations demonstrate that there is a germline repertoire with high affinity for TG2 that may favor massive generation of autoreactive B cells. TG2-specific antibodies did not block enzymatic activity and served as substrates for TG2-mediated crosslinking when expressed as IgD or IgM but not as IgA1 or IgG1. This could result in preferential recruitment of plasma cells from naive IgD- and IgM-expressing B cells, thus possibly explaining why the antibody response to TG2 bears signs of a primary immune response despite the disease chronicity.


Implications of the hemodynamic optimization approach guided by right heart catheterization in patients with severe heart failure.
To report the hemodynamic and functional responses obtained with clinical optimization guided by hemodynamic parameters in patients with severe and refractory heart failure. Invasive hemodynamic monitoring using right heart catheterization aimed to reach low filling pressures and peripheral resistance. Frequent adjustments of intravenous diuretics and vasodilators were performed according to the hemodynamic measurements. We assessed 19 patients (age = 48+/-12 years and ejection fraction = 21+/-5%) with severe heart failure. The intravenous use of diuretics and vasodilators reduced by 12 mm Hg (relative reduction of 43%) pulmonary artery occlusion pressure (P<0.001), with a concomitant increment of 6 mL per beat in stroke volume (relative increment of 24%, P<0.001). We observed significant associations between pulmonary artery occlusion pressure and mean pulmonary artery pressure (r=0.76; P<0.001) and central venous pressure (r=0.63; P<0.001). After clinical optimization, improvement in functional class occurred (P< 0.001), with a tendency towards improvement in ejection fraction and no impairment to renal function. Optimization guided by hemodynamic parameters in patients with refractory heart failure provides a significant improvement in the hemodynamic profile with concomitant improvement in functional class. This study emphasizes that adjustments in blood volume result in immediate benefits for patients with severe heart failure.


Effect of bismuth subgallate on nitric oxide and prostaglandin E2 production by macrophages.
Bismuth subgallate (BSG) is used widely in clinics, including Vincent's angina, syphilis, and adenotonsillectomy. This study examined the effects of BSG on nitric oxide (NO) and prostaglandin E2 (PGE2) production in activated RAW 264.7 cells. BSG suppressed production of NO and PGE2 in a dose-dependent manner. BSG could increase TGF-beta1 production, which in turn might promote degradation of iNOS mRNA, thus inhibiting NO production. Additionally, BSG inhibited mPGES protein expression and COX-2 activity in activated RAW 264.7 cells. Exogenous addition of SNP reversed the inhibition effect of PGE2 production by BSG. This behavior indicates that PGE2 inhibition by BSG exerts an indirect effect through NO inhibition.


Comparative Cr, As and CCA induced Cytostaticity in mice kidney: A contribution to assess CCA toxicity.
CCA (Chromium Copper Arsenate) treated wood, widely used in outdoor residential structures and playgrounds, poses considerable dangers of leaching of its components to the environment. In this study, mouse kidney samples were used to evaluate the effects of CCA, chromium trioxide (CrO3) and arsenic pentoxide (As2O5) on cell pathophysiology by flow cytometry. Samples were collected after 14, 24, 48 and 96 h of animal exposure. While Cr had no statistically significant cytostatic effects, As2O5 induced a S-phase delay in animals exposed for 24 h, and over time a G0/G1 phase blockage. The effects of CCA in S-phase were similar, but more severe than those of As2O5. Since environmental and public health hazards due to the long durability of CCA-treated wood products, these data confirm that CCA has profoundly toxic effects on cell cycle, distinct from the compounds themselves. These cytostatic effects support cell cycle dynamics as a valuable endpoint to assess the toxicity of remaining CCA-treated infrastructures, and the expected increased waste stream over the coming decades.


Pelvic exenteration case series: A single surgeon's experience at one institution in Trinidad and Tobago.
Pelvic exenteration (PE) is an ultra-radical surgical procedure characterized by the en bloc resection of the pelvic organs. In this case series, we report retrospectively on four patients who underwent PE in Trinidad and Tobago from 2012 to 2016. One male patient had rectal cancer while one each of three women had cervical, colon, or rectal cancer. Early postoperative complications (≤30days) occurred in all patients, while late complications (>30days) occurred in one patient (Grade 1 - Clavien-Dindo classification). Disease recurrence occurred in 50% of patients, and the median overall survival was 8 months (range, 4-15 months). There are many inherent challenges to conducting such major procedures in developing countries, including inadequate blood product supplies, intensive care unit beds, and pre- and post-operative support services. With increased surgical capacity and support infrastructure, hospitals in these regions would be equipped to perform PEs with better outcomes. This case series adds to existing data on the feasibility of performing PE in developing countries. We demonstrate that PE can be performed without major postoperative complications in a resource-limited hospital. To the best of our knowledge, this is the first case series that describes PE in the Caribbean.


Outcomes of Stenotrophomonas maltophilia hospital-acquired pneumonia in intensive care unit: a nationwide retrospective study.
There is little descriptive data on Stenotrophomonas maltophilia hospital-acquired pneumonia (HAP) in critically ill patients. The optimal modalities of antimicrobial therapy remain to be determined. Our objective was to describe the epidemiology and prognostic factors associated with S. maltophilia pneumonia, focusing on antimicrobial therapy. This nationwide retrospective study included all patients admitted to 25 French mixed intensive care units between 2012 and 2017 with hospital-acquired S. maltophilia HAP during intensive care unit stay. Primary endpoint was time to in-hospital death. Secondary endpoints included microbiologic effectiveness and antimicrobial therapeutic modalities such as delay to appropriate antimicrobial treatment, mono versus combination therapy, and duration of antimicrobial therapy. Of the 282 patients included, 84% were intubated at S. maltophilia HAP diagnosis for duration of 11 [5-18] days. The Simplified Acute Physiology Score II was 47 [36-63], and the in-hospital mortality was 49.7%. Underlying chronic pulmonary comorbidities were present in 14.1% of cases. Empirical antimicrobial therapy was considered effective on S. maltophilia according to susceptibility patterns in only 30% of cases. Delay to appropriate antimicrobial treatment had, however, no significant impact on the primary endpoint. Survival analysis did not show any benefit from combination antimicrobial therapy (HR = 1.27, 95%CI [0.88; 1.83], p = 0.20) or prolonged antimicrobial therapy for more than 7 days (HR = 1.06, 95%CI [0.6; 1.86], p = 0.84). No differences were noted in in-hospital death irrespective of an appropriate and timely empiric antimicrobial therapy between mono- versus polymicrobial S. maltophilia HAP (p = 0.273). The duration of ventilation prior to S. maltophilia HAP diagnosis and ICU length of stay were shorter in patients with monomicrobial S. maltophilia HAP (p = 0.031 and p = 0.034 respectively). S. maltophilia HAP occurred in severe, long-stay intensive care patients who mainly required prolonged invasive ventilation. Empirical antimicrobial therapy was barely effective while antimicrobial treatment modalities had no significant impact on hospital survival. clinicaltrials.gov, NCT03506191.


A hybrid study of multiple contributors to per capita household CO2 emissions (HCEs) in China.
Given the large expenditures by households on goods and services that contribute a large proportion of global CO2 emissions, increasing attention has been paid to household CO2 emissions (HCEs). However, compared with industrial CO2 emissions, efforts devoted to mitigating HCEs are relatively small. A good understanding of the effects of some driving factors (i.e., urbanization rate, per capita GDP, per capita income/disposable income, Engel coefficient, new energy ratio, carbon intensity, and household size) is urgently needed prior to considering policies for reducing HCEs. Given this, in the study, the direct and indirect per capita HCEs were quantified in rural and urban areas of China over the period 2000-2012. Correlation analysis and gray correlation analysis were initially used to identify the prime drivers of per capita HCEs. Our results showed that per capita income/disposable income, per capita GDP, urbanization rate, and household size were the most significantly correlated with per capita HCEs in rural areas. Moreover, the conjoint effects of the potential driving factors on per capita HCEs were determined by performing principal component regression analysis for all cases. Based on the combined analysis strategies, alternative polices were also examined for controlling and mitigating HCEs growth in China.


Assembly of high order G alpha q-effector complexes with RGS proteins.
Transmembrane signaling through G alpha(q)-coupled receptors is linked to physiological processes such as cardiovascular development and smooth muscle function. Recent crystallographic studies have shown how G alpha(q) interacts with two activation-dependent targets, p63RhoGEF and G protein-coupled receptor kinase 2 (GRK2). These proteins bind to the effector-binding site of G alpha(q) in a manner that does not appear to physically overlap with the site on G alpha(q) bound by regulator of G-protein signaling (RGS) proteins, which function as GTPase-activating proteins (GAPs). Herein we confirm the formation of RGS-G alpha(q)-GRK2/p63RhoGEF ternary complexes using flow cytometry protein interaction and GAP assays. RGS2 and, to a lesser extent, RGS4 are negative allosteric modulators of Galpha(q) binding to either p63RhoGEF or GRK2. Conversely, GRK2 enhances the GAP activity of RGS4 but has little effect on that of RGS2. Similar but smaller magnitude responses are induced by p63RhoGEF. The fact that GRK2 and p63RhoGEF respond similarly to these RGS proteins supports the hypothesis that GRK2 is a bona fide G alpha(q) effector. The results also suggest that signal transduction pathways initiated by GRK2, such as the phosphorylation of G protein-coupled receptors, and by p63RhoGEF, such as the activation of gene transcription, can be regulated by RGS proteins via both allosteric and GAP mechanisms.


Leukemia in Iran: Epidemiology and Morphology Trends.
Leukemia accounts for 8% of total cancer cases and involves all age groups with different prevalence and incidence rates in Iran and the entire world and causes a significant death toll and heavy expenses for diagnosis and treatment processes. This study was done to evaluate epidemiology and morphology of blood cancer during 2003-2008. This cross- sectional study was carried out based on re- analysis of the Cancer Registry Center report of the Health Deputy in Iran during a 6-year period (2003 - 2008). Statistical analysis for incidence time trends and morphology change percentage was performed with joinpoint regression analysis using the software Joinpoint Regression Program. During the studied years a total of 18,353 hematopoietic and reticuloendothelial system cancers were recorded. Chi square test showed significant difference between sex and morphological types of blood cancer (P-value<0.001). Joinpoint analysis showed a significant increasing trend for the adjusted standard incidence rate (ASIR) for both sexes (P-value<0.05). Annual percent changes (APC) for women and men were 18.7 and 19.9, respectively. The most common morphological blood cancers were ALL, ALM, MM and CLL which accounted for 60% of total hematopoietic system cancers. Joinpoint analyze showed a significant decreasing trend for ALM in both sexes (P-value<0.05). Hematopoietic system cancers in Iran demonstrate an increasing trend for incidence rate and decreasing trend for ALL, ALM and CLL morphology.


A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study.
Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a < 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. 82 patients with a median defect size of 30 (interquartile range 25-40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.


Nurses' views on change management in health care settings: A qualitative study.
To discover nurses' views on change management processes in health care settings. Because 'change' is an inevitable fact of today's health care environments, developing change management competencies at all levels is a must to survive and compete for the organisations and professionals in the health care systems. A descriptive qualitative approach was used. The sample consisted of 18 nurses reached by using snowball sampling. The data were collected through semi-structured interviews and analysed using the Colaizzi method in the NVivo12 program. The results of the study were collected under three main themes: 'general approaches and initial responses to change', 'factors affecting attitudes toward change' and 'strategic mistakes made by managers during the change process'. The study showed that nurses show different reactions to change. Their attitudes towards change could be affected positively and negatively by the relevant factors. Nurses thought that managers were making strategic mistakes during the change process. Recognizing the approaches of nurses and managers towards change and increasing awareness of the mistakes during the change process may contribute to the achievement of the change processes in health care settings.


Aggregation of tetrameric acids in aqueous media studied by small-angle neutron scattering.
This article presents the characterization of two self-associated structures, a C(80)-tetraacid (also known as ARN), which is an aliphatic molecule present in crude oil and responsible for the formation of deposits, and BP-10, a molecule designed to model the properties of the C(80)-tetraacid. These molecules have four carboxylic functions at the end of four interconnected hydrocarbon chains and can be dissolved in aqueous solution and in basic media. In this paper we have used small-angle neutron scattering (SANS) as the main method to study the tetrameric acids in solution. SANS measurements show that the two molecules (in sodium form) exhibit very different types of aggregation properties in aqueous solution. More specifically, Na(4)BP-10 forms nanometer-sized micelles with an aggregation number close to 5 (at concentrations above the critical micellar concentration) in both 20 mM NaCl and 0.9 wt.% 1-butanol media. On the contrary fully ionised C(80)-TA forms very large structures in pure D(2)O and NaCl 20 mM, so large that their exact dimensions could not be determined by SANS.