LncRNA NEAT1 aggravates lipopolysaccharide-induced acute lung injury by regulating the miR-98-5p/TLR4 axis.
Although long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be associated with acute lung injury (ALI), its specific mechanism has not been well studied. Mouse and cell ALI models were constructed by lipopolysaccharide (LPS). Cell viability was evaluated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide assay. Cell death was evaluated by lactate dehydrogenase release (LDH) detection kit and flow cytometry. The levels of cytokines in lung tissues lysates were detected by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The expression of apoptosis-related markers was detected by Western blot. The relationship between NEAT1, miR-98-5p, and toll-like receptor 4 (TLR4) was determined by bioinformatics prediction, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Rescue experiments were performed to determine the role of NEAT1/miR-98-5p/TLR4 in ALI. NEAT1 was significantly upregulated during ALI both in vitro and in vivo. NEAT1 knockdown efficiently attenuated LPS-induced ALI and reduced LPS-induced elevation of cytokines both in vitro and in vivo. NEAT1 negatively regulated miR-98-5p by directly sponging it, and TLR4 was a target of miR-98-5p. MiR-98-5p inhibition or TLR4 overexpression could obviously attenuate the protective effects of NEAT1 knockdown in LPS-treated A549 cells. Our study demonstrated that NEAT1 knockdown alleviated LPS-induced ALI by targeting the miR-98-5p/TLR4 axis.


Experimental evidences for reducing Mg activation energy in high Al-content AlGaN alloy by MgGa δ doping in (AlN)m/(GaN)n superlattice.
P-type doping in high Al-content AlGaN alloys is a main challenge for realizing AlGaN-based deep ultraviolet optoelectronics devices. According to the first-principles calculations, Mg activation energy may be reduced so that a high hole concentration can be obtained by introducing nanoscale (AlN)5/(GaN)1 superlattice (SL) in Al0.83Ga0.17N disorder alloy. In this work, experimental evidences were achieved by analyzing Mg doped high Al-content AlGaN alloys and Mg doped AlGaN SLs as well as MgGa δ doped AlGaN SLs. Mg acceptor activation energy was significantly reduced from 0.378 to 0.331 eV by using MgGa δ doping in SLs instead of traditional doping in alloys. This new process was confirmed to be able to realize high p-type doping in high Al-content AlGaN.


Renal sodium handling and nighttime blood pressure.
Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure.


Collaborative care: Primary health workforce and service delivery in Western New South Wales-A case study.
To explore how four small towns in rural New South Wales known as the 4Ts are addressing challenges accessing quality care and sustainable health services through a collaborative approach to workforce planning using the collaborative care framework. Descriptive case study approach. The collaborative care project was developed as a result of ongoing partnerships between 2 rural Local Health Districts, 2 Primary Health Networks and a non-governmental health workforce organisation. The collaboration works with 5 subregions each comprising 2 or more rural communities. This paper focuses on the 4Ts subregion. Stakeholders of the collaborative design including organisations and the community. A place-based approach to co-designing health services with community in one sub-region of Western New South Wales. A synthesis of field observations and experiences of community and jurisdictional partners in implementation of the 4Ts subregional model. Mapping of implementation processes against the collaborative care framework. The collaborative care framework is a useful planning and community engagement tool to build health workforce literacy and to impact on system change at the local level. We identify key elements of effectiveness in establishing the 4Ts model, including the need for coordinated health system planning, better integrating existing resources to deliver services, community engagement, building health workforce literacy and town-based planning. This study adds to the body of knowledge about how to successfully develop a collaborative primary health care workforce model in practice. The findings demonstrate that the implementation of a collaborative primary health care workforce model using the collaborative care framework can improve service access and quality, which in turn might facilitate workforce sustainability.


Characterization of a novel end product tolerant and thermostable cellulase from Neobacillus sedimentimangrovi UE25.
Recent advancements in biorefinery processes necessitate search for cost effective and thermostable cellulases. This study was designed to characterize the cellulase obtained from a thermophilic bacterium, Neobacillus sedimentimangrovi UE25. A combined pretreatment of NaOH and methyltrioctylammonium chloride was given to sugarcane bagasse (SB) for lignin removal and the pretreated SB was utilized as a carbon source for the cellulase production. The thermostable cellulase thus obtained was characterized by adopting central composite design which has not been reported earlier for this purpose. Cellulase showed its maximum activity at pH 7 and temperature 60 ℃ and it remained active in the presence of many salts and detergents. Endoglucanase (EG) was found to be stable for 30 min at 80 ℃. The purification of EG by using DEAE column yielded specific activity and purification fold of 365.866 IU mg-1 and 4.264, respectively. The purified EG had a molecular weight of ∼45 kDa. End product tolerance of EG was also evident, as an activity of 228.57 IU mL-1 was observed in the presence of 60 mM glucose which revealed that it does not lose its activity upon accumulation of end-product when the reaction is prolonged. The purified EG exhibited Vmax and Km of 294 U mL-1 min-1 and 36 µM, respectively, in the presence of 60 mM glucose. This novel thermostable cellulase can finds its applications in industrial sector.


Sudden cardiac arrest in patients with preserved left ventricular systolic function: a clinical dilemma.
Stratifying the risk for sudden cardiac arrest (SCA) in individuals with preserved systolic function remains a pressing public health problem. Current guidelines for the implantation of cardiac defibrillators largely ignore patients with preserved systolic function, even though they account for the majority of cases of SCA. Risk stratification for such individuals may be increasingly feasible. Notably, most individuals who experience SCA have structural heart disease, even if undiagnosed. Thus, clinical risk scores have been developed to identify individuals at high risk. Moreover, there are now promising data that T-wave alternans, alone and in combination with other indices, effectively predicts SCA in this population. This article presents our current understanding of SCA caused by ventricular arrhythmias in patients with preserved left ventricular systolic function, and attempts to build a framework to predict risk in this population.


Handling outliers in brain tumour MRS data analysis through robust topographic mapping.
Uncertainty is inherent in medical decision making and poses a challenge for intelligent technologies. This paper focuses on magnetic resonance spectra (MRS) for discrimination of brain tumour types and grades. Modelling of this type of high-dimensional data is commonly affected by uncertainty caused by the presence of outliers. Multivariate data clustering and visualization of MRS data is proposed using the GTM framework with basis functions comprising Student t-distributions in order to minimize the negative impact on the model from outliers. The effectiveness of this model on the MRS data is demonstrated empirically.


Establishment of a Lymph Node Metastasis-Associated Prognostic Signature for Lung Adenocarcinoma.
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors at the time of diagnosis, especially lymph node metastasis (LNM). This study aimed to construct a LNM-related gene signature for predicting the prognosis of patients with LUAD. RNA sequencing data and clinical information of LUAD patients were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Samples were divided into metastasis (M) and nonmetastasis (NM) groups based on LNM status. Differentially expressed genes (DEGs) between M and NM groups were screened, and then WGCNA was applied to identify key genes. Furthermore, univariate Cox and LASSO regression analyses were conducted to construct a risk score model, and the predictive performance of model was validated by GSE68465, GSE42127, and GSE50081. The protein and mRNA expression level of LNM-associated genes were detected by human protein atlas (HPA) and GSE68465. A prognostic model based on eight LNM-related genes (ANGPTL4, BARX2, GPR98, KRT6A, PTPRH, RGS20, TCN1, and TNS4) was developed. Patients in the high-risk group had poorer overall survival than those in the low-risk group, and validation analysis showed that this model had potential predictive value for patients with LUAD. HPA analysis supported the upregulation of ANGPTL4, KRT6A, BARX2, RGS20 and the downregulation of GPR98 in LUAD compared with normal tissues. Our results indicated that the eight LNM-related genes signature had potential value in the prognosis of patients with LUAD, which may have important practical implications.


Bilateral interconnected latissimus dorsi-gluteus maximus muscular cutaneous flaps for closure of subfascial infections in lumbar spinal surgery. A technical note.
A surgical technique for primary closure of postoperative subfascial infections is described. To describe the methods and indications for the use of the interconnected latissimus dorsi-gluteus maximus flap. Closure of subfascial postoperative infection can be complicated by soft tissue defects and retained implants. Healing by secondary intention is expensive and gives unpredictable coverage of retained hardware. A bilateral interconnected latissimus dorsi-gluteus maximus flap was used to cover resultant soft tissue defects according to techniques previously described for the delayed primary closure of myelomeningocele defects. Stable, durable, drainage-free soft tissue coverage was obtained in all patients treated with this technique. The latissimus dorsi-gluteus maximus flap represents an effective, economical option for the treatment of patients with subfascial infection after instrumented spinal fusion surgery.


Perinatal gangrene of the buttock: an iatrogenic or spontaneous condition?
Three cases of neonatal gangrene of the buttock are reported. They were characterized by: localization to the skin and muscles of one buttock; sudden onset, minutes after birth; sciatic palsy in two of three and absence of known causes, except for an umbilical injection at birth in two of three. This procedure seems responsible in the first two; the etiology of the apparently spontaneous third case is discussed.


X inactivation Xplained.
Random inactivation of one of the two female X chromosomes establishes dosage compensation between XY males and XX females in placental mammals. X inactivation is controlled by the X inactivation center (Xic). Recent advances in genome sequencing show that the Xic has evolved from an ancestral vertebrate gene cluster in placental mammals and has undergone separate rearrangements in marsupials. The Xic ensures that all but one X chromosome per diploid genome are inactivated. Which chromosome remains active is randomly chosen. Pairing of Xic loci on the two X chromosomes and alternate states of the X chromosomes before inactivation have recently been implicated in the mechanism of random choice. Chromosome-wide silencing is then initiated by the noncoding Xist RNA, which evolved with the mammalian Xic and covers the inactive X chromosome.


Hepatic resection for colorectal metastases in the caudate lobe of the liver.
Although hepatic resections for colorectal metastases have become established procedures, there is still only a small number of reports of hepatic resections for such metastases in the caudate lobe. From 1993 to 2001, seven patients underwent eight hepatic resections for colorectal metastases in the caudate lobe at our department. The patients were five men and two women, and their ages were from 53 to 73 years. The ratio of synchronous to metachronous liver metastases was 2 : 5. Solitary metastasis was observed in one patient. One patient with a metastasis in the Spiegel lobe and three patients with metastasis in the caudate process underwent partial resection of the site. The other patients underwent resection of the Spiegel lobe (two times), resection of the right-sided caudate lobe, and total caudate lobe resection. The mean (+/-SE) operative time was 315.9 +/- 30.6 min. Mean intraoperative blood loss was 1325.9 +/- 421.1 ml, and mean postoperative hospital stay was 21 +/- 3.7 days. One patient, who underwent sigmoidectomy and hepatectomy as an emergency operation due to ileus, experienced wound infection. No patient died within 12 months after the surgery. Five patients were alive at 24 months, and three at 36 months. The outcome of these patients encourages us to continue performing hepatic resection for colorectal metastases in the caudate lobe, as it is assumed to be a safe and effective procedure.


Does the increased motion probing gradient directional diffusion tensor imaging of lumbar nerves using multi-band SENSE improve the visualization and accuracy of FA values?
Diffusion tensor imaging (DTI) is useful to evaluate lumbar nerves visually and quantitatively. Multi-band sensitivity encoding (MB-SENSE) is a technique to reduce the scan time. This study aimed to investigate if super-multi-gradient DTI with multi-band sensitivity encoding (MB-SENSE) is better in evaluating lumbar nerves than the conventional method. The participants were 12 healthy volunteers (mean age 33.6 years). In all subjects, DTI was performed using echo planar imaging with different motion probing gradient (MPG) directions (15 without MB, and 15, 32, 64, and 128 with MB) and the lumbar nerve roots were visualized with tractography. In the five groups, we evaluated the resultant DTI both visually and quantitatively. For visual measures, we counted the number of fluffs and disruptions of the nerve fibers. For quantitative measures, the fractional anisotropy (FA) and standard deviation of the fractional anisotropy (FA-SD) values at two regions (proximal and distal) of the lumbar nerve roots were quantified and compared. Among the five groups, the number of fluffs decreased as the number of MPG directions increased. However, the number of disruptions showed no significant differences. The FA-SD values decreased as the number of MPG directions increased, indicating that the signal variation was reduced with multi-gradient directional DTI. High-resolution multi-directional DTI with MB-SENSE may be useful to visualize nerve entrapments and may allow for more accurate DTI parameter quantification with opportunities for clinical diagnostic applications.


Real-World Effectiveness of Sodium Glucose Co-Transporter-2 Inhibitors in Japanese Patients with Diabetes Mellitus.
Sodium glucose co-transporter-2 inhibitors (SGLT2i) have been on the market for 5 years in Japan. We explored the real-world effectiveness of SGLT2i in Japan. We retrospectively analyzed two large Japanese administrative databases from JMDC Inc.: insurance-dataset (I-dataset) and Medical Data Vision Co. Ltd. [hospital-dataset (H-dataset)]. Patients who newly started SGLT2i or other oral antidiabetic drugs (OADs) between 1 April 2014 and 31 March 2016 were selected for this analysis and followed for 1 year from the index date. Changes in glycated hemoglobin (HbA1c), body mass index (BMI), and estimated glomerular filtration rate (eGFR) were evaluated during the 1-year period. A total of 127,961 patients in the H-dataset and 26,436 in the I-dataset were included in this analysis. Baseline HbA1c, BMI, and eGFR levels tended to be higher in SGLT2i users than in other OAD cohorts. After 1 year, 44.3% (I-dataset) and 53.3% (H-dataset) of SGLT2i users and 33.0-44.2% (I-dataset) and 47.0-58.1% (H-dataset) of other users were still on their medications. The mean HbA1c level decreased by - 0.7 to - 0.9% in SGLT2i users versus - 0.4 to - 1.5% in the other cohorts. The mean BMI decreased by - 0.8 kg/m2 in SGLT2i users whereas the change in other cohorts was - 0.5 to 0.4 kg/m2. No clinically relevant changes in eGFR were observed over the period. This study showed that around half of the SGLT2i users were still on medication after 1 year from treatment initiation. Initiation of SGLT2i was associated with improvement in HbA1c and BMI, with no abnormal changes in renal function observed in the first year following treatment. These findings support the results from clinical trials and will expand the existing evidence of SGLT2i use in real-life practice in Japan. Astellas Pharma Inc., Tokyo, Japan.


Functional capacities of tactile afferent fibres in neonatal kittens.
1. Responses were recorded from individual tactile afferent fibres isolated by microdissection from the median nerve of pentobarbitone-anaesthetized neonatal kittens (1-5 days post-natal age). Experiments were also conducted on adult cats to permit precise comparisons between neonatal and adult fibres.2. Neonatal fibres with receptive fields on the glabrous skin of the foot pads were classified into two broad groups, a slowly adapting class (40%) which responded throughout a 1 sec period of steady indentation and a rapidly adapting or dynamically sensitive class comprising 60% of units. Fibres in these two groups had overlapping conduction velocities in the range 4.3 to 7.5 m/sec and were believed to be the developing Group II afferents of the adult.3. Neonatal slowly adapting fibres qualitatively resembled their adult counter-parts. They displayed graded stimulus-response relations which, over the steepest segment of the curves, had mean slopes of 15.7 impulses/100 mum of indentation. Plateau levels of response were often reached at amplitudes of skin indentation of < 0.5-0.7 mm.4. Dynamically sensitive fibres with receptive fields on the glabrous skin were studied using sinusoidal cutaneous vibration which in the adult enables them to be divided into two distinct classes. However, in the neonate, they formed a continuum whether criteria of sensitivity or responsiveness were used.5. In response to vibration neonatal fibres differed from adult ones according to the following quantitative indices: (i) sensitivity as measured by both absolute thresholds and thresholds for a 1: 1 pattern of response, both of which were higher in the neonate than in the adult at all frequencies > 50 Hz and differed by an order of magnitude at frequencies >/= 200 Hz; (ii) responsiveness based on the mean impulse rate evoked at a fixed amplitude of cutaneous vibration; (iii) band width of vibratory sensitivity which in the neonate was confined to approximately 5-300 Hz whereas in the two classes of adult units it covered the range 5-800 Hz; (iv) capacity for coding information about vibration frequency. Impulse activity of neonatal fibres was less tightly phase-locked to the vibratory stimulus and showed a poorer reflection of the periodic nature of the vibratory stimulus than impulse patterns of adult units.6. The results reveal that tactile receptors and afferent fibres in the neonate are functionally immature. Their restricted coding capacities suggest that peripheral tactile sensory mechanisms impose limits on the ability of the new-born animal to derive information about its tactile environment.


Differential diagnosis of Crohn's disease and intestinal tuberculosis in patients with spontaneous small-bowel perforation.
Spontaneous small-bowel perforation caused by Crohn's disease (CD) or intestinal tuberculosis (ITB) is a rare disease entity. We investigated the clinical features and radiologic findings of patients with CD or ITB who presented with a spontaneous small-bowel perforation. Between January 2001 and December 2010, sixty-two patients underwent surgery due to a spontaneous small-bowel perforation, including 21 (33.9%) CD patients and 18 (29.0%) ITB patients. Clinical and radiologic features were compared between CD and ITB patients. The mean age was significantly lower in CD patients than in ITB patients (p = 0.014). Diarrhea was more common in CD. By contrast, night sweating and a previous history of tuberculosis were more common in ITB. Only 27.8% of patients with ITB had a positive QuantiFERON-TB Gold test. CT findings such as bowel wall thickening of more than 10 mm, omental thickening, and intra-abdominal lymphadenopathy larger than 10 mm were more common among perforations caused by ITB. Mesenteric fat infiltration was a more frequent finding in CD than in ITB. Clinical symptoms and radiologic findings may aid in the differential diagnosis between CD and ITB in patients presenting with spontaneous small-bowel perforation.


Ozonation of imidacloprid in aqueous solutions: reaction monitoring and identification of degradation products.
This paper presents the degradation of imidacloprid by ozonation. Solutions of 39.0 μg/mL imidacloprid were prepared either by dissolution of standard or by dilution of Gaucho Blé(®) seed loading solution and then ozonated under different conditions. The concentration of imidacloprid and oxidation products in both solutions was monitored by HPLC-UV as a function of the treatment time for a concentration of 100g/m(3) of ozone in the inlet gas. No significant difference was observed: in both cases, imidacloprid degradation was a pseudo-first order reaction with similar reaction rates (0.129-0.147 min(-1)), degradation by-products with the same HPLC retention times were observed and their concentrations as a function of the treatment time followed a very similar trend. The study of ozone concentration in the inlet gas (from 25 to 100g/m(3)) showed that imidacloprid degradation is also a first-order reaction with respect to ozone. The ozonation by-products were then collected and identified by ESI(+)-MS. A degradation pathway of imidacloprid was finally proposed.


Transport, retention, and long-term release behavior of polymer-coated silver nanoparticles in saturated quartz sand: The impact of natural organic matters and electrolyte.
This study investigated the transport and long-term release of stabilized silver nanoparticles (AgNPs), including polyvinylpyrrolidone-coated AgNPs (PVP-AgNPs) and bare AgNPs (Bare-AgNPs), in the presence of natural organic matters (NOMs; both humic acids (HA) and alginate (Alg)) and an electrolyte (Ca2+) in a sand-packed column. Very low breakthrough rate (C/C0) of AgNPs (below 0.04) occurred in the absence of NOM and the electrolyte. Increasing the concentration of NOM and decreasing the influent NOM solution's ionic strength (IS) reduced the retention of AgNPs. The reduced NP retention at high NOM and low IS was mainly attributed to the increased energy barrier between the AgNPs and the sand grain surface. Notably, the retention of PVP-AgNPs was enhanced at high Alg concentration and low IS, which mainly resulted from the improved hydrophobicity that could increase the interaction between the PVP-AgNPs and the collector. The total release amount of PVP-AgNPs (10.03%, 9.50%, 28.42%, 6.37%) and Bare-AgNPs (3.28%, 2.58%, 10.36%, 1.54%) were gained when exposed to four kinds of NOM solutions, including deionized water, an electrolyte solution (1 mM Ca2+), HA with an electrolyte (1 mM Ca2+), and a Alg (40 mg/L) solution with an electrolyte (1 mM Ca2+). The long-term release of retained silver nanoparticles in the quartz sand was mostly through the form of released Ag NPs. The factors that increased the mobility of AgNPs in quartz sand could improve the release of the AgNPs. The release of AgNPs had no significant change in the presence Ca2+ but were increased in the presence of HA. The Alg slightly decreased the release of AgNPs by increasing the hydrophobicity of AgNPs. The results of the study indicated that all the tested NOM and Ca2+ have prominent influence on the transport and long-term release behavior of silver nanoparticles in saturated quartz sand.


The role of the prosthodontist in restoring root-resected molars: a study of 70 molar root resections.
Root resection is a complex, multidiscipline technique to eliminate molar furcation invasions. In the short term of 3 or 4 years it has been highly successful, but after 10 years approximately one third fail. A substantial number of failures were attributed to recurrent periodontal disease. This study examined 70 root resected molars in 62 patients for the quality of the resections. Twenty-one (30%) of the resections were considered faulty when subgingival, residual roots, furcal lips, and/or ledges were present. Failures were more frequent in maxillary molars (33.3%) than mandibular molars (22.7%). Clinically hidden roots/lips and ledges in mandibular molars were readily observed in radiographs, but were seen radiographically only 37.5% of the time in maxillary molars. Since subgingival defects are believed to encourage future periodontal disease, it is important that the dentist detect these structures and correct them before proceeding with the permanent restoration.


Comparative accuracy of the vectorcardiogram and electrocardiogram in the localization of the accessory pathway in patients with Wolff-Parkinson-White syndrome: validation of a new vectorcardiographic algorithm by intraoperative epicardial mapping and electrophysiologic studies.
The scalar electrocardiograms (ECGs) and vectorcardiograms (VCGs) of 41 patients with Wolff-Parkinson-White (WPW) syndrome were used to compare the accuracy of these techniques in the identification of the site of preexcitation. The location of the accessory pathway (AP) was determined by endocavitary electrophysiologic studies in all patients and the location was confirmed during intraoperative epicardial mapping in 28 of them. The ECGs were classified according to Gallagher's criteria and with Milstein's algorithm, whereas the VCGs were classified according to a new two-step algorithm. The presence of multiple accessory pathways and coexisting myocardial infarctions were major limitations in both the VCG and ECG classification procedures. In patients with a single accessory pathway, three AP localizations (right free ventricular wall, posterior, or left free ventricular wall) were identified with the first step of the VCG algorithm, with an overall sensitivity (96.5%), specificity (90.7%), and positive predictive values (80%) that were greater than those obtained with the ECG Milstein algorithm (77.1%, 91.5%, and 75%, respectively). The second step of the VCG algorithm made it possible to identify an AP location in one of the following sites: anterior right, lateral right, posterior right, posterior left, lateral left, or anterior left ventricle. The overall sensitivity, specificity, and positive predictive values were greater for the second step of the VCG algorithm than for the ECG criteria proposed by Gallagher (43.6% versus 39.3%, 92.1% versus 87.4%, and 51.5% versus 33.3%, respectively). It was concluded that the VCG seems to be more specific and sensitive than the ECG in the identification of the preexcitation site and should be given preference in the initial evaluation of the WPW syndrome.


Assisted reproductive technology and neurodevelopmental outcomes in offspring: a prospective birth cohort study in East China.
Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception? In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results. In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups. At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.


Propagation of human corneal endothelium in vitro effect of growth factors.
Endothelial cells were obtained from 23 human corneal-scleral rims. Donors were 0.2-37 yr of age. Most cultures obtained from donors under 30 yr ceased to grow after the seventh passage (3-24 weeks). Growth from 17- and 25-yr-old donors were maintained for nine passages (26 weeks) and 18 passages (100 weeks), respectively. Cultures were established from 12 rims, using growth factors in uncoated culture flasks or epidermal growth factor (EGF) in an extracellular matrix-coated (ECM) flask. EGF improved the growth potential of the cells; a combination of an ECM-coated-tissue culture flask with EGF in the medium provided an improved environment for continuous growth.


Storage media and not extraction method has the biggest impact on recovery of bacteria from the oral microbiome.
Next Generation sequencing has greatly progressed the exploration of the oral microbiome's role in dental diseases, however, there has been little focus on the effect of sample storage conditions and their interaction with DNA extraction method. Dental plaque samples collected from 20 healthy participants were pooled and stored in either 75% ethanol or Bead solution for up to 6-months at -80 °C, prior to DNA extraction with either QIAamp (non-bead beating) or PowerSoil (bead-beating) kit, followed by Illumina sequencing of 16S rRNA gene. We found that storage media and not extraction method had the biggest influence on the diversity and abundance of the oral microbiota recovered. Samples stored in Bead solution, independent of the extraction kit, retrieved higher diversity (PowerSoil p = 1.64E-07, QIAamp p = 0.0085) and had dissimilar overall ecologies as indicated by lower level of shared diversity (PowerSoil p = 0.0000237, QIAamp p = 0.0088). Comparatively, samples stored in Bead solution and extracted with PowerSoil recovered a higher abundance of Streptococcus species. These data indicate that Bead solution can preserve the oral microbiome in dental plaque reliably, for periods of up to 6-months at -80 °C, and is compatible, with either a bead-beating or non-bead beating DNA extraction method.


The role of the GAF and central domains of the transcriptional activator VnfA in Azotobacter vinelandii.
VnfA is a transcriptional activator that is required for the expression of the structural genes encoding nitrogenase-2 in Azotobacter vinelandii. VnfA consists of three domains: an N-terminal regulatory domain termed GAF, including a Cys-rich motif; a central domain from the AAA+ family; and a C-terminal domain for DNA binding. Previously, we reported that transcriptionally active VnfA harboring an Fe-S cluster (presumably of the 3Fe-4S type) as a prosthetic group and the Cys-rich motif were possibly associated with coordination of the Fe-S cluster. In the present study, we have investigated the roles of the GAF and central domains in the regulatory function of VnfA using truncated variants: ΔN15(VnfA) and ΔGAF(VnfA) that lack the N-terminal 15 residues and whole GAF domain, respectively, and GAF(VnfA) consisting of only the GAF domain. ΔN15(VnfA) and ΔGAF(VnfA) lost the ability to bind the Fe-S cluster, whereas GAF(VnfA) was still able to bind to the cluster, consistent with the hypothesis that the Cys-rich motif is essential for Fe-S cluster binding. The GAF domain showed an inhibitory effect on the transcriptional activity of VnfA, which was reversed in the presence of the Fe-S cluster, and reactivated upon disassembly of the cluster. The inhibitory activity of the GAF domain acts on the NTPase activity of the central domain, whereas the binding ability of VnfA to DNA was not significantly affected, when VnfA retains its tetrameric conformation. The results imply that a major pathway, by which VnfA function is regulated, operates via the control of NTPase activity by the GAF domain.


A Randomized, Open-Label Comparison of Once-Weekly Insulin Icodec Titration Strategies Versus Once-Daily Insulin Glargine U100.
Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults (n = 205) with type 2 diabetes and HbA1c 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment ±21 units/week; n = 51), B (80-130 mg/dL; ±28 units/week; n = 51), or C (70-108 mg/dL; ±28 units/week; n = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80-130 mg/dL; ±4 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring. TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04; P = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia. Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80-130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia.


Self-injury in autism spectrum disorder: an effect of serotonin transporter gene promoter variants.
Self-injurious behavior in autism spectrum disorder (ASD) has been associated with lower whole blood serotonin levels and the role of serotonin transporter gene promoter region (5HTTLPR) polymorphisms is of interest because of their effects on transporter functioning. This study examined the association between self-injurious behavior in ASD and allelic frequencies of 5HTTLPR. Sixty-four children and adolescents with ASD who were not taking serotonergic medication at the time of the assessment were included in the analysis. Self-injury was assessed using the Autism Diagnostic Interview-Revised (ADI-R) and whole blood serotonin levels were measured using high-pressure liquid chromatography (HPLC) with fluorometic detection. DNA was extracted from saliva and PCR amplified with fluorescent primers. Self-injury significantly increased with the number of La alleles of the 5HTTLPR and decreased with the number of Lg alleles. Self-injury in ASD may be associated with a specific genotype of the serotonin transporter gene promoter region. Future studies should continue to explore subgroups to clarify the underlying clinical and genetic heterogeneity in ASD.


Do PEEK Rods for Posterior Instrumented Fusion in the Lumbar Spine Reduce the Risk of Adjacent Segment Disease?
Polyetheretherketone (PEEK) rods were clinically introduced in the mid-2000s as an alternative to titanium (Ti) rods for posterior instrumented lumbar spine fusion, theorized to reduce the risk of adjacent segment disease (ASD). However, few studies have follow-up beyond 2 years. Consequently, we conducted a matched cohort study using data from Kaiser Permanente's spine registry to compare the 2 rod systems and risk for outcomes. Patients aged ≥18 undergoing first posterior lumbar fusion for a degenerative diagnosis from 2009 to 2018 using either a PEEK or a Ti rod were identified. Fusions using Ti rods were 2:1 propensity score matched to PEEK rods on the following factors: patient age, body mass index, smoking, American Society of Anesthesiologists classification, diagnosis, interbody use, bone morphogenic protein use, number of levels fused, fusion levels, and operative year. The matched sample included 154 PEEK and 308 Ti fusions. We used Cox regression to evaluate ASD and nonunion, and logistic regression to evaluate 90-day emergency department (ED) visit, readmission, and complication. We did not observe a difference in risk for ASD (hazard ratio = 1.02, 95% confidence interval [CI] = 0.66-1.59) or ED visit (odds ratio [OR] = 0.88, 95% CI = 0.48-1.59). A lower likelihood of readmission (OR = 0.34, 95% CI = 0.13-0.94) was observed following PEEK fusion compared with Ti. No nonunions or 90-day complications were observed for the PEEK group; 5 (2-year cumulative incidence = 0.7%) nonunions and 4 (1.3%) complications were observed for the Ti group. Our multicenter study did not support the hypothesis that PEEK rods are associated with a lower ASD risk. Reasons for readmission need to be identified to better understand the differences observed here. Further study of patients with TLIF using Ti and PEEK rods and posterolateral fusion with Ti and PEEK rods is needed. The present study adds to the literature supporting their midterm effectiveness of PEEK rods compared with Ti rods for both their safety and their effectiveness at the 5-7-year follow-up. 3.


The influence of support and medical data on the level of illness acceptance, the way of coping with a stressful situation, and mental adjustment to the disease among cancer patients.
The aim of this study was to analyze the behavior of cancer patients. This survey-based study involved 145 oncological patients and was conducted from July to November 2018. It was performed using an author's questionnaire and three standardized tools: the mini-Mental Adjustment to Cancer Scale, the Acceptance of Illness Scale, and the Coping Inventory for Stressful Situations. The acceptance of illness was at a medium level. Patients who had been ill for longer time periods coped with stress better (p < 0.071) and showed better mental adjustment (p < 0.05 for Positive Redefinition, and p < 0.08 for Fighting Spirit). Patients with benign tumors focused on emotions (p < 0.001) and avoidance (p < 0.005) and were preoccupied with anxiety (p < 0.05). Longer treatment time was associated with a higher ability to cope with stress (p < 0.05). Patients receiving support were characterized by Anxious Preoccupation attitude (p < 0.1), and those who had not got it by Fighting Spirit (p < 01). Cancer patients have problems coping with new circumstances. They need support and help to understand and accept their situation.


Pancreatic neuroendocrine tumor in a child of 3.5 years old.
Pancreatic neuroendocrine tumor is rarely seen, particularly in children. One of the symptoms of this tumor is jaundice that may be misdiagnosed as the sign of hepatitis A, especially in countries with a high prevalence of this infectious disease. We present a 3.5-year-old girl with four weeks of icterus, who was misdiagnosed with hepatitis A. The patient was finally diagnosed as having a low grade pancreatic neuroendocrine carcinoma. Pediatricians should be aware of or consider a tumor in differential diagnosis of jaundice, especially prolonged one in children.


Molecular Epidemiology of Norovirus (NoV) Infection in Mie Prefecture: The Kinetics of Norovirus Antigenemia in Pediatric Patients.
Few studies have shown the presence of norovirus (NoV) RNA in blood circulation but there is no data on norovirus antigenemia. We examined both antigenemia and RNAemia from the sera of children with NoV infections and studied whether norovirus antigenemia is correlated with the levels of norovirus-specific antibodies and clinical severity of gastroenteritis. Both stool and serum samples were collected from 63 children admitted to Mie National Hospital with acute NoV gastroenteritis. Norovirus antigen and RNA were detected in sera by ELISA and real-time RT-PCR, respectively. NoV antigenemia was found in 54.8% (34/62) and RNAemia in 14.3% (9/63) of sera samples. Antigenemia was more common in the younger age group (0-2 years) than in the older age groups, and most patients were male. There was no correlation between stool viral load and norovirus antigen (NoV-Ag) levels (rs = -0.063; Cl -0.3150 to 0.1967; p = 0.6251). Higher levels of acute norovirus-specific IgG serum antibodies resulted in a lower antigenemia OD value (n = 61; r = -0.4258; CI -0.62 to -0.19; p = 0.0006). Norovirus antigenemia occurred more commonly in children under 2 years of age with NoV-associated acute gastroenteritis. The occurrence of antigenemia was not correlated with stool viral load or disease severity.


Master Blaster: an approach to sensitive identification of remotely related proteins.
Genome sequencing projects unearth sequences of all the protein sequences encoded in a genome. As the first step, homology detection is employed to obtain clues to structure and function of these proteins. However, high evolutionary divergence between homologous proteins challenges our ability to detect distant relationships. In the past, an approach involving multiple Position Specific Scoring Matrices (PSSMs) was found to be more effective than traditional single PSSMs. Cascaded search is another successful approach where hits of a search are queried to detect more homologues. We propose a protocol, 'Master Blaster', which combines the principles adopted in these two approaches to enhance our ability to detect remote homologues even further. Assessment of the approach was performed using known relationships available in the SCOP70 database, and the results were compared against that of PSI-BLAST and HHblits, a hidden Markov model-based method. Compared to PSI-BLAST, Master Blaster resulted in 10% improvement with respect to detection of cross superfamily connections, nearly 35% improvement in cross family and more than 80% improvement in intra family connections. From the results it was observed that HHblits is more sensitive in detecting remote homologues compared to Master Blaster. However, there are true hits from 46-folds for which Master Blaster reported homologs that are not reported by HHblits even using the optimal parameters indicating that for detecting remote homologues, use of multiple methods employing a combination of different approaches can be more effective in detecting remote homologs. Master Blaster stand-alone code is available for download in the supplementary archive.


The development of stereoacuity in infant rhesus monkeys.
The emergence of stereopsis at 3-4 months postnatal in human infants is striking and has led to speculation that its rapid onset and subsequent development must be due to a dramatic reorganization of the brain. Stereopsis has never been measured in infant monkeys, but previous studies have demonstrated that many other visual functions develop four times faster in infant monkeys than in humans. We made longitudinal assessments of stereoacuity in 11 infant rhesus monkeys. A forced-choice preferential-looking technique was used to present random-dot stereograms during testing. By 8 weeks after birth, all of the monkeys were responding to at least coarse levels of disparity (1760" [seconds]), and by 13 weeks of age, all were responding to the relatively fine level of 88" disparity. Age of onset for stereopsis in monkeys was at about one-quarter the age when it occurs in humans, as expected. However, subsequent development proceeded at a similar absolute rate in monkeys and humans. The findings are discussed relative to the neural mechanisms which might be responsible for the differing rates of development.


Column elution and concentration of volatile compounds in biological fluids.
A new solvent elution method is described for the isolation and concentration of volatile metabolites in biological fluids. The procedure involves elution of the sample with a solvent through a micro-column of an adsorbent into glass-wool and evaporation of the excess solvent in a stream of helium at room temperature. The volatiles are revocered by subsequent heat desorption into a chromatogrpaphic system. Both elution and evaporation are made in a single step using a novel sampling device. Since the technique is based on liquid-solid adsorption chromatography, the adsorbent-solvent system which gives the maximum yield of volatile constituents was studied. The method is simple, highly efficient and reproducible, requiring only small volumes of biological fluids (less than 100 mul).


Antisecretory and antiulcer effect of T-330, a novel reversible proton pump inhibitor, in rats.
The antisecretory and antiulcer effects of T-330 (2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole) , a novel reversible proton pump inhibitor, were studied in rats. T-330 suppressed dibutyryl cyclic AMP-stimulated acid formation in isolated rat gastric mucosal cells with the IC50 value of 0.57 microM. In chronic fistula rats, intravenous, intraduodenal and oral administration of T-330 inhibited pentagastrin-stimulated gastric acid secretion; the ED50 values calculated from the peak inhibition were 0.36, 0.43 and 0.73 mg/kg, respectively. T-330 also reduced dimaprit-stimulated gastric acid secretion following its intraduodenal injection (ED50 0.85 mg/kg). The antisecretory activities of T-330 following its intraduodenal and oral administration were 3-6- and 4-10-times more potent than those of omeprazole and ranitidine, respectively, while the duration of action of T-330 was apparently shorter than that of omeprazole and was almost equal to that of ranitidine. Oral or duodenal administration of T-330 inhibited the development of acid-related damage (water-immersion- and aspirin-induced gastric lesions, cysteamine-induced duodenal ulcers and reflux esophagitis) with equal or higher potency than omeprazole or ranitidine. Furthermore, T-330 prevented ethanol-induced gastric lesions. These findings indicate that T-330 exerts its antiulcer effect mainly via its potent antisecretory action and partly via its gastroprotective action.


Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial.
Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, known as post-polio syndrome. Production of proinflammatory cytokines within the CNS indicates an underlying inflammatory process, accessible for immunomodulatory treatment. We did a multicentre, randomised, double-blind, placebo-controlled study of intravenous immunoglobulin in post-polio syndrome. 142 patients at four university clinics were randomly assigned infusion of either 90 g in total of intravenous immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days, repeated after 3 months. Seven patients were withdrawn from the study. Thus, 135 patients were assessed per protocol. Primary endpoints were muscle strength in a selected study muscle and quality of life as measured with the SF-36 questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk test (6MWT), timed up and go (TUG), muscle strength in muscles not chosen as the study muscle, physical activity scale of the elderly (PASE), visual analogue scale (VAS) for pain, multidimensional fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests were done immediately before the first infusion and 3 months after the second infusion. This study is registered with , number NCT00160082. Compared with baseline, median muscle strength differed by 8.3% between patients receiving intravenous immunoglobulin and placebo, in favour of the treatment group (p=0.029). SF-36 PCS did not differ significantly between the groups after treatment (p=0.321). Differences in the subscale vitality score (p=0.042) and PASE (p=0.018) favoured the active treatment group. MFI-20, TUG, muscle strength in the muscles not chosen as the study muscle, 6MWT, balance, and sleep quality did not differ between groups. For the whole study population there was no significant change in pain, as determined by VAS. Nevertheless, patients who reported pain at the study start improved in the intervention group but not in the placebo group (p=0.037). Intravenous immunoglobulin was well tolerated. Intravenous immunoglobulin could be a supportive treatment option for subgroups of patients with post-polio syndrome. Further studies on responding subgroups, long-term effects, and dosing schedules are needed.


Pulmonary neuroepithelial bodies as airway sensors: putative role in the generation of dyspnea.
The neuroepithelial bodies (NEB) of the intrapulmonary airways (AW) are multimodal AW sensors responding to a variety of stimuli including hypoxia, hypercarbia, and mechanical stretch. NEBs are richly innervated by a diverse population of mostly vagal afferent nerve fibers and owing to their early developmental maturation may be especially important during the perinatal period. This article reviews recent findings of NEB functional morphology and innervation, and postulates a role in the generation of dyspnea. This is based on their potential for transduction of dyspneic stimuli and findings of NEB cell abnormalities in a number of pulmonary disorders presenting with this symptom.


Tricuspid annular dilation in patients undergoing early mitral valve surgery: is it an old story?
Patients with mitral valve prolapse (MVP), undergoing early surgery for severe regurgitation, are usually characterized by a low degree of right chambers' remodeling. In this selected population, the mechanisms leading to tricuspid annular (TA) dilatation (TAD) are not well understood. In this setting, we aimed to evaluate, using three-dimensional echocardiography (3DE), how right chambers affect TA size and might contribute to functional tricuspid regurgitation (FTR) progression. We studied 159 patients treated with early isolated surgery for MVP, characterized by: sinus rhythm; normal biventricular function; normal or elevated pulmonary artery pressure; tricuspid regurgitation (TR) ≤ mild; no concomitant cardiac disease. All patients reached a 3-year echocardiographic follow-up. Based on two-dimensional echocardiography, patients were divided in Group 1 (N = 68, 43%, TAD, TA ≥ 21 mm/m2) and Group 2 (N = 91, 57%, no TAD, TA < 21 mm/m2). By 3DE, Group 1 showed larger TA size, right atrial (RA) volume and right ventricular (RV) conical remodeling compared to Group 2 (p < 0.05). The multivariate analysis revealed that RA volume, RV basal diameter and function were independently correlated to TA size (p < 0.05). At the 3-year follow-up there was a low incidence of FTR, with a trend towards FTR progression in Group 1 (p = 0.07). In patients undergoing early surgery for MVP, TAD seems to result from distinctive early-onset geometrical changes of the right chambers, preceding TR, RV dilatation and pulmonary hypertension at rest. An integrated approach, including right chambers' assessment by 3DE, might help to better recognized patients at higher risk for TAD and, potentially for FTR.


Sex and age differences in COVID-19 mortality in Europe.
To examine the magnitude of sex differences in survival from the coronavirus disease 2019 (COVID-19) in Europe across age groups and regions. We hypothesized that men have a higher mortality than women at any given age but that sex differences will decrease with age as only the healthiest men survive to older ages. We used population data from the Institut National D'Études Démographiques on cumulative deaths due to COVID-19 from February to June 2020 in 10 European regions: Denmark, Norway, Sweden, The Netherlands, England and Wales, France, Germany, Italy, Spain and Portugal. For each region, we calculated cumulative mortality rates stratified by age and sex and corresponding relative risks for men vs. women. The relative risk of dying from COVID-19 was higher for men than for women in almost all age groups in all regions. The overall relative risk ranged from 1.11 (95% confidence interval, CI 1.01-1.23) in Portugal to 1.54 (95% CI 1.49-1.58) in France. In most regions, sex differences increased until the ages of 60-69 years, but decreased thereafter with the smallest sex difference at age 80+ years. Despite variability in data collection and time coverage among regions, the study showed an overall similar pattern of sex differences in COVID-19 mortality in Europe.


Review of current knowledge of plastic intravenous fluid containers.
A review of the features of plastic intravenous fluid containers is presented. The following topics are discussed: (1) handling and storage; (2) environmental and human contamination; (3) particulate matter; (4) water vapor transmission; (5) drug additives; (6) leaching and adsorption; (7) possible toxicity; and (8) cost. It is concluded that various justifications can be presented for both glass and plastic containers.


Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues.
Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11-19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03-6.54, P < 0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P = 0.04) and BMI (HR/CI 1.11/1.03-1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.


The traditional herbal medicines mixture, Banhasasim-tang, relieves the symptoms of irritable bowel syndrome via modulation of TRPA1, NaV1.5 and NaV1.7 channels.
The cause of irritable bowel syndrome (IBS), a functional gastrointestinal (GI) disorder, remains unclear. Banhasasim-tang (BHSST), a traditional herbal medicines mixture, mainly used to treat GI-related diseases, may have a potential in IBS treatment. IBS is characterized by abdominal pain as the main clinical symptom, which seriously affects the quality of life. We conducted a study to evaluate the effectiveness of BHSST and its mechanisms of action in treating IBS. We evaluated the efficacy of BHSST in a zymosan-induced diarrhea-predominant animal model of IBS. Electrophysiological methods were used to confirm modulation of transient receptor potential (TRP) and voltage-gated Na+ (NaV) ion channels, which are associated mechanisms of action. Oral administration of BHSST decreased colon length, increased stool scores, and increased colon weight. Weight loss was also minimized without affecting food intake. In mice administered with BHSST, the mucosal thickness was suppressed, making it similar to that of normal mice, and the degree of tumor necrosis factor-α was severely reduced. These effects were similar to those of the anti-inflammatory drug-sulfasalazine-and antidepressant-amitriptyline. Moreover, pain-related behaviors were substantially reduced. Additionally, BHSST inhibited TRPA1, NaV1.5, and NaV1.7 ion channels associated with IBS-mediated visceral hypersensitivity. In summary, the findings suggest that BHSST has potential beneficial effects on IBS and diarrhea through the modulation of ion channels.


Pulmonary artery dopplers for early prediction of risk for bronchopulmonary dysplasia in extremely low birth weight babies.
The early abnormal pulmonary vasoreactivity observed in babies at risk of Bronchopulmonary dysplasia (BPD) increases the pulmonary vascular resistance. This can be assessed non-invasively using Time to Peak Velocity:Right Ventricular Ejection Time ratio (TPV:RVET) measured from pulmonary artery Doppler waveform obtained using echocardiogram. We postulate that screening for this early can predict BPD in this cohort. The objective of the study was to determine the utility of TPV:RVET in early prediction of BPD in Extremely Low Birth Weight (ELBW) babies born less than 1250grams Birth Weight. This was a single-center retrospective cohort study of ELBW babies born<29 weeks over 4 year period who had echocardiogram between 7-21 days of life. TPV:RVET ratio was measured from pulmonary artery Doppler waveform obtained using echocardiogram. The main outcome was BPD at 36 weeks corrected gestation. The predictive ability of TPV:RVET (cut off 0.34) for subsequent development of BPD was analyzed using ROC. Of 589 ELBW<29 weeks, 207 babies were eligible. BPD was found in 60.4%. The TPV:RVET at 0.34 had sensitivity 76.8% (95%CI 68.4-83.9), specificity 85.4% (95%CI 75.8-92.2), positive predictive value 88.9% (95%CI 81.4-94.1), negative predictive value 70.7% (95%CI 60.7-79), and ROC area 0.811 (95%CI 0.757-0.864). Odds ratio of having BPD for TPV:RVET at 0.34 was 19.9 (95%CI 8.19-48.34) and increased by 1.07 (95%CI 1.05-1.09) with every additional days of mechanical ventilation. TPV:RVET ratio had 92.75% inter-observer agreement with kappa 0.83. TPV:RVET ratio is a good and reliable early screening tool for subsequent development of BPD in ELBW babies with substantial inter-observer agreement.


GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration.
Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma characterized by high aggressiveness and extremely poor patient prognosis. The germ cell‑specific gene 2 protein (GSG2) is a histone H3 threonine‑3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in the progression and development of CCA remain elusive. In the present study, the association between GSG2 and CCA was elucidated. Firstly, we demonstrated that GSG2 was overexpressed in CCA specimens and HCCC‑9810 and QBC939 cells by immunohistochemical (IHC) staining. It was further revealed that high expression of GSG2 in CCA had significant clinical significance in predicting disease deterioration. Subsequently, cell proliferation, apoptosis, cell cycle distribution and migration were measured by MTT, flow cytometry, and wound healing assays, respectively in vitro. The results demonstrated that downregulation of GSG2 decreased proliferation, promoted apoptosis, arrested the cell cycle and weakened migration in the G2 phase of CCA cells. Additionally, GSG2 knockdown inhibited CCA cell migration by suppressing epithelial‑mesenchymal transition (EMT)‑related proteins, such as N‑cadherin and vimentin. Mechanistically, GSG2 exerted effects on CCA cells by modulating the PI3K/Akt, CCND1/CDK6 and MAPK9 signaling pathways. In vivo experiments further demonstrated that GSG2 knockdown suppressed tumor growth. In summary, GSG2 was involved in the progression of CCA, suggesting that GSG2 may be a potential therapeutic target for CCA patients.


Skin avulsion during oscillometry.
We observed a case of skin avulsion associated with measurement of blood pressure by oscillometry on an anesthetized patient in the prone position. Epidermal shearing may be avoided in the prone patient by either wrapping the antecubital skin underlying the blood pressure cuff with gauze or preventing weight-bearing by the cuffed portion of the arm.


Challenges in Tracking and Reporting Antibiotic Use in Long-Term Care.
The contemporary long-term care provider and interdisciplinary team are well aware of the recent focus on antibiotic use in their settings. Regulatory changes implemented by Centers for Medicare and Medicaid Services beginning in 2016 have required long-term care settings to look at antibiotic use in a more comprehensive way and to align their programs with the Centers for Disease Control and Prevention's Core Elements for Antibiotic Stewardship for Nursing Homes. As long-term care settings have worked to develop antibiotic stewardship programs over the past several years, there have been many discoveries about the processes involved in gathering data about antibiotic use and associated attributes, including dose, duration of therapy, and indication for use. Attempts to align these attributes with appropriateness may require integration of data elements from pharmacy records and the individual resident's electronic medical record. In this article, we systematically discuss relevant antibiotic use metrics, sources of antibiotic use data, collecting and reporting antibiotic use data, concluding with implications for policy, practice, and research. Only by measuring antibiotic use can we start to assess the effectiveness of antibiotic stewardship program to induce meaningful change in the care of residents in long-term care.


A Local Strategy Toward Concurrent Chemoradiotherapy Based on Fibrin Gel for Postsurgical Cancer Treatment.
Postoperative cancer recurrence and metastasis have always been huge challenges in cancer therapy. The concurrent cisplatin (CDDP)-based chemoradiotherapy regimen is a standard therapeutic strategy in some cancer treatments after surgical resection. However, severe side effects and unsatisfactory local tumor concentrations of CDDP have hampered the application of this concurrent chemoradiotherapy. Therefore, a superior option that can enhance CDDP-based chemoradiotherapy efficacy with milder concurrent therapy-related toxicity is highly desirable. We developed a platform based on fibrin gel (Fgel) loaded with CDDP to be implanted into the tumor bed after surgery combined with concurrent radiation therapy for the prevention of postoperative local cancer recurrence and distant metastasis. The postoperative subcutaneous tumor mouse models established by incomplete resection of primary tumors were used to evaluate the therapeutic advantages of this chemoradiotherapy regimen for postsurgical treatment. The local and sustained release of CDDP from Fgel could enhance the antitumor efficacy of radiation therapy in the residual tumor with lower systemic toxicity. The therapeutic benefits of this approach are demonstrated in breast cancer, anaplastic thyroid carcinoma, and osteosarcoma mouse models. Our work offers a general platform for concurrent chemoradiotherapy to prevent postoperative cancer recurrence and metastasis.


Unilateral cystoid macular edema and bilateral subfoveal hyperreflectivity following docetaxel chemotherapy: A case report.
To report the findings of unilateral cystoid macular edema (CME) associated with bilateral sub-foveal hyperreflectivity in a patient previously diagnosed with breast cancer and treated with docetaxel and cyclophosphamide. A 69-year-old female on docetaxel and cyclophosphamide chemotherapy treatment for breast cancer developed blurry vision 20 days after initiation of therapy. Ophthalmic examination revealed reduced visual acuity with bilateral retinal pigment epithelium mottling and annular sub-foveal thickening in the left eye. Optical coherence tomography (OCT) showed cystoid macular changes in the right eye and central sub-macular hyperreflectivity of outer layers in both eyes. Six-months after discontinuation of therapy, OCT findings remained unchanged and visual acuity did not improve. CME may occur in patients taking taxanes, but this finding associated with sub-macular hyperreflectivity of the outer layers in diagnostic testing has never been reported before. Sub-macular deposits found in this patient may be responsible for decreased vision and did not respond to cessation of therapy.


Interrole conflict and self-efficacy to manage work and family demands mediate the relationships of job and family demands with stress in the job and family domains.
This study derives from Work-Home Resources model (ten Brummelhuis, L. L., & Bakker, A. B. (2012). A resource perspective on the work-home interface: The work-home resources model. American Psychologist, 67(7), 545-556. doi: 10.1037/a0027974 ) and Social Cognitive Theory (Bandura, A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ, US: Prentice-Hall, Inc.) to investigate mechanisms responsible for the effect of job and family demands on work- and family-related perceived stress. We hypothesized that interrole conflict and self-efficacy to manage work and family demands operate either independently or sequentially transmitting the effects of demands on perceived stress. A sample of 100 employees of various occupations participated in the study conducted online in two waves: Time 1 (T1) and Time 2 (T2) with a three-month interval. Regression analysis with bootstrapping was applied. Interrole conflict (T1) did not mediate the relationships between demands (T1) and perceived stress (T2), whereas self-efficacy (T1) mediated only those between family demands (T1) and stress (T2). However, data supported the sequential mediation hypotheses: Demands (T1) were associated with increased interrole conflict (T1) which in turn decreased self-efficacy (T1) and ultimately resulted in the elevated perceived stress at work and in the family (T2). Demands originating in one domain can impact stress both in the same and other life areas through the sequence of interrole conflict and context-specific self-efficacy.


Middle ear impedance studies in elderly patients implications on age-related hearing loss.
Controversies arise with respect to functioning of the middle ear over time. To assess changes in middle ear impedance that may be related to aging, and/or if there was an association of these changes with those of the inner ear in the elderly patients. Cross-sectional, comparative study of elderly patients managed in ear, nose and throat clinics. A structured questionnaire was administered to obtain clinical information. Pure tone audiometry, tympanometry, and acoustic reflexes were performed. Comparative analyses were performed to detect intergroup differences between clinico-audiometric findings and middle ear measures, viz. tympanograms and acoustic reflexes. One hundred and three elderly patients participated in the study; 52.4% were male, averagely 70.0±6.3 years old, age-related hearing loss in 59.2%, abnormal tympanograms in 39.3%, absent acoustic reflex in 37.9%. There was no association between age and gender in patients with abnormal tympanograms and absent acoustic reflex. Significantly more patients with different forms and grades of age-related hearing loss had abnormal tympanometry and absent acoustic reflex. Some abnormalities were observed in the impedance audiometric measures of elderly patients, which were significantly associated with parameters connected to age-related hearing loss.


Solo single incision laparoscopic S8 non-anatomical resection and left lateral sectionectomy.
Highlight Jung and colleagues demonstrated the feasibility of single-port laparoscopic multiple liver resection using the lift-up technique and the parallel method. In this video they present their technique, indicating the new possibility of hepatectomy using the ordinary skills of laparoscopic hepatectomy through a single port.


SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway.
Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.


Coding for Physical Restraint Status Among Hospitalized Patients: a 2019 National Inpatient Sample Analysis.
The reduction of physical restraint utilization in the hospital setting is a key goal of high-quality care, but little is known about the rate of restraint use in general hospitals in the USA. This study reports the rate of physical restraint coding among acute care hospital discharges in the USA and explores associated demographic and diagnostic factors. The National Inpatient Sample, a de-identified all-payors database of acute care hospital discharges in the USA, was queried for patients aged 18 and older with a diagnosis code for physical restraint status in 2019. Hospitalized patients aged 18 and older. Demographics, discharge diagnoses, in-hospital mortality, length of stay, total hospital charges. In total, 220,470 (95% CI: 208,114 to 232,826) hospitalizations, or 0.7% of overall hospitalizations, included a discharge code for physical restraint status. There was a 700-fold difference in coding for restraint utilization based on diagnosis, with 7.4% of patients with encephalitis receiving restraint diagnosis codes compared to < 0.01% of patients with uncomplicated diabetes. In an adjusted model, male sex was associated with an odds ratio of 1.4 (95% CI: 1.4 to 1.5) for restraint utilization coding, and Black race was associated with an odds ratio of 1.3 (95% CI: 1.2 to 1.4) relative to white race. In the general hospital setting, there is variability in physical restraint coding by sex, race, and clinical diagnosis. More research is needed into the appropriate utilization of restraints in the hospital setting and possible inequities in restraint utilization.


NMR-spectroscopic analysis of mixtures: from structure to function.
NMR spectroscopy as a particularly information-rich method offers unique opportunities for improving the structural and functional characterization of metabolomes, which will be essential for advancing the understanding of many biological processes. Whereas traditionally NMR spectroscopy was mostly relegated to the characterization of pure compounds, the past few years have seen a surge of interest in using NMR-spectroscopic techniques for characterizing complex metabolite mixtures. Development of new methods was motivated partly by the realization that using NMR for the analysis of metabolite mixtures can help identify otherwise inaccessible small molecules, for example compounds that are prone to chemical decomposition and thus cannot be isolated. Furthermore, comparative metabolomics and statistical analyses of NMR spectra have proven highly effective at identifying novel and known metabolites that correlate with changes in genotype or phenotype. In this review, we provide an overview of the range of NMR-spectroscopic techniques recently developed for characterizing metabolite mixtures, including methods used in discovery-oriented natural product chemistry, in the study of metabolite biosynthesis and function, or for comparative analyses of entire metabolomes.


Bioactive clerodane diterpenes of giant goldenrod (Solidago gigantea Ait.) root extract.
Giant goldenrod (Solidago gigantea Ait.) root extract was screened for bioactive compounds by high-performance thin-layer chromatography (HPTLC), coupled with effect-directed analysis including antibacterial (Bacillus subtilis F1276, B. subtilis subsp. spizizenii, Aliivibrio fischeri and Xanthomonas euvesicatoria), antifungal (Fusarium avenaceum) and enzyme inhibition (acetyl- and butyrylcholinesterases, α- and β-glucosidases and α-amylase) assays. Compounds of six multipotent zones (Sg1-Sg6) were characterized by HPTLC-heated electrospray ionization-high-resolution mass spectrometry (HRMS) and HPTLC-Direct Analysis in Real Time-HRMS. Apart from zone Sg3, containing three compounds, a single characteristic compound was detectable in each bioactive zone. The bioassay-guided isolation using preparative-scale flash chromatography and high-performance liquid chromatography provided eight compounds that were identified by NMR spectroscopy as clerodane diterpenes. All isolates possessed inhibiting activity against at least one of the tested microorganisms.


The impact of Aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer.
Cancer stem cells may be associated with tumor progression and prognosis for colon cancer. We hypothesized that expression of Aldehyde dehydrogenase 1 (ALDH1) would increase with tumor progression and be associated with survival. Tissue was obtained from resection specimens for isolation of cancer stem cells. In addition, paraffin blocks from resected colon cancers with normal colon, primary tumor, and lymph node and liver metastasis from 2000 to 2010 were identified and stained with ALDH1. In in vitro models (adherent and tumor spheres) ALHD1+ cells grew more efficiently than ALDH1- cells. ALDH1 expression was highest in peritumoral crypt cells (0.137 μm(2), 95% confidence interval [CI] 0.125-0.356) and normal crypts (median 0.091 μm(2), 95% CI 0.064-0.299) followed by lymph node metastasis (median 0.025 μm(2), 95% CI 0-0.131) and the primary cancers (median 0.014 μm(2), 95% CI 0.0123-0.154). Samples were divided into high and low ALDH1 expression. Survival was associated with expression in the primary tumor (9 versus 23 mo, P = 0.0016) expression but not peritumoral tissue (21 versus 20.5 mo, P = 0.32), normal colon (19 versus 27 mo, P = 0.289), or lymph node metastasis (23 versus 21 mo, P = 0.69). On univariate analysis, ALDH1 expression and grade were associated with survival but ages, number of lymph node metastasis, race, or grade were not associated. On multivariate analysis, only ALDH1 status continued to be associated with survival, odds ratio 4.4, and P = 0.011. ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. Expression did not increase with progression from normal colon to primary tumors and metastasis.


DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH.
Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.


The association of pre-eclampsia with the Duffy negative phenotype in women of West African descent.
To investigate whether pre-eclampsia in Curaçao is associated with the Duffy negative phenotype. Retrospective study. Women with a history of pre-eclampsia had a higher Duffy negative phenotype frequency compared with women with a history of uncomplicated pregnancies (52.8 vs 27.3%, respectively; odds ratio 2.98; 95% CI 1.40-6.32; P = 0.004). Pre-eclampsia is associated with the Duffy negative phenotype in women of West-African descent in the island of Curaçao.


Multidimensional Characterization of Single-Molecule Dynamics in a Plasmonic Nanocavity.
Nanoscale manipulation and characterization of individual molecules is necessary to understand the intricacies of molecular structure, which governs phenomena such as reaction mechanisms, catalysis, local effective temperatures, surface interactions, and charge transport. Here we utilize Raman enhancement between two nanostructured electrodes in combination with direct charge transport measurements to allow for simultaneous characterization of the electrical, optical, and mechanical properties of a single molecule. This multi-dimensional information yields repeatable, self-consistent, verification of single-molecule resolution, and allows for detailed analysis of structural and configurational changes of the molecule in situ. These experimental results are supported by a machine-learning based statistical analysis of the spectral information and calculations to provide insight into the correlation between structural changes in a single-molecule and its charge-transport properties.


Hospital volume is associated with cost and outcomes variation in 2,942 pelvic reconstructions.
Complex pelvic reconstruction is challenging for plastic and reconstructive surgeons following surgical resection of the lower gastrointestinal or genitourinary tract. Complication rates and hospital costs are variable and may be linked to the hospital case volume of pelvic reconstructions performed. A comprehensive examination of these factors has yet to be performed. Data were retrieved for patients undergoing pedicled flap reconstruction after pelvic resections in the American National Inpatient Sample database between 2010 and 2014. Patients were then separated into three groups based on hospital case volume for pelvic reconstruction. Multivariate logistic regression and gamma regression with log-link function were used to analyze associations between hospital case volume, surgical outcomes, and cost. In total, 2,942 patients underwent pelvic flap reconstruction with surgical complications occurring in 1,466 patients (49.8%). Total median cost was $38,469.40. Pelvic reconstructions performed at high-volume hospitals were significantly associated with fewer surgical complications (low: 51.4%, medium: 52.8%, high: 34.8%; p < 0.001) and increased costs (low: $35,645.14, medium: $38,714.92, high: $44,967.29; p < 0.001). After regression adjustment, high hospital volume was the strongest independently associated factor for decreased surgical complications (Exp[β], 0.454; 95% Confidence Interval, 0.346-0.596; p < 0.001) and increased hospital cost (Exp[β], 1.351; 95% Confidence Interval, 1.285-1.421; p < 0.001). Patients undergoing pelvic flap reconstruction after oncologic resections experience high complication rates. High case volume hospitals were independently associated with significantly fewer surgical complications but increased hospital costs. Reconstructive surgeons may approach these challenging patients with greater awareness of these associations to improve outcomes and address cost drivers.


Surface ultrastructure of the gill arch of the killifish, Fundulus heteroclitus, from seawater and freshwater, with special reference to the morphology of apical crypts of chloride cells.
The surface ultrastructure of the gill arches of the killifish, Fundulus heteroclitus, adapted to seawater or freshwater, was found to be similar to that reported for other euryhaline teleosts. Two rows of gill filaments (about 42 filaments per row) extended posterolaterally, and two rows of gill rakers (about 10 rakers per row) extended anteromedially from each arch. Leaf-like respiratory lamellae protruded along both sides of each filament, from its base to its apex. The distributions, sizes, and numbers of various surface cells and structures were also determined. All surfaces were covered by a mosaic of pavement cells, which measured about 7 X 4 microns and exhibited concentrically arranged surface ridges. Taste buds were especially prominent on the rakers and the pharyngeal surfaces of the first and second gill arches, but were often replaced by horny spines on the third and fourth gill arches. Apical crypts of chloride cells occurred mostly on the surfaces of the gill filaments adjacent to the afferent artery of the filament. In seawater adapted killifish, crypts resembled narrow, deep holes along the borders of adjacent pavement cells, had openings of about 2 microns2, and occurred at a frequency of about 1 per 70 microns2 of surface area. In freshwater fish, the crypts usually had larger openings (about 10 microns2), occurred less frequently (1 per 123 microns2), and exhibited many cellular projections in their interiors. Changes in crypt morphology may be related to the ion transport function of chloride cells.


An examination of exposure measurement error from air pollutant spatial variability in time-series studies.
Relatively few studies have evaluated the effects of heterogeneous spatiotemporal pollutant distributions on health risk estimates in time-series analyses that use data from a central monitor to assign exposures. We present a method for examining the effects of exposure measurement error relating to spatiotemporal variability in ambient air pollutant concentrations on air pollution health risk estimates in a daily time-series analysis of emergency department visits in Atlanta, Georgia. We used Poisson generalized linear models to estimate associations between current-day pollutant concentrations and circulatory emergency department visits for the 1998-2004 time period. Data from monitoring sites located in different geographical regions of the study area and at different distances from several urban geographical subpopulations served as alternative measures of exposure. We observed associations for spatially heterogeneous pollutants (CO and NO(2)) using data from several different urban monitoring sites. These associations were not observed when using data from the most rural site, located 38 miles from the city center. In contrast, associations for spatially homogeneous pollutants (O(3) and PM(2.5)) were similar, regardless of the monitoring site location. We found that monitoring site location and the distance of a monitoring site to a population of interest did not meaningfully affect estimated associations for any pollutant when using data from urban sites located within 20 miles from the population center under study. However, for CO and NO(2), these factors were important when using data from rural sites located > or = 30 miles from the population center, most likely owing to exposure measurement error. Overall, our findings lend support to the use of pollutant data from urban central sites to assess population exposures within geographically dispersed study populations in Atlanta and similar cities.


Role of oxygen reactive species in Schistosoma mansoni egg-induced granulomatous inflammation.
The role of oxygen reactive species in granulomatous hypersensitivity was explored using a model of pulmonary granulomas induced by intravenous injection of eggs from the parasite Schistosoma mansoni. Macrophages from sychronously developing lesions spontaneously released significant quantities of superoxide anion (26 nmoles/10(6)/2h) by 8 days of development. In contrast, the non-T cell foreign body (Sephadex bead) granuloma macrophages produced only (2 nmoles/10(6)/2h) small quantities. Daily administration of the oxygen scavenger, alpha-tocopherol, by either oral or parenteral routes caused up to 60% suppression of granuloma size. Moreover, parenteral administration of specific inactivators of 0-2 and H2O2, superoxide dismutase and catalase respectively, resulted in a 30 to 40% reduction in granuloma size. These data suggest that oxygen reactive species take part in the generation of hypersensitivity granulomas.


Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.
There is a robust association between altered angiogenic factor concentrations, which includes placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women with suspected preeclampsia at <35 weeks gestation, however, remains to be clarified. The purposes of this study were to examine the relationship between placental growth factor and time to delivery in women at <35 weeks gestation with signs or symptoms of preeclampsia and to compare the performance of placental growth factor to other clinical markers for prediction of time to delivery in preeclampsia. Women with signs or symptoms of preeclampsia between 20.0 and 35.0 weeks gestation were enrolled in a prospective, observational study at 24 centers. Blood was collected at presentation for placental growth factor, and subjects were evaluated and treated according to local protocols. Clinical outcomes were obtained, and all final diagnoses were adjudicated by an independent expert panel according to 2013 American College of Obstetricians and Gynecologists' Hypertension in Pregnancy criteria. Placental growth factor was measured retrospectively on the Alere, Inc, triage platform. A normal placental growth factor was defined as >100 pg/mL; the assay's limit of detection is 12 pg/mL. Two-by-2 tables were constructed for comparison of test outcomes that included negative predictive value; time-to-delivery was analyzed by survival curves and Cox regression. Seven hundred fifty-three subjects were enrolled; 538 (71%) had a final diagnosis of preeclampsia; 542 (72%) delivered at <37 weeks gestation, and 358 (47%) delivered at <34 weeks gestation. Among the 279 women (37%) with a normal placental growth factor at presentation, the negative predictive value for preeclampsia delivered within 14 days or within 7 days was 90% and 93%, respectively. Compared with women with normal placental growth factor, women with placental growth factor ≤100 pg/mL have a hazard ratio of 7.17 (confidence interval, 5.08-10.13) in Cox regression for time to delivery after adjustment for both gestational age at enrollment and the final diagnosis of preeclampsia. The placental growth factor levels of normal (>100 pg/mL), low (12-100 pg/mL), and very low (<12 pg/mL) have well-separated distributions of time to delivery, with median values of 45, 10, and 2 days, respectively. Subjects with placental growth factor ≤100 pg/mL have a perinatal death rate of 5.7% and a small-for-gestational-age rate of 51.7%; subjects with placental growth factor >100 pg/mL have a perinatal death rate of 0% (no observations in this cohort) and an a small-for-gestational-age rate of 16.8%. In women with suspected preeclampsia at <35.0 weeks gestation, a low placental growth factor was correlated strongly with preterm delivery independent of a diagnosis of preeclampsia or gestational age at presentation, whereas a normal placental growth factor was associated with pregnancy prolongation, even in patients who ultimately had a final diagnosis of preeclampsia. This suggests that placental growth factor levels are superior to clinical markers in the prediction of adverse pregnancy in women with suspected preeclampsia.


Effect of chlorhexidine and acetic acid on phagocytosis by polymorphonuclear leucocytes.
The effect of two disinfectants, chlorhexidine and acetic acid, on host leucocytes and bacteria was studied. At a concentration of 50 mg/l, chlorhexidine was found to be bactericidal without interfering with leucocyte function. A concentration of 500 mg/l of acetic acid was neither leucotoxic nor bactericidal. Effects equivalent to the aforementioned were achieved in serum by increasing the chlorhexidine concentration by a factor of 20 and the acetic acid concentration by a factor of 5. Acetic acid reduced leucocyte function more rapidly than it killed bacteria. On the basis of these findings, chlorhexidine is to be preferred for local application in burn wounds to prevent colonisation and infection.


Can we increase smokers' adherence to nicotine replacement therapy and does this help them quit?
To examine the effects of five intervention components on smokers' adherence to combined nicotine patch and nicotine gum during a quit attempt and assess whether adherence is related to cessation. Smokers interested in quitting (N = 513; 59% female; 87% White) received nicotine patch plus nicotine gum and participated in a 2x2x2x2x2 randomized factorial experiment (i.e., 32 treatment conditions) evaluating five intervention components: (1) medication adherence counseling versus none; (2) automated medication adherence calls versus none; (3) electronic medication monitoring with feedback and counseling versus e-monitoring alone; (4) 26 versus 8 weeks of nicotine patch plus nicotine gum; and (5) maintenance counseling versus none. Adherence was assessed over the first 6 weeks post-target quit day via timeline follow-back (nicotine patch) and electronic medication dispenser (gum). In the first 6 weeks post-quit day, 12% of participants used no patches or gum, and 40% used the patch every day. Only 1.4% used both patch and gum adherently every day in the 6 weeks post-target quit day. E-monitoring counseling increased gum use (from 1.9 to 2.6 pieces/day; p < .001) but did not increase abstinence. More adherent patch and gum use in the first 6 weeks were each associated with higher point-prevalence abstinence rates through 1 year. This large experiment with electronic monitoring of nicotine gum adherence showed that e-monitoring counseling increased gum use but not abstinence. Adherence to nicotine patch and to gum were each strongly related to abstinence, but it is unclear whether adherence increases abstinence, or relapse causes medication discontinuation. ClinicalTrials.gov NCT01120704.


Beam shaping and probe characterization in the scanning electron microscope.
Here we demonstrate the use of nanofabricated grating holograms to diffract and shape electrons in a scanning electron microscope. The diffraction grating is placed in an aperture in the column. The entire diffraction pattern can be passed through the objective lens and projected onto the specimen, or an intermediate aperture can be used to select particular diffracted beams. We discuss several techniques for characterizing the diffraction pattern. The grating designs can incorporate features that can influence the phase and intensity of the diffracted SEM probe. We demonstrate this by producing electron vortex beams.


Handgrip strength is associated with insulin resistance and glucose metabolism in adolescents: Evidence from National Health and Nutrition Examination Survey 2011 to 2014.
Previous studies have reported that handgrip strength, a measure of muscular fitness, is associated with insulin resistance in children and adolescents, with conflicting results. Further, no studies have examined the association between handgrip strength with 2-hour glucose levels. We tested the association of handgrip strength with measures of insulin resistance (fasting insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) and glucose metabolism (fasting and 2-hour glucose levels) in adolescents from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. The study included 959 participants aged 12 to 19 years who underwent a handgrip test and a glucose tolerance test. General linear models were used to examine the associations between handgrip strength and the outcome variables. After adjustment for age, race, sex, body mass index, and physical activities, handgrip strength was inversely associated with fasting insulin levels (P = .017) and HOMA-IR (P = .025). Although there was no association between handgrip strength and fasting glucose levels (P = .77), handgrip strength was inversely associated with 2-hour glucose levels (P < .0001). Insulin and 2-hour glucose levels decreased linearly as handgrip strength increased from the bottom quartile to the top quartile (P for trend: .045 for fasting insulin levels and .004 for 2-hour glucose levels). Muscular fitness, measured by handgrip strength, is associated with insulin resistance and glucose metabolism in adolescents, which indicates that increasing muscular fitness may have beneficial effects for early prevention of insulin resistance and type 2 diabetes.


Decellularized Cryopreserved Allografts as Off-the-Shelf Allogeneic Alternative for Heart Valve Replacement: In Vitro Assessment Before Clinical Translation.
Cryopreserved allogeneic conduits are the elective biocompatible choice among currently available substitutes for surgical replacement in end-stage valvulopathy. However, degeneration occurs in 15 years in adults or faster in children, due to recipient's immunological reactions to donor's antigens. Here, human aortic valves were decellularized by TRICOL, based on Triton X-100 and sodium cholate, and submitted to standard cryopreservation (TRICOL-human aortic valves (hAVs)). Tissue samples were analyzed to study the effects of the combined procedure on original valve architecture and donor's cell removal. Residual amounts of nucleic acids, pathological microorganisms, and detergents were also investigated. TRICOL-hAVs proved to be efficaciously decellularized with removal of donor's cell components and preservation of valve scaffolding. Trivial traces of detergents, no cytotoxicity, and abrogated bioburden were documented. TRICOL-hAVs may represent off-the-shelf alternatives for both aortic and pulmonary valve replacements in pediatric and grown-up with congenital heart disease patients.


Clinical research of insulin glargine U300 in type 1 diabetes mellitus patients with frequent hypoglycaemia: real-world experience.
We aimed to see whether insulin glargine U300 can provide better blood glucose control while reducing hypoglycaemia in a more homogeneous population compared to previous studies. The retrospective study included type 1 diabetes mellitus (T1DM) patients with frequent hypoglycaemia. For evaluation of fasting blood glucose, haemoglobin glycated (HbA1c) and weight at 6 months and 12 months (final), observation windows of 120-240 days (4-8 months) and 240-480 days (9-16 months) after insulin glargine U300 initiation, respectively, were permitted. Mean follow-up time was 12 months. Hypoglycaemia was defined as blood glucose level < 70 mg/dl, either symptomatic or asymptomatic, measured in hospital or at home. Forty-four patients were included in the study, and 35 patients completed the study - 20 (57.1%) females and 15 (42.9%) males, with a mean age of 24.1 ±6.6 years. Mean body mass index was 24.4 ±7.4 kg/m2. A significant decrease was not found between baseline and HbA1c values at 6 months (p = 0.199), but a significant decrease was found in the final period (between 9-16 months) (p = 0.025). Hypoglycaemic events occurred in all patients (100%) before using insulin glargine U300, while the incidence of hypoglycaemic events gradually decreased to 74.3%, 68.6%, and 68.6% between months 1-3, 3-6, and 6-9, respectively. Of the 26 patients who declared their level of satisfaction, 23 (88.5%) were satisfied, 2 (7.7%) indicated that there was no significant difference, and 1 (3.8%) patient was unsatisfied. Over 9-16 months of follow-up, insulin glargine U300 led to a significant reduction not only of HbA1c levels but also of the frequency of hypoglycaemia, and also yielded high satisfaction rates.