[The assay of intracelluar cytidine deaminase activity and its clinical significance in patient with acute leukemia].
To investigate the relationship between the intracellular cytidine deaminase (CDD) activity and drug resistance in acute leukemia (AL) of different stage. CDD activity of 80 AL patients was determined by radioactive isotope assay. CDD activity of previously untreated and refractory/relapse AL patients was much higher than that of patients in complete remission (P<0.05). There was no significant difference of CDD activity between previously untreated and refractory/relapse patients (P>0.05). The activity of CDD had no correlation with age, sex, classification of AL and effect of chemotherapy containing cytidine deaminase (Ara-C). Intracellular CDD activity in AL patients may be related to the stages of the disease. It seemed that CDD might not be considered as an independent predictive factor for the drug healing efficacy of Ara-C.


Glycosylation of mouse embryonic hemoglobins in cultured yolk sac erythroblasts.
Embryonic hemoglobins of yolk sac nucleated erythroblasts were glycosylated in vitro by (3H)-glucose and the rate of glycosylation was maximal within 24 h of incubation. Isoelectric focusing of the glycosylated products revealed that both EI and EII embryonic hemoglobins have glycosylated components, EIg, EIIg, with pI very close to the native hemoglobins.


Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.
Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.


Cholestatic liver disease masquerading as Wilson disease.
Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.


Perceptions of Parents' Mental Health and Perceived Stigma by Refugee Youth in the U.S. Context.
Refugees are at an increased risk of mental health problems due to the multiple traumas experienced. Mental health help-seeking and utilization remains low among resettled refugees in the US, however, with stigma as a major barrier. The goal of this paper was to explore second-generation youth's perceptions of parents' mental health and perceived stigma. Data includes in-depth interviews with 62 Bosnian youth resettled in St. Louis. Results indicate that from the perspective of their children, first-generation refugee parents continue to face mental health challenges. The findings show that parents' and youth's understanding of mental health is tied to cultural stigma surrounding mental health. Additionally, intergenerational trauma might be affecting the child-parent relationship. As mass violence around the world continues and people are at continued risk of becoming refugees, this study contributes by advancing research on the long-term mental health and well-being of refugees and their children.


3D computational model of oxygen depletion kinetics in brain vasculature during FLASH RT and its implications for in vivo oximetry experiments.
Ultra-high-dose-rate irradiation, also known as FLASH, has been shown to improve the therapeutic ratio of radiation therapy (RT). The mechanism behind this effect has been partially explained by the radiochemical oxygen depletion (ROD) hypothesis, which attributes the protection of the normal tissue to the induction of transient hypoxia by ROD. To better understand the contribution of oxygen to the FLASH effect, it is necessary to measure oxygen (O2 ) in vivo during FLASH irradiation. This study's goal is to determine the temporal resolution required to accurately measure the rapidly changing oxygen concentration immediately after FLASH irradiation. We conducted a computational simulation of oxygen dynamics using a real vascular model that was constructed from a public fluorescence microscopy dataset. The dynamic distribution of oxygen tension (po2 ) during and after FLASH RT was modeled by a partial differential equation (PDE) considering oxygen diffusion, metabolism, and ROD. The underestimation of ROD due to oxygen recovery was evaluated assuming either complete or partial depletion, and a range of possible values for parameters such as oxygen diffusion, consumption, vascular po2 and vessel density. The O2 concentration recovers rapidly after FLASH RT. Assuming a temporal resolution of 0.5 s, the estimated ROD is only 50.7% and 36.7% of its actual value in cases of partial and complete depletion, respectively. Additionally, the underestimation of ROD is highly dependent on the vascular density. To estimate ROD rate with 90% accuracy, temporal resolution on the order of milliseconds is required considering the uncertainty in parameters involved, especially, the diverse vascular density of the tissue. The rapid recovery of O2 poses a great challenge for in vivo ROD measurements during FLASH RT. Temporal resolution on the order of milliseconds is recommended for ROD measurements in the normal tissue. Further work is warranted to investigate whether the same requirements apply to tumors, given their irregular vasculature.


The somatostatin analogue SOM230, compared with octreotide, induces differential effects in several metabolic pathways in acromegalic patients.
Recently, our first clinical study with the novel multiligand somatostatin (SRIF) analogue SOM230 in acromegalic patients showed that SOM230, due to its beneficial inhibitory effects on GH levels compared with octreotide (OCT), might increase the number of patients that can be biochemically controlled. Since SRIF analogues are also known to interact with other metabolic pathways, IGF-I, IGFBP-1, glucose and insulin concentrations on the control day (CD) and on treatment days following a single s.c. injection SOM230 100 and 250 microg, were compared to those following OCT 100 microg. Randomized, cross-over, double-blinded proof-of-concept trial in 12 patients with active acromegaly. Free IGF-I levels were suppressed after 24 h by OCT, SOM230 250 and 100 microg, whereas at 48 h only both SOM230 dosages still induced these inhibitory effects. Circulating IGFBP-1 levels (AUC; 0830-1430 h) compared with CD, increased sharply after OCT (from 48 to 237 microg/l/h; P < 0.001 vs. CD), while SOM230 250 and 100 microg elicited a lower and dose-dependent effect (163 and 90 microg/l/h, respectively, P < 0.05 vs. CD and OCT). Neither insulin nor GH levels showed statistically significant correlation with IGFBP-1 levels either after SOM230 or OCT. An early rise in glucose levels 1 h postinjection with SOM230 250 microg compared with OCT and CD was observed 8.3 +/- 0.8, 4.4 +/- 0.5 and 4.9 +/- 0.4 mmol/l, respectively: P < 0.05). SOM230 250 microg (19 +/- 4 vs. 46 +/- 3 mU/l on CD: P < 0.05), although clearly less potent than OCT (5.4 +/- 0.4 mU/l: P < 0.01 vs. CD), inhibited insulin release. Since these corresponding absolute insulin levels cannot entirely explain this hyperglycaemic effect of SOM230, other mechanisms seem involved in this glucose rise. If SOM230 would influence glucose homeostasis in peripheral target tissues of insulin action, expression of SS-receptors (sst) seems a logical necessity. In normal human liver tissues, analysed by quantitative polymerase chain reaction (PCR), the average sst1 mRNA expression level appeared significantly higher compared with sst2 (n = 6, relative copy number 161 +/- 46 vs. 57 +/- 6; P < 0.05). Fat tissue expressed both sst1 and sst2 mRNA, whereas in muscle only sst2 mRNA was found. Both dosages of SOM230 inhibit free IGF-I in a more sustained fashion compared to OCT, implying longer duration of action. The superior action of OCT compared with SOM230 in stimulating IGFBP-1 levels, suggests direct regulation of IGFBP-1 by SRIF analogues via sst2. Finally, expression of only sst1 and sst2 in target tissues of insulin action, might point towards additional modulatory effects by SOM230 on glucose homeostasis.


Compromised DNA damage repair promotes genetic instability of the genomic magnetosome island in Magnetospirillum magneticum AMB-1.
Magnetotactic bacteria (MTB) are capable of synthesizing nano-sized, intracellular membrane-bound magnetosomes. To learn more about the genetic factors involved in magnetosome formation, transposon mutagenesis was carried out by conjugation using a hyperactive mariner transposon to obtain nonmagnetic mutants of Magnetospirillum magneticum AMB-1. A mutant with defect in uvrA gene encoding the DNA binding subunit of the UvrABC complex responsible for the process of nucleotide excision repair, was obtained. Growth, magnetosome formation and maintenance of magnetosome island (MAI) were further analyzed in the absence of UvrA. Interruption of uvrA led to decreased capacity to form magnetosome when cultured in the presence of oxygen. The deficiency in UvrA also resulted in an accelerated loss of the MAI under aerobic conditions indicating that the nucleotide excision repair system guards against the instability of the MAI. The incapacity of MTB to efficiently initiate recombination mediated by RecA rescued the instability of MAI observed in uvrA mutant. Elevated recombination activity resulting from the accumulation of unrepaired mutations may thus account for the instability of MAI in the absence of UvrA.


Identification of inhibitor-of-differentiation 2 (Id2) as a modulator of neuronal apoptosis.
Inhibitor-of-differentiation 2 (Id2) belongs to a family of transcriptional modulators that are characterized by a helix loop helix region but lack the basic amino acid domain. During development, Id2 antagonizes differentiation mediated by the retinoblastoma protein, probably by scavenging downstream E-box basic helix-loop-helix proteins. Here, using differential display RT-PCR, we identify Id2 as an induced gene during serum and potassium deprivation-induced apoptosis of cerebellar granule neurons. Consistent with a biological role for induced Id2 messenger RNA and protein expression in neuronal cell death, expression of Id2 antisense RNA, or targeted deletion of the Id2 gene in neurons from Id2 knock-out mice, protect from apoptosis. Further, gene transfer- mediated overexpression of Id2 induces neuronal cell death both in high potassium and low potassium conditions. Thus, the present study defines a role for Id2 in the modulation of neuronal apoptosis.


Dynamics of cortical progenitors and production of subcerebral neurons are altered in embryos of a maternal inflammation model for autism.
The broad impairments in cognitive and neurologic functioning found in Autism Spectrum Disorder (ASD) patients are thought to originate during early prenatal developmental stages. Indeed, postmortem and imaging studies in ASD patients detected white-matter abnormalities, as well as prefrontal and temporal cortex deficits, evident from early childhood. Here, we used Maternal Immune Activation (MIA), a mouse model for ASD, in which the offsprings exhibit Autistic-like behaviors as well as cortical abnormalities. However, the dynamics that influence the number and the identity of newly born cortical neurons following maternal inflammation remains unknown. Our study shows early changes in the duration of the S-phase of PAX6+ progenitors, leading to an increased proportion of neurogenic divisions and a reciprocal decrease in the proliferative divisions. In two different time points of maternal inflammation, MIA resulted in an overproduction of CTIP2+ cortical neurons, which remained overrepresented at the end of gestation and in postnatal mice. Interestingly, MIA-resistant IL6-KO mice did not exhibit these changes. Lastly, we propose that elevated levels of the transcription factor PAX6 following MIA supports the overproduction of CTIP2+ neurons. Taken together, our data reveals a possible link between maternal immune activation and the excess of cortical neurons found in the cortex of ASD patients.


Preparation and characterization of Pectin/Polypyrrole based multifunctional coatings on TiNbZr alloy for orthopaedic applications.
Being a natural and renewable polysaccharide, pectin (PC) is considered a polymer with promising potential for many applications. In the present investigation, novel multifunctional pectin/polypyrrole (PC/PPy) composite coatings loaded with gentamicin (GM) were electrochemically deposited on TiNbZr alloy to enhance its biocompatibility, antibacterial performance and corrosion resistance in physiological environment. Various surface and structural characterization techniques were deployed to examine the composite coatings. in vitro corrosion analysis confirmed that the composite coated TiNbZr specimen exhibited higher corrosion resistant performance in simulated body fluid (SBF). The drug release kinetics was estimated and the results corroborated the sustained release of GM from the controlled degradation of the composite matrix. The pectin composite coatings exhibited effective antibacterial performance; due to the sustained release of GM. In-vitro cell culture studies validated the improved biocompatibility of the composite coatings. Among the developed coatings, composite coatings loaded with 10 wt. % of GM exhibited the lowest corrosion rate, enhanced biocompatibility, and antibacterial performance.


Functionalized composite scaffolds improve the engraftment of transplanted dopaminergic progenitors in a mouse model of Parkinson's disease.
With the brain's limited capacity for repair there is a need for new and innovative therapies to promote regeneration. Stem/progenitor cell transplantation has received increasing attention, and whilst clinical trials demonstrating functional integration exist, inherent variability between patients has hindered development of this therapy. Variable outcomes have largely been attributed to poor survival and insufficient reinnervation of target tissues due in part to the suboptimal host environment. Here we examined whether improving the physical properties of the host milieu, by way of bioengineered scaffolds, may enhance engraftment. We developed a composite scaffold, incorporating electrospun poly(l-lactic acid) short nanofibers embedded within a thermo-responsive xyloglucan hydrogel, which could be easily injected into the injured brain. Furthermore, to improve the trophic properties of the host brain, glial derived neurotrophic factor (GDNF), a protein known to promote cell survival and axonal growth, was blended into and/or covalently attached onto the composite scaffolds to provide controlled delivery. In vitro we confirmed the ability of the scaffolds to support ventral midbrain (VM) dopamine progenitors, and provide sustained delivery of GDNF - capable of eliciting effects on cell survival and dopaminergic axon growth. In Parkinsonian mice, we show that these composite scaffolds, whilst having no deleterious impact on the host immune response, enhanced the survival of VM grafts and reinnervation of the striatum, an effect that was augmented through the scaffold delivery of GDNF. Taken together, these functionalized composite scaffolds provide a means to significantly improve the milieu of the injured brain, enabling enhanced survival and integration of grafted neurons.


Raman and resonance-Raman scattering by erythrocyte ghosts.
1. We present the laser-Raman spectra of human erythrocyte ghosts, isolated by standard conditions and compare these with the spectra of lecithin liposomes and fat-free serum albumin. 2. The hydrocarbon stretching modes of membrane lipids are temperature sensitive and may serve as a index of hydrocarbon chain motion. 3. The Amide I and Amide III bands of ghosts in H-2O and 2-H-2O, indicate a mixture of alpha-helical and unordered conformation, but do not allow a quantitative estimate of secondary structure. 4. Strong, scattering bands at 1530 and 1165 cm-1 are attributable to conjugated double bond systems, probably of membrane-associated carotenoids. Their high intensity is due to resonance enhancement.


Results-based financing to increase uptake of skilled delivery services in The Gambia: using the 'three delays' model to interpret midline evaluation findings.
Delays in accessing skilled delivery services are a major contributor to high maternal mortality in resource-limited settings. In 2015, the government of The Gambia initiated a results-based financing intervention that sought to increase uptake of skilled delivery. We performed a midline evaluation to determine the impact of the intervention and explore causes of delays. A mixed methods design was used to measure changes in uptake of skilled delivery and explore underlying reasons, with communities randomly assigned to four arms: (1) community-based intervention, (2) facility-based intervention, (3) community- and facility-based intervention, and (4) control. We obtained quantitative data from household surveys conducted at baseline (n = 1423) and midline (n = 1573). Qualitative data came from semi-structured interviews (baseline n = 20; midline n = 20) and focus group discussions (baseline n = 27; midline n = 39) with a range of stakeholders. Multivariable linear regression models were estimated using pooled data from baseline and midline. Qualitative data were recorded, transcribed, translated and thematically analyzed. No increase was found in uptake of skilled delivery services between baseline and midline. However, relative to the control group, significant increases in referral to health facilities for delivery were found in areas receiving the community-based intervention (beta = 0.078, p < 0.10) and areas receiving both the community-based and facility-based interventions (beta = 0.198, p < 0.05). There was also an increase in accompaniment to health facilities for delivery in areas receiving only community-based interventions (beta = 0.095, p < 0.05). Transportation to health facilities for delivery increased in areas with both interventions (beta = 0.102, p < 0.05). Qualitative data indicate that delays in the decision to seek institutional delivery usually occurred when women had limited knowledge of delivery indications. Delays in reaching a health facility typically occurred due to transportation-related challenges. Although health workers noted shortages in supplies and equipment, women reported being supported by staff and experiencing minimal delays in receiving skilled delivery care once at the facility. Focusing efforts on informing the decision to seek care and overcoming transportation barriers can reduce delays in care-seeking among pregnant women and facilitate efforts to increase uptake of skilled delivery services through results-based financing mechanisms.


An in silico evaluation of the ADMET profile of the StreptomeDB database.
Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability of such is vital for drug discovery protocols. This paper presents an assessment of the "drug-likeness" and pharmacokinetic profile of > 2,400 compounds of natural origin, currently available in the recently published StreptomeDB database. The evaluation of "drug-likeness" was performed on the basis of Lipinski's "Rule of Five", while 46 computed physicochemical properties or molecular descriptors were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. This survey demonstrated that, of the computed molecular descriptors, about 28% of the compounds within the StreptomeDB database were compliant, having properties which fell within the range of ADMET properties of 95% of currently known drugs, while about 44% of the compounds had ≤ 2 violations. Moreover, about 50% of the compounds within the corresponding "drug-like" subset showed compliance, while >83% of the "drug-like" compounds had ≤ 2 violations. In addition to the previously verified range of measured biological activities, the compounds in the StreptomeDB database show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery from natural sources. The generated data are available and could be highly useful for natural product lead generation programs.


Risk factors predicting upper urinary tract deterioration in patients with spinal cord injury: A retrospective study.
To determine the risk factors predicting upper urinary tract (UUT) deterioration in patients with spinal cord injury (SCI). Medical records of 303 SCI patients who referred to the urodynamic unit of a rehabilitation hospital between 1996 and 2003 were retrospectively reviewed. The data included general patient demographics, SCI characteristics, bladder management methods, serum creatinine level, presence of urinary tract infection, indwelling catheter time, radiological findings of upper and lower urinary tract, and video-urodynamic (VUD) findings. Univariate and multivariate analyses were used to determine the risk factors predicting UUT deterioration. ROC analysis was done to determine the cut-off values of detrusor pressure and cystometric bladder capacity volume predicting UUT deterioration. Complete data were available on 255 patients. Median patient age was 33 years (18-75). The leading causes of SCI were motor vehicle accidents (40%) and falls (29%). Upper urinary tract deterioration was determined in 63 patients (25%). Abnormal radiological LUT findings, the absence of antimuscarinic drug usage in the history, detrusor pressures greater than 75 cmH2 O and cystometric bladder capacity less than 200 ml were found to be independent risk factors in logistic regression analysis. ROC analysis revealed that values ≥75 cmH2 O for maximum detrusor pressure, <200 ml for bladder capacity, and >6 months for indwelling catheter time were cutoff values for UUT deterioration. Abnormal radiological LUT findings, the absence of antimuscarinic drug usage, detrusor pressures ≥75 cmH2 O, and cystometric bladder capacity <200 ml were independent risk factors predicting UUT deterioration SCI patients. Neurourol. Urodynam. 36:653-658, 2017. © 2016 Wiley Periodicals, Inc.


Strategy for the analysis of steryl esters from plant and animal tissues.
Methods are described for the analysis of intact steryl esters present in complex mixtures isolated from plant or animal tissues. A preliminary examination by analytical thin-layer chromatography (TLC) and capillary column gas chromatography-mass spectrometry (GC-MS) under electron impact (EI) ionisation reveals the complexity of the mixture and the nature of the steryl moieties. Preparative TLC is then utilised to separate the steryl esters into two broad groups, containing fatty acyl moieties of shorter (C2-C8) or longer chain length (C10-C22). The shorter-chain fatty acyl steryl esters are separated by adsorption high-performance liquid chromatography (HPLC) on a LiChrosorb Silica-60 column. The steryl esters with longer-chain fatty acyl moieties are analysed by reversed-phase HPLC on either an Ultrasphere ODS, 5-micron, or a S3 Spherisorb ODS, 3-micron, column. Steryl esters with unsaturated fatty acyl moieties are eluted with the shorter-chain fatty acyl steryl esters. The presence of the unsaturated fatty acyl esters can be monitored by analytical argentation TLC, which will also reveal the degree of unsaturation. The steryl esters are fractionated into the saturated, mono-, di-, tri- and polyene acyl types by preparative medium-pressure liquid chromatography on a column of 10% AgNO3-silica gel. Each of these steryl ester types can then be resubmitted to reversed-phase HPLC or analysed by GC-MS on a short fused-silica capillary column with a bonded phase of the OV-1 type. GC-MS on a magnetic-sector instrument under negative-ion chemical ionisation conditions with ammonia as the reagent gas produces fragment ions for both the steryl and fatty acyl moieties, thus permitting identification of the individual intact steryl esters. These various methods are illustrated by analyses of the steryl ester mixtures obtained from human plasma, barley seedlings, palm oil and rape seed oil.


Effect of an amniotic sheet on pregnancy outcomes.
Our aim was to evaluate whether the presence of an amniotic sheet affects obstetric and neonatal outcomes. All singleton pregnant women with and without a sonographic diagnosis of an amniotic sheet between the 16th and 24th weeks of pregnancy were retrospectively identified. Two women without an amniotic sheet were randomly selected from the similar stratified periods as a control group for each case. The demographic characteristics and obstetric and perinatal outcomes were compared between the groups. Multivariable logistic regression was also performed for potential confounding factors. In addition, the subsequent pregnancies of 12 women with an amniotic sheet were followed during the antenatal and postnatal periods. The prevalence of an amniotic sheet was 1.13%. The risk factors for an amniotic sheet were primiparity, previous normal vaginal delivery, previous dilation and curettage, and previous abortions. When the groups were compared in terms of maternal and neonatal outcomes, the rates of a nuchal cord at birth, breech birth, birth weight of less than 2500 g, preterm delivery (<37 weeks), and neonatal intensive care unit admission were higher in the amniotic sheet group than the control group. There were 2 intrauterine deaths in the amniotic sheet group. In addition, an amniotic sheet was not observed again in any of the subsequent pregnancies of the 12 cases from the amniotic sheet group, and these pregnancies eventuated uneventfully. An amniotic sheet is associated with an increase in poor obstetric outcomes. Therefore, close monitoring of pregnancies after diagnosis is required.


Health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer: A systematic review.
Elective neck dissection improves survival in early oral cancer. Sentinel lymph node biopsy may also do this with less morbidity. This systematic review compared health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer. PRISMA guidelines were followed. Thirteen studies met inclusion criteria. Results favoring sentinel lymph node biopsy were found in complications, scar length and appearance, length of hospital stay, time to drain removal, and objective shoulder measures at timepoints up to 12 months. Where differences in health-related quality of life were found, methodological issues make their clinical significance questionable. Sentinel lymph node biopsy was associated with fewer complications and statistically better outcomes in a number of physical measures. There is as yet no strong evidence to suggest it is associated with better health-related quality of life outcomes. While a number of health-related quality of life outcome measures show promise, their interpretation is hampered by methodological concerns. Further rigorous research is required to address this.


Rapid increase in cytosolic calcium ion concentration mediated by acetylcholine receptors in cultured retinal neurons and Müller cells.
This study was conducted to detect the presence of muscarinic or nicotinic receptors in cultured retinal neurons and Müller cells. Pure Müller cell cultures and cocultures of retinal neurons and Müller cells were used; the former, obtained from adult rabbit retinas, and the latter, retinal neurons from neonatal rats, were cocultured with Müller cells. Intracellular calcium ion concentration ([Ca2+]i) following the administration of acetylcholine, a cholinesterase inhibitor (trichlorfon), nicotine or muscarinic agonist with or without a receptor antagonist was monitored using the calcium ion indicator, fura-2. Acetylcholine and trichlorfon induced rapid increase in [Ca2+]i in half of either cell type. Trichlorfon induced positive response in coculture but not in the pure Müller cell cultures. This positive response was blocked only partially in the presence of atropine. Approximately 30-40% of neurons responded to nicotine at 5 microM, which was significantly blocked by alpha-bungarotoxin at 50 nM. No response to nicotine could be detected in Müller cells. Approximately 50% of neurons responded to muscarine at 50 microM, but 500 microM was required for the formation of calcium transients in 50% of Müller cells. The muscarine inducement of rapid increase in [Ca2+]i was blocked by atropine. The agonist of M1 (a muscarinic receptor subtype), McN-A-343, at 0.5 microM induced the most significant and rapid increase in [Ca2+]i both in neurons and Müller cells. McN-A-343 administration at 0.05 microM induced positive response in half the neurons, but only in approximately 10% of Müller cells. Such positive response was not observed following preincubation with the M1 antagonist, pirenzepine, at 50 microM. Cocultured retinal neurons enhance the release of acetylcholine following anticholinesterase administration, and approximately half the neurons were found to possess muscarinic and nicotinic receptors. However, Müller cells appeared to possess only the less sensitive muscarinic receptor. Muscarinic receptor subtypes on either type of cell contained at least M1.


Single-cell Raman microscopy with machine learning highlights distinct biochemical features of neutrophil extracellular traps and necrosis.
The defining biology that distinguishes neutrophil extracellular traps (NETs) from other forms of cell death is unresolved, and techniques which unambiguously identify NETs remain elusive. Raman scattering measurement provides a holistic overview of cell molecular composition based on characteristic bond vibrations in components such as lipids and proteins. We collected Raman spectra from NETs and freeze/thaw necrotic cells using a custom built high-throughput platform which is able to rapidly measure spectra from single cells. Principal component analysis of Raman spectra from NETs clearly distinguished them from necrotic cells despite their similar morphology, demonstrating their fundamental molecular differences. In contrast, classical techniques used for NET analysis, immunofluorescence microscopy, extracellular DNA, and ELISA, could not differentiate these cells. Additionally, machine learning analysis of Raman spectra indicated subtle differences in lipopolysaccharide (LPS)-induced as opposed to phorbol myristate acetate (PMA)-induced NETs, demonstrating the molecular composition of NETs varies depending on the stimulant used. This study demonstrates the benefits of Raman microscopy in discriminating NETs from other types of cell death and by their pathway of induction.


Signaling via the kinase p38α programs dendritic cells to drive TH17 differentiation and autoimmune inflammation.
Dendritic cells (DCs) bridge innate and adaptive immunity, but how DC-derived signals regulate T cell lineage choices remains unclear. We report here that the mitogen-activated protein kinase p38α programmed DCs to drive the differentiation of the T(H)17 subset of helper T cells. Deletion of p38α in DCs protected mice from T(H)17 cell-mediated autoimmune neuroinflammation, but deletion of p38α in macrophages or T cells did not. We also found that p38α orchestrated the expression of cytokines and costimulatory molecules in DCs and further 'imprinted' signaling via the receptor for interleukin 23 (IL-23R) in responding T cells to promote T(H)17 differentiation. Moreover, p38α was required for tissue-infiltrating DCs to sustain T(H)17 responses. This activity of p38α was conserved in mouse and human DCs and was dynamically regulated by pattern recognition and fungal infection. Our results identify p38α signaling as a central pathway for the integration of instructive signals in DCs for T(H)17 differentiation and inflammation.


Author Correction: The rapid electrochemical activation of MoTe2 for the hydrogen evolution reaction.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Pubertal Synchrony and Depressive Symptoms: Differences by Race and Sex.
Individual differences in the timing and tempo of pubertal development have been shown to be related to depressive symptoms during adolescence, particularly among girls. Another measure of variability in pubertal development is pubertal synchrony, the degree to which the development of pubertal indicators (e.g., breast growth and ancillary hair growth) are synchronized within the individual. Pubertal synchrony also has been hypothesized to be related to depressive symptoms, but, to date, only one study has tested this hypothesis. However, it remains unclear whether pubertal synchrony confers risk for depressive symptoms more proximally in time or differentially among boys or non-White youth. The current study examined the relation between pubertal synchrony and depressive symptoms concurrently and six months later as a function of race and sex in a community sample of 215 youth (53% female, 44.7% African American; mean age = 12.90 years (SD = 0.86)). Girls with asynchronous development at Time 1 reported significantly higher depressive symptoms at Time 2 than girls with synchronous development and boys with asynchronous development. In addition, boys with asynchronous development at Time 1 had lower depressive symptoms at Time 2 than boys with synchronous development. Race did not moderate pubertal synchrony-depression relations. These results suggest that pubertal asynchrony is a risk factor for girls, but a protective factor for boys, and lend support for pubertal synchrony as a potential contributor to the gender gap in depression that emerges during adolescence.


Incomplete Records as a Leading Cause of Missed Opportunity for Human Papillomavirus Vaccine Initiation in a Safety Net Health System.
The goal of this study was to categorize reasons behind missed opportunities for human papillomavirus (HPV) vaccine initiation in an under-resourced population and to identify associated patient and clinic characteristics. Manual chart review was performed for patients aged 11 to 18 years who visited a primary care clinic in a health system in Texas, USA between 06/01/18 and 08/31/18 and were due for an initial HPV vaccine dose but did not receive it. Reasons for HPV vaccine noninitiation were categorized as follows: incomplete immunization record, no documentation of discussion (no documentation that the HPV vaccine was offered or ordered), refusal, staff/provider error, and medical. Multinomial logistic regression was used to examine factors associated with each category. Of 4467 adolescents seen in the study period, 575 (12.9%) were due for the first dose of HPV vaccine but did not receive it. The most common reason for noninitiation was incomplete immunization record (37%), followed by no documentation of discussion (24%), refusal (20%), staff/provider error (15%), and medical (4%). The highest odds of incomplete immunization were among older adolescents. The highest odds of no documentation of discussion were during sick visits. The highest odds of staff/provider error were among patients with commercial insurance. The lowest odds of refusal were in patients with county/indigent insurance. The most common reason for missed opportunity visits for HPV vaccine initiation was lack of adequate immunization records. Our study highlights the importance of immunization record access and bidirectional reporting as important targets for future interventions.


Molecular aspects of the inactivation of tryptophanyl transfer ribonucleic acid synthetase by N-ethylmaleimide.
The tryptic maps of tryptophanyl-tRNA synthetase from beef pancreas show that the 8 cysteinyl residues of the enzyme subunit are located, 2 by 2, on four different peptides. The kinetics of the incorporation of radioactivity from N-[ethyl-14C]ethylmaleimide into these peptides are compared in this paper with the kinetics of the changes of the catalytic properties of the enzyme occurring during alkylation. This comparison allows the identification of (a) the peptide carrying the cysteinyl residues located on the surface of the molecule, (b) the peptide carrying the deeply buried residues unmasked by the dissociation of the subunits, and (c) the peptide carrying the --SH group located in the vicinity of the binding site of tryptophan. The fourth peptide is shown to have a great sensitivity to pH with respect to the reactivity of its cysteinyl residues toward N-ethylmaleimide. The same unusual pH dependence is found for the rate of quenching of the intrinsic fluorescence of the protein during the alkylation, suggesting a strong sensitivity of the conformation of tryptophanyl-tRNA synthetase to pH in the range of 7 to 9.


PrEP Whores and HIV Prevention: The Queer Communication of HIV Pre-Exposure Prophylaxis (PrEP).
HIV pre-exposure prophylaxis (PrEP) has been introduced as another biomedical tool in HIV prevention. Whereas other such tools-including post-exposure prophylaxis (PEP) and interruption of perinatal transmission-have been embraced by those impacted by HIV, PrEP has been met with more conflict, especially within the gay community and HIV organizations. The "PrEP whore" has come to designate the social value and personal practices of those taking PrEP. This study examines the "PrEP whore" discourse by using queer theory and quare theory. Within these theoretical vantage points, the study explicates four discursive areas: slut shaming, dirty/clean binaries, mourning the loss of condoms, and reclaiming the inner whore. The study illuminates possible discursive strategies that lie outside of the domains of public health and within the individual and community.


Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough.
This self-matched control study aimed to compare the efficiency of two different regimens of active treatment: aspirin in low (100 mg daily) versus intermediate (500 mg daily) doses in abolishing angiotensin-converting enzyme inhibitor (ACEI)-induced cough. A dry bothersome cough is the most common adverse class effect of all angiotensin-converting enzyme inhibitors. Prostaglandins (PG) have been pinpointed as playing a leading role in the genesis of ACEI-associated cough. The role of different doses of the most commonly used PG inhibitor-aspirin-in ACEI cough modification was not yet elucidated. Of 350 consecutive ACEI-treated patients, we identified 34 (9.7%) nonsmoking ACEI-related coughers. Patients with lung disease, nonsteroidal anti-inflammatory drug (NSAID) treatment, and those who did not agree to participate in the study were excluded. In the remaining 14 ACEI coughers (eight men, six women; mean age, 63 +/- 11 years), the treatment was discontinued; the dry cough completely disappeared, but returned in all patients within 1 week after ACEI reintroduction. At the end of the rechallenge period, patients started a low dose of aspirin for 1 week, switching thereafter to the intermediate dose of aspirin for an additional week. On each visit the cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin were ineffective in suppressing ACEI-induced cough, whereas intermediate doses completely abolished cough in five patients and reduced coughing in all but one patient; CS and CF decreased, respectively, from 2.5 +/- 1.0 to 0.9 +/- 1.1, P < .002 and from 6.6 +/- 2.4 to 2.4 +/- 1.1, P < .0002. Overall, intermediate doses of aspirin beneficially modified cough scores in 13 (93%) patients, enabling nine (64%) to continue ACEI treatment. Aspirin did not influence blood pressure control either in hypertensives or in postinfarction patients. We conclude that intermediate but not low doses of aspirin probably can suppress ACEI-induced cough. These findings propose a new alternative therapeutic approach for patients with ACEI-related cough, especially those in whom ACEI treatment seems to be essential.


Photosensitized cleavage and cross-linking of pBR322 DNA with khellin and visnagin.
The naturally occurring furanochromones khellin and visnagin have received considerable attention, largely because of their vasodilatory properties and of their ability (particularly that of khellin) to induce skin pigmentation upon ultraviolet light treatment of patients suffering from vitiligo. There are conflicting statements in the literature on whether or not they are capable of cross-linking DNA photochemically. Supercoiled and linear pBR322 DNA was used to probe this reaction. The results showed that both khellin and, to a greater extent, visnagin photosensitized DNA cross-linking. In addition, both photosensitizers induced extensive DNA cleavage.


Mechanics of the cellular actin cortex: From signalling to shape change.
The actin cortex is a thin layer of actin, myosin and actin-binding proteins that underlies the membrane of most animal cells. It is highly dynamic and can undergo remodelling on timescales of tens of seconds, thanks to protein turnover and myosin-mediated contractions. The cortex enables cells to resist external mechanical stresses, controls cell shape and allows cells to exert forces on their neighbours. Thus, its mechanical properties are the key to its physiological function. Here, we give an overview of how cortex composition, structure and dynamics control cortex mechanics and cell shape. We use mitosis as an example to illustrate how global and local regulation of cortex mechanics gives rise to a complex series of cell shape changes.


Application of UHPLC for the determination of free amino acids in different cheese varieties.
A rapid ultra-high performance liquid chromatography (UHPLC) protocol for the determination of amino acids as their respective 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatives was successfully applied for assessing free amino acid levels in commercial cheese samples representing typical product groups (ripening protocols) in cheesemaking. Based on the Waters AccQ.Tag™ method as a high performance liquid chromatography (HPLC) amino acid solution designed for hydrolyzate analyses, method adaptation onto UHPLC was performed, and detection of AQC derivatives was changed from former fluorescence (λ(Ex) 250 nm/λ(Em) 395 nm) to UV (254 nm). Compared to the original HPLC method, UHPLC proved to be superior by facilitating excellent separations of 18 amino acids within 12 min only, thus demonstrating significantly shortened runtimes (>35 min for HPLC) while retaining the original separation chemistry and amino acid elution pattern. Free amino acid levels of the analyzed cheese samples showed a high extent of variability depending on the cheese type, with highest total amounts found for original Italian extra-hard cheeses (up to 9,000 mg/100 g) and lowest for surface mold- or bacterial smear-ripened soft cheeses (200-600 mg/100 g). Despite the intrinsic variability in both total and specific concentrations, the established UHPLC method enabled reliable and interference-free amino acid profiling throughout all cheese types, thus demonstrating a valuable tool to generate high quality data for the characterization of cheese ripening.


Neurological update: consult the neurosurgical oracle for a standard operating procedure.
Standard operating procedures (SOPs) contain general instructions and principles to standardize care, to improve effective and safe healthcare. Developing new, or updating current, SOPs is, however, challenging in fields where high-level evidence is limited. Still, SOPs alone have been shown to result in less complications. In this narrative review, we describe the process of creating a consensus-based SOP that is pragmatic for clinical practice since it can be created regardless of the current level of evidence. Through live audience engagement platforms, a group of experts will be able to both anonymously respond to a created questionnaire, and (subsequently) discuss the results within the same meeting. This modified Digital Delphi method as described here can be used as a tool toward consensus-based healthcare.


Pyrrolidinedithiocarbamate induces apoptosis in human acute myelogenous leukemic cells affecting NF-kappaB activity.
Pyrrolidindithiocarbamate (PDTC), is a metal chelator widely used to study the activation of redox sensitive transcription factors. Recently it has been demonstrated that it manifests pro-oxidant properties. The nuclear factor-Kappa B (NF-kappaB) transcription factor can both promote cell survival and induce apoptosis depending on cell type and context in response to genotoxic stress. In our previous study we reported that in acute myelogenous leukemia CD34+ cells PDTC stimulates apoptosis, whereas in CD34+ cells of healthy volunteers PDTC was ineffective. This cytotoxicity was dependent on the generation of superoxide anion and oxidized glutathione. In this article we have shown that the pro-oxidant effect of PDTC in AML cells induces NF-kappaB activity. These findings imply a role for NF-kappaB in the survival of normal cells with respect to leukemic cells, suggesting that NF-kappaB activity and function differs according to tumor cell phenotype.


A direct test of Listing's law--I. Human ocular torsion measured in static tertiary positions.
The validity of Listing's law was reinvestigated by means of a direct test. Horizontal, vertical and torsional eye movements were measured simultaneously with a recently developed scleral induction coil. Either eye of 4 subjects was measured monocularly. Eye position were measured in Fick coordinates and ocular torsion values were compared to the theoretical ones predicted by Listing's law. During consecutive measurements in the primary position torsion values were close to zero although considerable fluctuations of torsion were seen. Torsion values in the secondary positions were also close to zero. In the tertiary positions torsion in the direction as predicted by Listing's law and increasing with eccentricity was recorded. In the temporal quadrants mean torsion was quantitatively in agreement with Listing's law; torsion values in the nasal quadrants however showed systematically larger values and this discrepancy increased with eccentricity to more than 50%. Statistical support for this finding however, was seen only in 4 out of 8 eyes. Symmetry could be obtained by shifting the chosen horizontal primary position (gaze parallel to the midplane) in the temporal direction; as a consequence all measured torsion values would exceed the ones specified by Listing's law. Torsion values varied idiosyncratically among subjects and among the left and right eyes of any one subject. It is concluded that Listing's law specifies ocular torsion only approximately: physiological eye movements show considerable stochastical as well as systematical deviations from this law.


Virtual space created by a digital platform in the post epidemic context: The case of Greek museums.
This study aims to develop a conceptual model for the application of digital technology in museums, using a case study of a cultural site in Greece. Museums, as sites of cultural transmission and regeneration and the embodiment of local culture, influence not only the cultural vitality of communities and regions but also the power of this culture to spread globally. Against the backdrop of Greece's announcement of the gradual restoration of public places, it is crucial to rebuild local cultural sites and strengthen cultural heritage protection. This article proposes a conceptual model suitable for digital museums, which integrates the spatiotemporal relationship between ruins and social groups in digital virtual space, and obtains two potential research concepts: "the extension of time and space" and "thin-wall communication". These results can be used to optimize the reconstruction of cultural place.


A review on lung disease recognition by acoustic signal analysis with deep learning networks.
Recently, assistive explanations for difficulties in the health check area have been made viable thanks in considerable portion to technologies like deep learning and machine learning. Using auditory analysis and medical imaging, they also increase the predictive accuracy for prompt and early disease detection. Medical professionals are thankful for such technological support since it helps them manage further patients because of the shortage of skilled human resources. In addition to serious illnesses like lung cancer and respiratory diseases, the plurality of breathing difficulties is gradually rising and endangering society. Because early prediction and immediate treatment are crucial for respiratory disorders, chest X-rays and respiratory sound audio are proving to be quite helpful together. Compared to related review studies on lung disease classification/detection using deep learning algorithms, only two review studies based on signal analysis for lung disease diagnosis have been conducted in 2011 and 2018. This work provides a review of lung disease recognition with acoustic signal analysis with deep learning networks. We anticipate that physicians and researchers working with sound-signal-based machine learning will find this material beneficial.


Obesity alters the topographical distribution of ventilation and the regional response to bronchoconstriction.
Obesity is associated with reduced operating lung volumes that may contribute to increased airway closure during tidal breathing and abnormalities in ventilation distribution. We investigated the effect of obesity on the topographical distribution of ventilation before and after methacholine-induced bronchoconstriction using single-photon emission computed tomography (SPECT)-computed tomography (CT) in healthy subjects. Subjects with obesity (n = 9) and subjects without obesity (n = 10) underwent baseline and postbronchoprovocation SPECT-CT imaging, in which Technegas was inhaled upright and followed by supine scanning. Lung regions that were nonventilated (Ventnon), low ventilated (Ventlow), or well ventilated (Ventwell) were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. To determine regional ventilation, lungs were divided into upper, middle, and lower thirds of axial length, derived from CT. At baseline, Ventnon and Ventlow for the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Ventnon (17.5 ± 10.6% vs. 34.7 ± 7.8%, P < 0.001) and Ventlow (25.7 ± 6.3% vs. 33.6 ± 5.1%, P < 0.05) were decreased in subjects with obesity, with a consequent increase in Ventwell (56.8 ± 9.2% vs. 31.7 ± 10.1%, P < 0.001). The greater diversion of ventilation to the upper zone was correlated with body mass index (rs = 0.74, P < 0.001), respiratory system resistance (rs = 0.72, P < 0.001), and respiratory system reactance (rs = -0.64, P = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Ventnon increased similarly in both groups; however, in subjects without obesity, Ventnon only increased in the lower zone, whereas in subjects with obesity, Ventnon increased more evenly across all lung zones. In conclusion, obesity is associated with altered ventilation distribution during baseline and following bronchoprovocation, independent of reduced lung volumes.NEW & NOTEWORTHY Using ventilation SPECT-computed tomography imaging in healthy subjects, we demonstrate that ventilation in obesity is diverted to the upper lung zone and that this is strongly correlated with body mass index but is independent of operating lung volumes and of airway closure. Furthermore, methacholine-induced bronchoconstriction only occurred in the lower lung zone in individuals who were not obese, whereas in subjects who were obese, it occurred more evenly across all lung zones. These findings show that obesity-associated factors alter the topographical distribution of ventilation.


The Utility of the Two-Step Gender Measure Within Trans and Cis Populations.
It has been acknowledged that more research into the health and well-being of trans people is needed in order to identify important health issues. While recent studies have suggested using a two-question gender status measure to assess assigned sex at birth and gender identity, it is not well understood how participants understand and subsequently answer the questions. The study recruited a convenience sample of 50 people (25 trans and 25 cis) from the general population of Cleveland and Akron, OH. The study used cognitive interviewing methods with scripted, semi-structured and spontaneous probes when appropriate. Participants were asked to read questions out-loud, answer the questions, and explain why they answered the way they did. Interviews were audio recorded and transcribed prior to analysis. The gender status questions were found to be easy to use and understood by both trans and cis participants. The two-question gender status measure was able to encompass a diversity of identities within a trans sample and be consistently answered by the study's cis participants. The measures were able to differentiate between trans and cis groups. The two-step gender measure can be a useful tool in examining gender diversity within general population studies.


B-cells of the synovial membrane. II. Differentiation during development of the synovial cavity in the mouse.
Study of pre- and postnatal development of the metatarsophalangeal joint of the mouse shows that the synovial cavity (SC) forms before any differentiation of the synovial mesenchyme. The primitive cleft results from degradation of a thin vascular mesenchymal layer in direct contact with the chondrogenic layers. Differentiation of the synovial membrane coincides with clarification of the SC (3rd to 6th day of postnatal life). When dilatation of the SC occurs (6th to 8th day), the two intimal cells types (A- and B-cells) are well identified. The B-cells already show typical features at day 6; their content of typical dense secretory vesicles is comparable to that of the adult B-cells at day 13. The specific secretory function of B-cells could be correlated with the particular structure of the intimal interstitial tissue and could account for the origin of some protein(s) of the synovial fluid.


Effect of insulin supplementation on in vitro maturation of pre-antral follicles from adult and pre-pubertal mice.
This study was aimed to determine the impact of insulin concentrations on in vitro pre-antral follicle growth, survival, antrum formation rate, and retrieval of mature oocytes in mice. Mice pre-antral follicle growth were recorded on days 2, 4, 6, 8, 10, and 12 in α-modified essential media (α-MEM) supplemented with insulin concentrations of 6, 8, and 10 μg/ml along with 10% FBS, 100 mIU/ml follicle stimulating hormone, 10 mIU/ml luteinizing hormone, 100 μg/ml penicillin, and 50 μg/ml streptomycin. After 12 d of growth in vitro, follicles were allowed to mature for 16-18 h in α-MEM supplemented with 1.5 IU/ml human chorionic gonadotrophin (hCG) and 5 ng/ml epidermal growth factor (EGF). The initial diameter (54.86 ± 2.5 μm) of mice oocyte progressively increased in all the three insulin concentration groups and attained a maximum size on day 12 (71.90 ± 2.8 μm). Supplementation with higher concentrations of insulin (both 8 and 10 μg/ml) significantly enhanced antrum formation without effecting the oocyte diameter and percent retrieval of mature oocyte in all the three concentration groups. Both in vitro cultured as well as in vivo collected follicles and oocytes showed similar localization and expression of oocyte maturation markers SAS1B and GDF9. Insulin concentration of 8 μg/ml was found to be optimal for in vitro follicle culture of adult mice (42-49 d). Optimized follicle culture conditions were also assessed successfully with pre-pubertal mice (12-14 d); however, adult mice showed higher follicle survival, antrum formation, and more mature oocytes production in comparison to pre-pubertal mice.


A Systematic Review and Meta-Analysis Examining the Impact of Sleep Disturbance on Postoperative Delirium.
Basic science and clinical studies suggest that sleep disturbance may be a modifiable risk factor for postoperative delirium. We aimed to assess the association between preoperative sleep disturbance and postoperative delirium. We searched PubMed, Embase, CINAHL, Web of Science, and Cochrane from inception until May 31, 2017. We performed a systematic search of the literature for all studies that reported on sleep disruption and postoperative delirium excluding cross-sectional studies, case reports, and studies not reported in English language. Two authors independently performed study selection and data extraction. We calculated pooled effects estimates with a random-effects model constructed in Stata and evaluated the risk of bias by formal testing (Stata Corp V.14, College Station, TX), DATA SYNTHESIS:: We included 12 studies, from 1,238 citations that met our inclusion criteria. The pooled odds ratio for the association between sleep disturbance and postoperative delirium was 5.24 (95% CI, 3.61-7.60; p < 0.001 and I = 0.0%; p = 0.76). The pooled risk ratio for the association between sleep disturbance and postoperative delirium in prospective studies (n = 6) was 2.90 (95% CI, 2.28-3.69; p < 0.001 and I = 0.0%; p = 0.89). The odds ratio associated with obstructive sleep apnea and unspecified types of sleep disorder were 4.75 (95% CI, 2.65-8.54; p < 0.001 and I = 0.0%; p = 0.85) and 5.60 (95% CI, 3.46-9.07; p < 0.001 and I = 0.0%; p = 0.41), respectively. We performed Begg's and Egger's tests for publication bias and confirmed a null result for publication bias (p = 0.371 and 0.103, respectively). Preexisting sleep disturbances are likely associated with postoperative delirium. Whether system-level initiatives targeting patients with preoperative sleep disturbance may help reduce the prevalence, morbidity, and healthcare costs associated with postoperative delirium remains to be determined.


Isolation and partial characterization of secreted mouse pituitary prolactin.
Prolactin secreted by mouse anterior pituitaries was purified by gel filtration on Sephadex G-100. Electrophoretic homogeneity of the purified hormone was demonstrated in several gel systems, and electrophoresis in the presence of sodium dodecyl sulfate indicated an apparent molecular weight of 21 000 +/- 2000. Mouse and ovine prolactin displayed parallel dose vs. response curves in radio-receptor binding studies, indicating that these two hormones compete for identical receptor sites on rabbit mammary membranes. Comparative peptide mapping studies carried out on tryptic digests of mouse and ovine prolactin suggested only partial homology between the two hormones. Internally labeled monomeric mouse prolactin was observed to undergo aggregation following storage at --20 degrees C for 2 months.


Chronic kidney disease of unknown aetiology in Sri Lanka and the exposure to environmental chemicals: a review of literature.
Chronic kidney disease of unknown aetiology (CKDu) has emerged as a serious health issue in Sri Lanka. The disease has been recorded in the North Central Province of the country. While studies have elicited many hypotheses concerning the pathogenicity of CKDu, none adequately explains the cause of CKDu and the measures needed to minimise its occurrence. Nephrotoxic heavy metal (oid)s such as cadmium, arsenic, lead, and chromium are present in biological samples of people from endemic areas. This review appraises evidence on the effects of long-term exposure to low concentration of nephrotoxic heavy metals, which could be the principal cause of CKDu. Although a considerable variation exists in metal concentrations in patients' blood and urine, higher levels of heavy metals were consistently observed in affected areas. This review finds that the populations in the endemic areas are exposed to heavy metal (oid)s at low concentrations, which are considered as safe levels; nevertheless, it influences the incidence of CKDu. Recent global studies on chronic kidney disease (CKD) revealed a low concentration of heavy metals in diseased patients. Research findings indicated that CKDu patients in Sri Lanka demonstrated similar blood levels of Cd, Pb, and higher concentrations of Cr than that have been reported globally. Further studies on the influence of combinations of nephrotoxic heavy metals at low concentrations on reduced glomerular filtration rate and other renal biomarkers could explain CKDu pathogenicity.


Evaluation of growth, primary productivity, nutritional composition, redox state, and antimicrobial activity of red seaweeds Gracilaria debilis and Gracilaria foliifera under pCO2-induced seawater acidification.
The genus Gracilaria is an economically important group of seaweeds as several species are utilized for various products such as agar, used in medicines, human diets, and poultry feed. Hence, it is imperative to understand their response to predicted ocean acidification conditions. In the present work, we have evaluated the response of Gracilaria foliifera and Gracilaria debilis to carbon dioxide (pCO2) induced seawater acidification (pH 7.7) for two weeks in a controlled laboratory conditions. As a response variable, we have measured growth, productivity, redox state, primary and secondary metabolites, and mineral compositions. We found a general increase in the daily growth rate, primary productivity, and tissue chemical composition (such as pigments, soluble and insoluble sugars, amino acids, and fatty acids), but a decrease in the mineral contents under the acidified condition. Under acidification, there was a decrease in malondialdehyde. However, there were no significant changes in the total antioxidant capacity and a majority of enzymatic and non-enzymatic antioxidants, except for an increase in tocopherols, ascorbate and glutathione-s-transferase in G. foliifera. These results indicate that elevated pCO2 will benefit the growth of the studied species. No sign of oxidative stress markers indicating the acclimatory response of these seaweeds towards lowered pH conditions. Besides, we also found increased antimicrobial activities of acidified samples against several of the tested food pathogens. Based on these observations, we suggest that Gracilaria spp. will be benefitted from the predicted future acidified ocean.


Recent developments in the use of arthroscopy in cattle.
Diagnostic arthroscopy can be applied to the bovine stifle to directly visualize the menisci, cranial and caudal cruciate ligaments, the articular surfaces, and the synovium. Basic arthroscopic technique for the bovine stifle hock is described using line drawings and endophotography. Examples of joint lesions as seen through the arthroscope and at postmortem dissection are presented.


The antidepressant venlafaxine may act as a neurodevelopmental toxicant in cuttlefish (Sepia officinalis).
The Serotonin/Norepinephrine Reuptake Inhibitor (SNRI) antidepressant venlafaxine (VEN, Effexor(®)) has become one of the most common antidepressants detected in North American and European streams. Mammalian research has established that VEN exposure is associated with a range of structural, neurochemical, and functional alterations of the brain in adults and newborns. However, the neurodevelopmental effects of VEN on non-target organisms have never been investigated. The aim of our research was to decrease this gap in knowledge by characterizing the effects of VEN exposure on a cephalopod mollusk, the common cuttlefish Sepia officinalis. This species inhabits VEN-contaminated waters and possesses an unusually sophisticated brain. These characteristics render it a unique invertebrate species for studying the neurodevelopmental effects of VEN. Cuttlefish were exposed to environmentally-relevant concentrations of VEN (Measured concentrations ≈5 and 100ngL(-)(1)) or to filtered natural seawater (control) in a closed-loop system with regular water changes during the first 20days after hatching. We evaluated brain maturation as well as neurochemical changes and behavioral performances during this critical period of development. Our results show that both VEN-exposed groups exhibited a decrease in norepinephrine levels, along with a reduction in the relative number of glutamate NMDA-like receptors binding sites in the group exposed to 5ngL(-1) of VEN after 20days of exposure. Brain regional changes in cellular proliferation were observed in VEN-exposed groups in the vertical lobe (i.e. a key structure involved in cognitive processes) and in the optic lobes (i.e. main visual processing centers) in the absence of significant change in their volume. Along with these neurodevelopmental changes, 20days of exposure to 100ngL(-1) of VEN was associated with a decrease in camouflage ability. Overall, our study suggests that VEN is a neurodevelopmental toxicant in non-target aquatic organisms at environmentally-relevant concentrations.


Relationship between race and clinical characteristics, extent of disease, and response to chemotherapy in patients with low-risk gestational trophoblastic neoplasia.
To evaluate the potential effects of race on clinical characteristics, extent of disease, and response to chemotherapy in women with postmolar low-risk gestational trophoblastic neoplasia (GTN). This non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained. Of 316 women, 274 (86.7%) were white, 19 (6%) African American, and 23 (7.3%) Asian. African Americans were significantly younger than white and Asian women (p=0.008). Disease presentation, and extent of disease, including antecedent molar histology, median time to persistence, median hCG level at persistence, rate of D&C at persistence, presence of metastatic disease, and FIGO stage and risk score were similar among races. Need for second line chemotherapy (p=0.023), and median number of regimens (p=0.035) were greater in Asian women than in other races. Low-risk GTN was more aggressive in Asian women, who were significantly more likely to need second line chemotherapy and a higher number of chemotherapy regimens to achieve complete remission than women of African American and Asian descent. Further studies involving racial differences related to clinical, biological and environmental characteristics are needed.


Crystal structure of the p38α MAP kinase in complex with a docking peptide from TAB1.
The mitogen-activated protein kinase (MAPK) p38α is a key regulator in many cellular processes, whose activity is tightly regulated by upstream kinases, phosphatases and other regulators. Transforming growth factor-β activated kinase 1 (TAK1) is an upstream kinase in p38α signaling, and its full activation requires a specific activator, the TAK1-binding protein (TAB1). TAB1 was also shown to be an inducer of p38α's autophosphorylation and/or a substrate driving the feedback control of p38α signaling. Here we determined the complex structure of the unphosphorylated p38α and a docking peptide of TAB1, which shows that the TAB1 peptide binds to the classical MAPK docking groove and induces long-range conformational changes on p38α. Our structural and biochemical analyses suggest that TAB1 is a reasonable substrate of p38α, yet the interaction between the docking peptide and p38α may not be sufficient to trigger trans-autophosphorylation of p38α.


Prescription analgesic and antidepressant utilization and cost among elderly Medicaid beneficiaries before and after nursing home admission.
The objectives of this study were to describe changes in prescription analgesic and antidepressant medications and to track the costs associated with these medication changes when elderly Medicaid beneficiaries move from the community to a nursing home setting. Retrospective analysis of Medicaid long-term care and drugs claims data for fiscal year 2000 from three different states. Long-term care facilities in three different states. We studied 1321 elderly Medicaid beneficiaries newly admitted to a nursing home during the study period. Pain medications were grouped into four different categories and all antidepressants were grouped into one category. For each medication category, we obtained the number of unique patients for whom it was prescribed, the number of days it was prescribed, and the amount paid by Medicaid. We then calculated the percentage of subjects prescribed and the amount paid per day for each medication class before and after nursing home admission. Except for skeletal muscle relaxants, 21% to 39% of beneficiaries already had claims linked to each medication class while still living in the community. After nursing home admission, the percentage of beneficiaries exposed to each medication class increased by 2% to 33%. Cost per day of therapy increased by 10% to 83%. There was significant variation among the states in utilization and cost per day of therapy. We draw three major conclusions: (1) community-dwelling elderly Medicaid beneficiaries in this study use more prescription analgesics and antidepressants than community-dwelling elders in prior studies; (2) there is a significant increase in medication utilization and cost on nursing home admission; and (3) significant variability in medication use and cost exists among the three states examined. Further investigation to elucidate the reasons for these differences could assist legislators in formulating sound public policy to contain Medicaid expenditures without sacrificing patient care.


Use of Organs from SARS-CoV-2 Infected Donors: Is It Safe? A Contemporary Review.
As the prevalence of individuals with recovered coronavirus disease 2019 (COVID-19) increases, determining if and when organs from these donors can be safely used is an important priority. We examined current knowledge of outcomes of transplant using donors with recovered COVID-19. A literature search of PubMed and Google scholar databases was conducted to identify articles with terms "SARS-CoV2," "COVID-19," "donor recovered," and "transplantation" published through 08/10/2021. We identified 25 reports detailing 94 recipients of both abdominal and thoracic transplants from donors with both prior and active COVID-19 infection. Rates of transmission to the recipient and of transplanted organ dysfunction were low among reports of donors with prior COVID-19 infection. End organ dysfunction and transmission were more common with active infection, although few reports are available. Standardized reporting is needed to better assess the impact of donor symptomatology, cycle thresholds, and individual recipient risk factors on postoperative outcomes. Available reports suggest that transplantation from COVID-19 donors may be feasible and safe, at least in short term follow-up. Nevertheless, there is a need for standardized testing and management protocols which should be tailored for available resources. While increased availability of COVID-19 vaccinations will mitigate risks of donor-derived COVID-19 and simplify management, continued vigilance is warranted during the ongoing public health emergency.


2-({[4-(1,3-Benzothia-zol-2-yl)phen-yl]amino}methyl)-phenol.
In the title compound, C(20)H(16)N(2)OS, the aniline substituent essentially coplanar with the benzothia-zole moiety (with an r.m.s. deviation of all fitted non-H atoms of 0.0612 Å). The phenol group is almost perpendic-ular to the benzothia-zolylaniline group, with an inter-planar angle of 88.36 (2)°. In the crystal, mol-ecules aggregate as centrosymmetric dimers by pairs of O-H⋯N hydrogen bonds. C-H⋯O contacts and N-H⋯π(arene) inter-actions also occur.


The potential to avoid heart transplantation in children: outpatient bridge to recovery with an intracorporeal continuous-flow left ventricular assist device in a 14-year-old.
Pediatric mechanical circulatory support has evolved considerably in the past decade. Improvements in device design and availability have led to increased short-, medium-, and long-term support options for pediatric patients with heart failure. Most pediatric mechanical circulatory support is utilized as a bridge to transplant and as a bridge to recovery in patients with temporary etiologies of heart failure (i.e., myocarditis). Described herein is our recovery program, and we report our experience as an independent pediatric ventricular assist device program with an intracorporeal continuous-flow device employed as an out-of-hospital bridge to recovery for a child with end-stage chronic heart failure.


HNRNPC as a candidate biomarker for chemoresistance in gastric cancer.
Chemoresistance is a major cause of treatment failure and high mortality in advanced gastric cancer (AGC). Currently, the mechanism of chemoresistance remains unclear, and there is no biomarker to accurately predict the efficacy of chemotherapy. In the present study, we established human gastric cancer (GC) cell lines resistant to 5-fluorouracil (5FU), paclitaxel (TA), or cisplatin (DDP) by gradient drug treatment and generated a novel monoclonal antibody 5B2 targeting heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) overexpressed in chemoresistant GC cells. Overexpressing HNRNPC in GC cells promoted chemoresistance, and knockdown of HNRNPC by small interfering RNA (siRNA) reversed chemoresistance. By utilizing available datasets, we demonstrated that high level of HNRNPC transcript indicated poor overall survival (OS) and free of progression (FP). HNRNPC expression was negatively correlated with OS of GC patients treated with 5FU-based drugs and with time to progression (TTP) of GC patients treated with CF regimen. These data suggest the potential usefulness of HNRNPC as a prognostic and therapeutic marker of GC.


Inclusion body myositis: its relative frequency in elderly people.
Inclusion body myositis (IBM) is a distinct, steroid resistant, form of inflammatory myopathy. Its recognition is the more important because of the preponderant occurrence in the elderly, in whom steroid treatment is hazardous. Since the relative frequency of IBM among inflammatory myopathies in the elderly is undetermined, we retrospectively studied its frequency among all our patients over 50 years, diagnosed between 1980 and 1991 with inflammatory myopathy. Nine of 15 patients with inflammatory myopathy appeared to suffer from IBM. In a further 2 patients this diagnosis was strongly suspected. We conclude that IBM is the most frequent inflammatory myopathy in the elderly. This observation warrants restraint with steroids in the management of inflammatory myopathy in the elderly.


Feedback-controlled dextrose infusion during surgical management of insulinomas.
Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.


Magnetic resonance imaging of postrepair-myelomeningocele--findings in 31 children and adolescents.
Magnetic resonance imaging has clearly demonstrated its efficacy in the diagnosis of pathological processes in the C.N.S. We examined 31 children who had undergone plastic closure of myelomeningocele a few days post partum. We could show that a high percentage of the patients (89%) presented the pathological anatomy of a tethered spinal cord; clinical symptoms of the tethered spinal cord syndrome, i.e. progressive neurological symptoms, however, are rarely observed. Possible revision of neurosurgical treatment of MMC is discussed.


Self-Supported, Sulfate-Functionalized Nickel Hydroxide Nanoplates with Enhanced Wettability and Conductivity for Use in High-Performance Supercapacitors.
Nickel hydroxide is promising for use in supercapacitor applications because of its low cost and tunable electrochemical properties, but its performance is usually restricted by insufficient conductivity and surface reactivity. In this work, sulfate-functionalized Ni(OH)2 (SNO) nanoplates were grown in situ on nickel foam (NF) by a green and facile one-step hydrothermal treatment of NF without the need for an external Ni source or surfactant addition. The resulting material showed a 9.3 times higher areal capacity and 1.8 times higher rate capability than the sulfate-free control and retained 81.3 % capacity after 5000 cycles. If used as the positive electrode in a hybrid supercapacitor, the SNO/NF//activated carbon system achieved >95 % Coulombic efficiency, a maximum energy density of 3.59 Wh m-2 , and a maximum power density of 44.63 Wm-2 , which surpass those achievable by most known Ni-based supercapacitors. Detailed material characterization and DFT calculations revealed that the introduction of sulfate expanded the layer spacing of Ni(OH)2 and improved the electrical conductivity and wettability to favor more efficient electrolyte diffusion, charge transfer, and reactant adsorption. The high loading of reactive components and inherited porous structure also contributed to the superior capacitive performance of the SNO/NF electrodes. Therefore, SNO/NF holds great potential for commercialized supercapacitor applications.


Salicylate antagonizes the antiinflammatory action of aspirin in the rat.
On the ground of conflicting evidence concerning the interaction of salicylate and aspirin, we investigated the results of such interaction on carrageenin edema of the rat hind paw. Aspirin and sodium salicylate were administered by stomach tube either singly or in combination, at a dose of 50 mg/kg each. The antiinflammatory effect was significantly greater when aspirin was administered prior to salicylate than when aspirin followed salicylate. It is therefore suggested that salicylate may antagonize the action of aspirin in vivo, and that the temporal order in which the two drugs interact with cyclooxygenase may be an important determinant of the outcome.


Assessing performance of closed-loop insulin delivery systems by continuous glucose monitoring: drawbacks and way forward.
We investigated whether continuous glucose monitoring (CGM) levels can accurately assess glycemic control while directing closed-loop insulin delivery. Data were analyzed retrospectively from 33 subjects with type 1 diabetes who underwent closed-loop and conventional pump therapy on two separate nights. Glycemic control was evaluated by reference plasma glucose and contrasted against three methods based on Navigator (Abbott Diabetes Care, Alameda, CA) CGM levels. Glucose mean and variability were estimated by unmodified CGM levels with acceptable clinical accuracy. Time when glucose was in target range was overestimated by CGM during closed-loop nights (CGM vs. plasma glucose median [interquartile range], 86% [65-97%] vs. 75% [59-91%]; P=0.04) but not during conventional pump therapy (57% [32-72%] vs. 51% [29-68%]; P=0.82) providing comparable treatment effect (mean [SD], 28% [29%] vs. 23% [21%]; P=0.11). Using the CGM measurement error of 15% derived from plasma glucose-CGM pairs (n=4,254), stochastic interpretation of CGM gave unbiased estimate of time in target during both closed-loop (79% [62-86%] vs. 75% [59-91%]; P=0.24) and conventional pump therapy (54% [33-66%] vs. 51% [29-68%]; P=0.44). Treatment effect (23% [24%] vs. 23% [21%]; P=0.96) and time below target were accurately estimated by stochastic CGM. Recalibrating CGM using reference plasma glucose values taken at the start and end of overnight closed-loop was not superior to stochastic CGM. CGM is acceptable to estimate glucose mean and variability, but without adjustment it may overestimate benefit of closed-loop. Stochastic CGM provided unbiased estimate of time when glucose is in target and below target and may be acceptable for assessment of closed-loop in the outpatient setting.


Passive biophysical membrane properties of nucleus reticularis gigantocellularis neurons in brain slices from the rat.
This study employed intracellular recording coupled with the current clamp technique to characterize the passive biophysical membrane properties of neurons in the nucleus reticularis gigantocellularis (NRGC) of brain slices from adult, male Sprague-Dawley rats. We found that NRGC neurons possessed highly depolarized transmembrane potentials (-22.9 +/- 0.6 mV, n = 189). The 29 NRGC neurons that received further evaluation showed that they could be separated into two clusters, with significantly different membrane input resistances (3.51 +/- 0.89 vs 77.50 +/- 8.82 M omega) and membrane time constants (0.56 +/- 0.05 vs 1.27 +/- 0.12 ms). These membrane properties, which resembled qualitatively those we observed previously in cats in vivo, will form the basis for further evaluation of the ionic mechanisms that may underlie the actions of pharmacologic agents on the NRGC neurons.


Surface projections and internal structure of Chlamydia psittaci.
The outermost surface of the small infectious forms of Chlamydia psittaci contain geometrically arranged spikes distributed over approximately 50% of the bacterial surface. The spikes are located opposite the concave side of an electron-dense crescent-shaped chlamydial core.


Early Use of Norepinephrine Improves Survival in Septic Shock: Earlier than Early.
The timing of initiation of Norepinephrine (NEP) in septic shock is controversial. We evaluated the impact of early NEP simultaneously with fluids in those patients. We randomized 101 patients admitted to the emergency department with septic shock to early NEP simultaneously with IV fluids (early group) or after failed fluids trial (late group). The primary outcome was the in-hospital survival while the secondary outcomes were the time to target mean arterial pressure (MAP) of 65 mmHg, lactate clearance and resuscitation volumes. There was no significant difference between the two groups regarding the baseline characteristics. NEP infusion started after 25 (20-30) and 120 (120-180) min in the early and late groups (p = 0.000). MAP of 65 mmHg was achieved faster in the early group (2 [1-3.5] h vs. 3 [2-4.75] h, p = 0.003). Serum lactate was decreased by 37.8 (24-49%) and 22.2 (3.3-38%) in both groups respectively (p = 0.005). Patients with early NEP were resuscitated by significantly lower volume of fluids (25 [18.8-28.7] mL/kg vs. 32.5 [24.4-34.6] mL/kg) in the early and late groups (p = 0.000). The early group had survival rate of 71.9% compared to 45.5% in the late group (p = 0.007). NEP started after 30 (20-120 min) in survivors vs. 120 (30-165 min) in non-survivors (p = 0.013). We concluded that early Norepinephrine in septic shock might cause earlier restoration of blood pressure, better lactate clearance and improve in-hospital survival.


Outcomes of colostomy takedown following Hartmann's procedure: successful restoration of continuity comes with a high risk of morbidity.
Restoration of bowel continuity following a Hartmann's procedure is a major surgical undertaking associated with significant morbidity. The aim of this study was to review the authors' experience with Hartmann's reversal. This was a retrospective review of consecutive patients from institutional databases who were selected to undergo open or laparoscopic Hartmann's reversal at two tertiary academic referral centres and a public safety net hospital (2010-2019). The main outcome measure was the rate of successful stoma reversal. Secondary outcomes included 30-day postoperative outcomes and procedural details. One hundred and fifty patients underwent attempted reversal during the study period, which was successful in all but three patients (98%). Patients were 59% Hispanic and 73% male, with a mean age of 48.7 ± 14.1 years, mean American Society of Anesthesiologists classification of 2.2 ± 0.6 and mean body mass index (BMI) of 28.6 ± 5.3 kg/m2 , with 39% of patients having a BMI > 30 kg/m2 . The mean time interval between the index procedure and reversal was 14.4 months, 53% of the index cases were performed at outside institutions and the most common index diagnoses were diverticulitis (54%), abdominal trauma (16%) and colorectal malignancy (15%). In 22% of cases a laparoscopic approach was used, with 42% of these requiring conversion to open. Proximal diverting stomas were created in 32 patients (21%), of which 94% were reversed. The overall morbidity rate was 54%, comprising ileus (32%), wound infection (15%) and anastomotic leak (6%), with a major morbidity rate (Clavien-Dindo ≥ 3) of 23%. Hartmann's reversal remains a highly morbid procedure. Our results suggest that operative candidates can be successfully reversed, but there is significant morbidity associated with restoration of intestinal continuity, particularly in obese patients. A laparoscopic approach may decrease morbidity in selected patients but such cases have a high conversion rate.


Outcomes Associated with Introduction of the 5th Generation High-Sensitivity Cardiac Troponin in Patients Presenting with Cardiovascular Disorders.
The new high-sensitivity cardiac troponin T (hs-cTnT) is now widely used in the United States. We aimed to examine outcomes associated with the introduction of the new 5th generation hs-cTnT assay among patients presenting to the emergency department (ED) with cardiovascular (CV) disorders. The study comprised 5377 patients presenting to the ED with CV disorders between January and September 2018. Outcomes included rates of direct ED discharge, cardiac testing/procedures, and mortality. CV indications for troponin testing were categorized as rule-out acute coronary syndrome (RO-ACS) and other-CV (O-CV). Mean age was 62 ± 17 years, and 47% were female. Demographics and medical history did not differ significantly between the troponin groups. The use of hs-cTnT was associated with increased rates of direct discharge from the ED in the RO-ACS (48% vs. 37%; p < 0.01), but not in the O-CV (25% vs. 25%) cohort. Cardiac tests/procedures were more often performed after hs-cTnT vs. cTnT testing in both cohorts (45% vs. 41% for RO-ACS, and 33% vs. 28% for O-CV; p < 0.05 for both). Multivariate analysis demonstrated that hs-cTnT was not associated with a significant increase in postdischarge mortality in both cohorts (RO-ACS: hazard ratio = 1.47 [p = 0.13], O-CV: hazard ratio = 0.97 [p = 0.87]). Among patients with RO-ACS, hs-cTnT implementation resulted in increased rates of direct home discharge from the ED, without a significant increase in postdischarge mortality. Among patients presenting with O-CV indication, hs-cTnT implementation resulted in increased rates of cardiac testing procedures without an effect of ED discharge rates or long-term mortality.


2-(2-Methylfuran-3-carboxamido)-3-phenylpropanoic acid, a potential CYP26A1 inhibitor to enhance all-trans retinoic acid-induced leukemia cell differentiation based on virtual screening and biological evaluation.
To develop new CYP26A1 inhibitors, a three-cycle virtual screening was carried out based on the constructed homology model of human CYP26A1 using Dock, Fred, Gold and AutoDock. Twenty-two compounds exhibited high scores and reasonable binding modes in molecular docking were purchased from Specs Company. Eighteen compounds were tested their abilities to enhance ATRA-induced differentiation in human acute promyelocytic leukemia NB4 cells. Eight of them enhanced the ability of ATRA to induce differentiation at concentrations of 0.5 and 1 μM. Among these compounds, 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid (S8) is of most effective in blocking ATRA breaking down in NB4 cells based on the LC-MS/MS assay.


Spatiotemporal dynamics analysis of aquaculture zones and its impact on green tide disaster in Haizhou Bay, China.
With the rapid marine economic development, the problem of the marine ecological environment has become progressively prominent. Mariculture monitoring plays an essential role in sustaining ecological stability, rational planning, and green economic development of sea areas. Using the Landsat image, the raft-mariculture area information of Haizhou Bay and its adjacent southern waters were extracted by the object-oriented classification method based on remote sensing techniques. Landscape pattern index and principal component analysis were used to analyze the spatiotemporal expansion and structural changes of mariculture areas, and to quantify the effects of natural, socio-economic factors on the spatiotemporal variations of mariculture areas. This study discusses the correlation between the mariculture area and the outbreak scale of Enteromorpha Enteromorpha green tide. Results show that the object-oriented classification method has the highest accuracy, with total classification accuracy and Kappa coefficient of more than 90% and 0.79, respectively. The total area, patch density, and landscape shape index of mariculture areas in Haizhou Bay increase yearly, which demonstrates that the heterogeneity and fragmentation increase with the expansion of the mariculture area. The landscape pattern changes in the mariculture area are predominantly impacted by annual mean sea surface temperature (SST), annual average wind speed, social development level, and population density, etc. The larger the area of raft-aquaculture, the wider the outbreak scale of the Enteromorpha prolifera disaster. Study results can provide scientific references for the further development of mariculture in Haizhou Bay and marine environmental protection.


Conversion of viable but nonculturable enteric bacteria to culturable by co-culture with eukaryotic cells.
Viable but nonculturable (VBNC) Vibrio cholerae non-O1/non-O139, V. parahaemolyticus, enterohemorrhagic Escherichia coli, enterotoxigenic E. coli, enteropathogenic E. coli, Shigella flexneri, and Salmonella enterica were converted to the culturable state by co-culture with selected eukaryotic cells, e.g., HT-29, Caco-2, T84, HeLa, Intestine 407, and CHO cells.


miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy.
Activation of nuclear factor -kappa B (NF-κB) is associated with inflammation in the progression of diabetic nephropathy (DN). MiR-451 is closely linked to renal damage in DN. Large multifunctional protease 7 (LMP7), an immunoproteasome subunit, can activate NF-κB. However, it remained unclear whether miR-451 affected NF-κB-induced inflammation by regulating LMP7 in DN. In this study, deep sequencing, in situ hybridization, quantitative real-time PCR, dual-luciferase reporter gene assays, western blot and chromatin immunoprecipitation were respectively used. For the results, we found that miR-451 was markedly downregulated in the kidneys of db/db mice, PBMCs of DN patients and mesangial cells (MCs) cultured in high glucose conditions. Furthermore, miR-451 directly targeted LMP7 expression to inhibit NF-κB activity, and down-regulated transcription of proinflammatory molecules in MCs. More importantly, in the kidneys of db/db DN mice, increasing miR-451 level inhibited LMP7/NF-κB activity, and attenuated the urinary microalbumin excretion, blood glucose, and glomerular injury. In conclusion, these results provide new insights into the regulation of miR-451 via the LMP7/NF-κB central inflammatory pathway during progression of DN.


Utilization and impact of ambulance diversion at the community level.
To evaluate the utilization and impact of ambulance diversion in the metropolitan area of Syracuse, New York. This was a retrospective review of the ambulance diversion system operated by the hospitals of Syracuse, New York. This system allows each emergency department to divert incoming ambulances during periods of extreme overcrowding. Data collected included numbers of hours on ambulance diversion by hospital, numbers of hours when all four hospitals were on diversion simultaneously, and numbers of ambulances received while the hospitals were on and off diversion. For three of the five years evaluated, ambulance diversion hours were most numerous during the period between January and March. For the most recent year studied (2000), ambulance diversion hours did not decline after the first quarter. During periods of diversion, hospital emergency departments received 30%-50% fewer ambulances than they did while open. This study demonstrated that, in Syracuse, New York, ambulance diversion was once a seasonal phenomenon, but is increasingly occurring throughout the year because of staff and resource limitations. It also demonstrated that ambulance diversion can be employed to reduce numbers of incoming transports.


Evaluation of fentanyl immunoassay test strips for rapid in-situ detection of fentanyl and fentanyl analogs in seized samples and alternative matrices.
Ion mobility spectrometry is used for the rapid detection of drugs at points of security but are unable to differentiate some drugs leading to the instrument alarming for a drug not present in the sample. This can be particularly problematic for samples that alarm for fentanyl. In this study, fentanyl immunoassay strips were evaluated for use as a secondary test for fentanyl, including for the testing of alternative matrices, such as powders, e-liquids, and infused papers and textiles. The limit of detection of fentanyl immunoassay strips was examined along with their selectivity to 18 fentanyl analogsand 72 other drugs and cutting agents. The effectiveness of the test strips at the detection of fentanyl in the presence of other drugs was examined by testing a series of concentrations of fentanyl in solution in combination with other drugs. The testing of alternative matrices was explored with laboratory prepared samples through sampling with cotton buds and extraction in water. The fentanyl immunoassay strips detected fentanyl at concentrations of 45 ng/mL and reacted with 16 of 18 tested fentanyl analogs with carfentanil and norfentanyl being the only analogs to not react. There was no reactivity with other drugs or cutting agents. The effectiveness of the fentanyl test strips was not reduced when fentanyl was mixed with other drugs. Fentanyl was successfully detected with high sensitivity in all alternative matrices. The fentanyl immunoassay strips were found to be an effective secondary test for fentanyl and at least 16 fentanyl analogs in seized drug samples, including when mixed with other drugs. The effectiveness of the sampling methods for alternative matrices should be further evaluated using fentanyl and fentanyl analog casework samples. The use of this method by law enforcement and other agencies should be examined to assess its effectiveness and ease of use in operational settings.