Multi-residue method for the determination of 16 recently used pesticides from various chemical groups in aqueous samples by using DI-SPME coupled with GC-MS.
A simple and solvent-free multi-residue method has been optimized to determine 16 currently used pesticides from different chemical groups in aqueous samples. The extraction of analytes was carried out with direct immersion solid-phase microextraction (DI-SPME) and for the identification and quantitative determination gas chromatography coupled with mass spectrometry (GC-MS) was applied. Two commonly used adsorbent coatings have been applied and compared: 100 μm of polydimethylsiloxane (PDMS) and 85 μm of polyacrylate (PA). The method development parameters of DI-SPME, analyte desorption and GC-MS analysis have been outlined along with the final experimental conditions. When the optimum extraction conditions were applied (extraction time 60 min, 10% (w/v) NaCl solution, 45°C) the limits of detection (LODs) were in the range of 0.015-0.13 μgL(-1) and the relative standard deviations (RSDs) were between 1.9 and 9.6%. The developed analytical method was successfully applied to the analysis of natural water samples from the following sources: river, sea, canal and rain.


[Participation of the orienting-exploratory reaction in the formation of a secondary signal association system in lecture instruction].
The close correlation between the skin galvanic reaction (SGR) and the process of formation of scientific knowledge (abstract-logical temporal connections) has been shown by using SGR for the determination of the secondary signal system activity. Rather a high level of each student's SGR is kept during the whole lecture. The more active the student's SGR is mobilized the more efficient the scientific knowledge is learnt.


Q fever vaccines for animals.
The results of different workgroups and those obtained in own investigations with Q fever vaccines for cattle and sheep are reviewed and discussed. In field trials Coxiella (C.) burnetii vaccines of inactivated whole cells (WC) in phase (ph) I as well as WC ph II vaccines prevented infections of cows exposed to naturally infected environments, provided they were vaccinated as noninfected calves. To monitor calves for this purpose the sensitive ELISA has superseded the complement fixation test (CF). WC ph I vaccines failed to prevent shedding by uninfected cattle and sheep which were vaccinated and subsequently challenged by parenteral inoculation with viable organisms, but reduced shedding, and prevented pathological lesions and clinical symptoms. The results obtained in field trials with a commercially available vaccine consisting of killed WC ph II of C. burnetii and inactivated WC of Chlamydia psittaci indicated that vaccination had significantly improved fertility in vaccinated herds. However, the mechanism of protection is unclear because the function of the chlamydial component in this vaccine is not yet defined. Cattle given this vaccine can be distinguished from naturally infected cattle because the former produce predominantly non-complement-binding IgG2, detectable by ELISA. This vaccine frequently causes undesirable local reactions. Antigens of C. burnetii (strain "Frankfurt", ph II) prepared by propagation in cell cultures and successive purification by guanidinium hydrochloride- and chloroform/methanol-extraction (CMR), as well as a major protein extracted from these CMR preparations represent potential vaccine candidates without such side effects.


Impaired bone health as a co-morbidity of epilepsy.
Increasing number of studies shows significant reductions in bone mineral density in patients with epilepsy treated with enzyme-inducing anti-seizure medications (EIASM), valproic acid, and newer anti-seizure medications (ASM). ASM seems to be a specific risk factor for the development of osteoporosis affecting 11%-31% of patients with epilepsy and leads to 2 to 6 times increased risk of fractures compared to the background population. Treatment with ASM clearly contributes to epilepsy-associated bone disease. Yet, the exact pathophysiological mechanism has not been established; however, several hypotheses were suggested, especially in relation to EIASM. As the long-lasting medical treatment, often in polytherapy, has shown negative effects on bone health, it indicates the need for guidelines for the prevention and management of bone disease to be included in the follow-up of patients with epilepsy. An algorithm for following bone status during the treatment has been suggested based on Danish national guidelines.


Partial purification and some biochemical properties of neonatal rat cutaneous glutathione S-transferases.
1. Previous studies have demonstrated the presence of glutathione S-transferases in the skin of rodents and humans. This study represents the first attempt to purify cytosolic glutathione S-transferases from skin of 3-day-old rats. 2. A partial purification of the enzyme was achieved by a two-step procedure: affinity chromatography followed by HPLC. Two peaks, one major (P-1) and one minor (P-2), were resolved by HPLC containing about 82% and 10% of the recovered activity, respectively. 3. The major form exhibited an overall purification of about 2270-fold with a specific activity of about 73 mumoles/min/mg protein towards 1-chloro-2,4-dinitrobenzene. 4. The kinetic data for P-1 yielded mean Km values of 2.39 mM for 1-chloro-2,4-dinitrobenzene and 0.72 mM for reduced glutathione, while the respective average Vmax values were found to be 212 and 101 mumoles/min/mg protein. 5. Significantly inhibition of enzyme activity was noted in the presence of 0.2 mM HgCl2, 0.63 microM 1.2-naphthoquinone, 1.0 microM triphenyltin chloride, and 12.5 microM 17 beta-estradiol-3-sulfate.


Mesenchymal Stem Cell-Derived Extracellular Vesicles: An Emerging Diagnostic and Therapeutic Biomolecules for Neurodegenerative Disabilities.
Mesenchymal stem cells (MSCs) are a type of versatile adult stem cells present in various organs. These cells give rise to extracellular vesicles (EVs) containing a diverse array of biologically active elements, making them a promising approach for therapeutics and diagnostics. This article examines the potential therapeutic applications of MSC-derived EVs in addressing neurodegenerative disorders such as Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Furthermore, the present state-of-the-art for MSC-EV-based therapy in AD, HD, PD, ALS, and MS is discussed. Significant progress has been made in understanding the etiology and potential treatments for a range of neurodegenerative diseases (NDs) over the last few decades. The contents of EVs are carried across cells for intercellular contact, which often results in the control of the recipient cell's homeostasis. Since EVs represent the therapeutically beneficial cargo of parent cells and are devoid of many ethical problems connected with cell-based treatments, they offer a viable cell-free therapy alternative for tissue regeneration and repair. Developing innovative EV-dependent medicines has proven difficult due to the lack of standardized procedures in EV extraction processes as well as their pharmacological characteristics and mechanisms of action. However, recent biotechnology and engineering research has greatly enhanced the content and applicability of MSC-EVs.


Leishmania (L.) infantum BH401 strain induces classic renal lesions in dogs: Histological and confocal microscopy study.
Extracellular matrix (ECM) alterations in visceral leishmaniasis are related mainly to collagen deposition (fibropoiesis). In canine visceral leishmaniasis (CVL), an intense fibrosis associated to chronic inflammation in organs such as kidneys is described. However, renal fibropoiesis has not been described in natural or experimental infections with L. (L.) infantum. We aimed to characterize renal nephropathies by histology and confocal microscopy comparing renal lesions in dogs naturally and experimentally infected with L. (L.) infantum. Sixty-two mixed-breed symptomatic dogs naturally infected with L. (L.) infantum, sixteen beagles experimentally infected with two strains of L. infantum (eleven dogs with the BH400 strain and five dogs with the BH401 strain), and five uninfected beagles (controls) were used. Samples were stained with hematoxylin & eosin for routine histology. Congo red was used to visualize amyloid protein deposits, periodic acid-Schiff to identify glomerular basal membrane anomalies, Masson's trichrome for collagen deposits, and Jones' methenamine silver to reveal membranous glomerulonephropathy. Immunohistochemistry was used to identify Leishmania amastigotes, and confocal microscopy was used for macrophage characterization (L1/calprotectin and CD163 antigen receptors). The most common lesions were chronic glomerular and interstitial nephritis, which was found in all naturally infected dogs and dogs experimentally infected with L. infantum strain BH401 but not with the BH400 strain. Glomeruloesclerosis was the main lesion presented in all BH401 group. Morphometric analysis revealed positive correlation of renal glomeruli tufts with cellular expression of L1/calprotectin and CD163 antigens. Leishmania infantum strain BH401 shows pathogenicity that may be sufficient to induce classic chronic visceral renal leishmaniasis.


Inferring pathological states in cortical neuron microcircuits.
The brain activity is to a large extent determined by states of neural cortex microcircuits. Unfortunately, accuracy of results from neural circuits׳ mathematical models is often biased by the presence of uncertainties in underlying experimental data. Moreover, due to problems with uncertainties identification in a multidimensional parameters space, it is almost impossible to classify states of the neural cortex, which correspond to a particular set of the parameters. Here, we develop a complete methodology for determining uncertainties and the novel protocol for classifying all states in any neuroinformatic model. Further, we test this protocol on the mathematical, nonlinear model of such a microcircuit developed by Giugliano et al. (2008) and applied in the experimental data analysis of Huntington׳s disease. Up to now, the link between parameter domains in the mathematical model of Huntington׳s disease and the pathological states in cortical microcircuits has remained unclear. In this paper we precisely identify all the uncertainties, the most crucial input parameters and domains that drive the system into an unhealthy state. The scheme proposed here is general and can be easily applied to other mathematical models of biological phenomena.


Kainate-induced calcium overload of cortical neurons in vitro: Dependence on expression of AMPAR GluA2-subunit and down-regulation by subnanomolar ouabain.
Whereas kainate (KA)-induced neurodegeneration has been intensively investigated, the contribution of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in neuronal Ca2+ overload ([Ca2+]i) is still controversial. Using Ca2+ imaging and patch-clamp techniques, we found different types of Ca2+ entry in cultured rat cortical neurons. The presence of Ca2+ in the extracellular solution was required to generate the [Ca2+]i responses to 30 μM N-methyl-d-aspartate (NMDA) or KA. The dynamics of NMDA-induced [Ca2+]i responses were fast, while KA-induced responses developed slower reaching high [Ca2+]i. Ifenprodil, a specific inhibitor of the GluN2B subunit of NMDARs, reduced NMDA-induced [Ca2+]i responses suggesting expression of GluN1/GluN2B receptors. Using IEM-1460, a selective blocker of Ca(2+)-permeable GluA2-subunit lacking AMPARs, we found three neuronal responses to KA: (i) IEM-1460 resistant neurons which are similar to pyramidal neurons expressing Ca(2+)-impermeable GluA2-rich AMPARs; (ii) Neurons exhibiting nearly complete block of both KA-induced currents and [Ca2+]i signals by IEM-1460 may represent interneurons expressing GluA2-lacking AMPARs and (iii) neurons with moderate sensitivity to IEM-1460. Ouabain at 1 nM prevented the neuronal Ca2+ overload induced by KA. The data suggest, that cultured rat cortical neurons maintain functional phenotypes of the adult brain cortex, and demonstrate the key contribution of the Na/K-ATPase in neuroprotection against KA excitotoxicity.


Descriptive Aspects of Injection Drug Users in Iran's National Harm Reduction Program by Methadone Maintenance Treatment.
The Ministry of Health, Treatment and Medical Education of Iran has recently announced an estimated figure of 200,000 injecting drug users (IDUs). The aim of this study was to pilot a national program using demographics, types of drug abuse and prevalence of blood-borne infections among IDUs. In order to elicit data on demographics, types of drug abuse and prevalence of blood-borne infections among IDUs, a questionnaire was designed in the Bureau of Mental-Social Health and Addiction in collaboration with Iran's Drug Control Headquarters of the Police Department. Therapeutical alliance of addiction in Shafagh Center was based on Methadone Maintenance Therapy (MMT). Among 402 reported IDUs most of them were male, single and in age range of 20 to 39 years old with 72.7% history of imprisonment. Most of them had elementary and high school education and a history of addiction treatment. The majority were current users of opioid, heroin and crack. The prevalence of blood-borne infections was 65.9% and 18.8% for HCV and HIV/AIDS infections, respectively. Prevention programs about harm reduction, treatment and counseling should include young IDUs as a core focus of their intervention structure.


Quality of bitewing radiographs in children in relation to the type of film holder used.
To assess the frequency of use with young uncooperative children of the bitewing radiograph film holders: KWIK-BITE, Snap-a-ray, and a Sticky tape, and to compare the quality of bitewing radiographs achieved with these types of film holders. This retrospective study assessed 298 pairs of bitewing radiographs of children aged 3-14 years. The radiographs were evaluated according to age, type of behavioural management approach used, extent and degree of overlapping surfaces, visibility of the alveolar bone, and the presence of folds, cone-cut and elongated teeth. Snap-a-ray was used more frequently in younger children (p < 0.001), less cooperative children (p < 0.001), and in those who were treated under sedation (p < 0.001). The KWIK-BITE holder was used more frequently in older children (p < 0.001), cooperative children (p = 0.001), and in those under general anaesthesia (p < 0.001). About 76.5 % of the radiographs contained technical errors. The degree of overlapping surfaces in radiographs was not correlated with the type of film holder used, but rather with the degree of children's cooperation. The Snap-a-ray film holder was used more frequently in young uncooperative children; nevertheless, its use was not associated with an increased frequency or degree of overlapping surfaces.


Iatrogenic false aneurysms following punch hair grafting.
By serial angiograms, we found the pulsating nodules occasionally seen after punch hair grafting are pseudoaneurysms.


Pharmacokinetic and pharmacodynamic properties of inhaled beclometasone dipropionate delivered via hydrofluoroalkane-containing devices.
Inhaled corticosteroids have a key role in the treatment of asthma and chronic obstructive pulmonary disease. In recent times, beclometasone dipropionate has been reformulated in pressurised metered dose inhalers (pMDIs), using hydrofluoroalkanes (HFAs) as a propellant. Extensive toxicological testing has shown that HFA-propellants are well tolerated. Among the reformulated beclometasone dipropionate-containing pMDIs, only the characteristics of the two Qvar formulations have been thoroughly explored. Compared to the reference beclometasone dipropionate formulation, the mass median aerodynamic diameter of the Qvar formulations are substantially smaller (1.1 vs 4.0 microm), whereas that of Modulite averages 2.6 microm. Scintigraphic and pharmacokinetic studies indicate a higher lung deposition for both the Qvar and the Beclazone formulations, compared with reference beclometasone dipropionate formulation. Since the 2- to 3-fold increase in pulmonary deposition results in a 2.6- to 3-fold difference in relative efficacy for Qvar, half the dose of the reference beclometasone dipropionate formulation has been currently recommended in adult patients with asthma, a recommendation that is supported by a large number of clinical trials. Conversely, the design of the studies conducted to compare the efficacy of Qvar with fluticasone propionate and budesonide does not allow establishing their equivalence on a milligram per milligram basis. Good studies on the bioequivalence between the reference beclometasone dipropionate formulation and the Modulite or Beclazone formulations are not available.


Quality Control Approach to Anticoagulants and Transfusion.
Quality can be defined by processes of care and by the characteristics of the care and its outcomes. In terms of blood loss and transfusion, otolaryngologists should be aware of available guidelines, standards for use of blood products, devices and hemostatic agents, outcomes metrics relevant to patients, and tools for implementing quality improvements. This article reviews the definition of health care quality, and discusses the data regarding anticoagulant medications (particularly new oral anticoagulants) and guidelines for blood product transfusion. A brief outline of quality tools is provided to help otolaryngologists create quality plans for themselves and their institutions/systems.


The potential application of electrochemical biosensors in the COVID-19 pandemic: A perspective on the rapid diagnostics of SARS-CoV-2.
Electrochemical biosensors combine the selectivity of electrochemical signal transducers with the specificity of biomolecular recognition strategies. Although they have been broadly studied in different areas of diagnostics, they are not yet fully commercialized. During the COVID-19 pandemic, electrochemical platforms have shown the potential to address significant limitations of conventional diagnostic platforms, including accuracy, affordability, and portability. The advantages of electrochemical platforms make them a strong candidate for rapid point-of-care detection of SARS-CoV-2 infection by targeting not only viral RNA but antigens and antibodies. Herein, we reviewed advancements in electrochemical biosensing platforms towards the detection of SARS-CoV-2 through studying similar viruses.


Pregnancy, birth and neonatal outcomes associated with reduced fetal movements: A systematic review and meta-analysis of non-randomised studies.
Maternal perception of reduced fetal movements (RFM) is identified as an important alarm signal for possible risk of impending adverse perinatal outcomes. Perinatal outcomes associated with RFM are increasingly being investigated in non-randomised studies with several associated outcomes, including stillbirth, preterm birth, fetal growth restriction and neonatal death being reported. Findings from studies, however, are conflicting. To synthesise the findings of published studies regarding pregnancy, birth and neonatal outcomes in women who presented with RFM. PubMed, EMBASE, CINAHL complete, Maternity and Infant Care, PsycINFO, and Science Citation Index databases were searched up to 8th July 2021 and updated again on 8th September 2022. Non-randomised studies involving pregnant women ≥24 weeks' gestation, who presented with a primary complaint of RFM compared to women who did not present with RFM were included. Data were meta-analysed using a random-effects model and presented as Odds Ratios (OR) or Standard Mean Differences (SMD) with 95% Confidence Intervals (CI). Thirty-nine studies were included. Women with RFM had increased odds of stillbirth (OR 3.44, 95% CI 2.02-5.88) and small for gestational age (OR 1.37, 95% CI 1.16-1.61) when compared with women who did not have RFM. Associations were also found for induction of labor, instrumental birth and caesarean section but not for preterm birth (OR 0.92, 95% CI 0.71-1.19) or neonatal death (OR 0.99; 95% CI 0.52-1.90). This review revealed that RFM is associated with increased odds of stillbirth, small for gestational age, induction of labor, instrumental birth and caesarean section but not preterm birth or neonatal death.


Metabolic neuropathies and myopathies.
Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney.


Wearable Biosensors in Congenital Heart Disease: Needs to Advance the Field.
Traditional measures of clinical status and physiology have generally been based in health care settings, episodic, short in duration, and performed at rest. Wearable biosensors provide an opportunity to obtain continuous non-invasive physiologic data from patients with congenital heart disease (CHD) in the real-world setting, over longer durations, and across varying levels of activity. However, there are significant technical limitations to the use of wearable biosensors in CHD. Here, we review current applications of wearable biosensors in CHD; how clinical and research uses of wearable biosensors must consider various CHD physiologies; the technical challenges in developing wearable biosensors for CHD; and special considerations for digital biomarkers in CHD.


Preparation of bioactive functional poly(lactic acid)/curcumin composite film for food packaging application.
Poly (lactic acid)-based functional films incorporated with curcumin have been prepared using a solution casting method. The PLA/curcumin composite film was flexible and highly transparent with bright yellow color. Curcumin was uniformly dispersed in the PLA matrix and showed excellent compatibility with PLA, as evidenced by the FE-SEM, DSC and FTIR test results. The addition of curcumin increased the mechanical properties slightly without changing the thermal stability of the PLA film. The composite film also exhibits excellent UV-barrier properties without much-sacrificing transparency of the PLA film. The water vapor permeability (WVP) and water contact angle (WCA) of the PLA film were slightly increased by the addition of curcumin but were not statistically significant (p > .05). The PLA/curcumin composite film also showed excellent antioxidant and some antibacterial activity. The functional PLA/curcumin composite films with improved physical and functional properties can be used in active food packaging applications.


Wide-field fluorescence lifetime imaging of neuron spiking and subthreshold activity in vivo.
The development of voltage-sensitive fluorescent probes suggests fluorescence lifetime as a promising readout for electrical activity in biological systems. Existing approaches fail to achieve the speed and sensitivity required for voltage imaging in neuroscience applications. We demonstrated that wide-field electro-optic fluorescence lifetime imaging microscopy (EO-FLIM) allows lifetime imaging at kilohertz frame-acquisition rates, spatially resolving action potential propagation and subthreshold neural activity in live adult Drosophila. Lifetime resolutions of <5 picoseconds at 1 kilohertz were achieved for single-cell voltage recordings. Lifetime readout is limited by photon shot noise, and the method provides strong rejection of motion artifacts and technical noise sources. Recordings revealed local transmembrane depolarizations, two types of spikes with distinct fluorescence lifetimes, and phase locking of spikes to an external mechanical stimulus.


Spectroscopic characterization of 2-amino-N-hexadecyl-benzamide (AHBA), a new fluorescence probe for membranes.
We report the results of investigation on the spectroscopic properties of a new fluorescent lipophylic probe. The fluorophore o-aminobenzoic acid was covalently bound to the acyl chain hexadecylamine, producing the compound 2-amino-N-hexadecyl-benzamide. The behavior of the probe was dependent on the polarity of the medium: absorption and emission spectral position, quantum yield and lifetime decay indicate distinct behavior in water compared to ethanol and cyclohexane. The probe dissolves in the organic solvents, as indicated by the very low value of steady state fluorescence anisotropy and the short rotational correlation times obtained from fluorescence anisotropy decay measurements. On the other hand, the probe has low solubility in water, leading to the formation of aggregates in aqueous medium. The complex absorption spectrum in water was interpreted as originating from different forms of aggregation, as deduced from the wavelength dependence of anisotropy parameters. The probe interacts with surfactants in pre-micellar and micellar forms, as observed in experiments in the presence of sodium n-dodecylsulphate (SDS), n-cetyltrimethylammonium bromide (CTAB); 3-(dodecyl-dimethylammonium) propane-1-sulphonate (DPS) and 3-(hexadecyl-dimethylammonium) propane-1-sulphonate (HPS), and with vesicles of the phospholipid dimiristoyl-phosphatidylcholine (DMPC). The results demonstrate that AHBA is able to monitor properties like surface electric potential and phase transition of micelles and vesicles.


Rice (Oryza sativa L.) inhibits growth and induces differentiation of human leukemic U937 cells through activation of peripheral blood mononuclear cells.
Rice (Oryza sativa L.) is a staple food worldwide for centuries. In this study, the growth-inhibiting and immunopotentiating effects of commonly used rice were examined. The growth of human leukemic U937 cells was significantly inhibited by the peripheral blood mononuclear cell-conditioned medium (MNC-CM) derived from water extracts of Japonica rice milled Taiwan 9 (MT9) and brown Taiwan 9 (BT9). Furthermore, these MNC-CMs induced differentiation of U937 cells into mature monocytes/macrophages expressing superoxide-producing and phagocytic activity. The amounts of tumor necrosis factor-alpha and interferon-gamma in MNC-CMs prepared with MT9 and BT9 were greater than normal MNC-CM. However, growth of U937 cells was not inhibited by normal MNC-CM or rice extracts alone. The possible active components of MT9 and BT9, other than PHA-like glycoproteins and heat-sensitive proteins and lipopolysaccharides, remain to be determined. Our results demonstrate that MT9 and BT9 can inhibit growth and induce differentiation of leukemic U937 cells through activation of human peripheral blood MNC in vitro. These two types of rice as energy-providing food could be biological response modifiers for augmenting anti-leukemia immunity.


Efficacy of tonsillectomy and adenoidectomy as an outpatient procedure: a preliminary report.
One of the recent trends in medical practice has been the use of ambulatory surgery for a substantial number of surgical procedures. A prospective evaluation of tonsillectomy and tonsillectomy with adenoidectomy as outpatient procedures at the Children's Hospital Medical Center in Cincinnati, OH, is reported. Patients who were felt to be inappropriate candidates for adenotonsillectomies as outpatients included patients under 3 years of age, patients who lived more than one hour from the hospital and patients who demonstrated obstructive sleep apnea or who had other significant medical problems. A review of this 9-month experience indicates that outpatient surgery for adenotonsillectomy is both safe and cost-effective in most circumstances. In an analysis of complications requiring readmission to the hospital (bleeding, dehydration, poor social situation), patients who had their original surgery performed on an ambulatory basis had no more complications than patients who were hospitalized following their surgery. Excluding the professional fees for the surgeon and anesthesiologist, a savings of approximately 50% can be expected from the performance of a tonsillectomy and adenoidectomy on an outpatient basis.


Freeze-fracture study of the lateral-line canal organ of the Japanese sea eel, Lincozymba nystromi.
Specializations of apical surfaces of hair cells, supporting cells and marginal cells in the lateral-line canal organ of Japanese sea eel, Lincozymba nystromi, were examined with a freeze-fracture technique. Apical surfaces of hair cells have a lower density of intramembrane particles (IMP) than those of the surrounding supporting cells. Density of IMP on the stereocilia is almost the same as that on the apical surface of hair cells. Junctions between hair and supporting cells were tighter than those between two supporting cells; those between supporting and marginal cells were tighter than those between hair and supporting cells, and those between two marginal cells were the tightest in the lateral-line canal organ.


An absolute requirement for P-selectin in ischemia/reperfusion-induced leukocyte recruitment in cremaster muscle.
To systematically examine a role for P-selectin in a model of striated muscle ischemia/reperfusion (I/R). Ischemia was induced in the cremaster muscle of mice by occluding the main feeding arteriole for 30 minutes. Blood flow was then restored to allow for 60 minutes of reperfusion and leukocyte kinetics were assessed during the control period (before I/R) and at 5, 30, and 60 minutes of reperfusion. To study a role for P-selectin in this model, three different approaches were used: Wild-type animals received fucoidin (10 mg/kg, i.v.), an anti-P-selectin antibody (RB40.34; 20 mg/animal, i.v.) at 25 minutes of ischemia, or I/R was induced in P-selectin-deficient mice. Ischemia/reperfusion induced a rapid and significant increase in leukocyte rolling, adhesion, and emigration in wild-type mice. The I/R-induced increase in leukocyte rolling was transient, inasmuch as it was reduced by approximately 50% at 30 minutes of reperfusion, and returned to control levels by 60 minutes. Both fucoidin and an anti-P-selectin antibody completely prevented the I/R-induced increase in leukocyte rolling. The P-selectin-deficient animals exhibited absolutely no baseline leukocyte rolling, adhesion, or emigration. Furthermore, I/R did not induce any increase in leukocyte recruitment in the P-selectin-deficient animals over the first 60 minutes of reperfusion. The results from this study clearly illustrate that P-selectin is absolutely critical in both baseline and I/R-induced leukocyte infiltration in the murine-striated muscle.


Genetic predisposition to adverse events in Chinese children aged 3-24 months after diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccination.
Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. From July 2019 to June 2020, we performed a case-control study among children aged 3-24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44-36.58, P = 0.0165). Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.


Assessment of blood platelets as a model for CNS response: comparative effects of caffeine on 5-HT uptake and release mechanisms in rat platelets and rat brain serotonin neurons.
We have previously reported that caffeine significantly enhanced 5-HT uptake and reduced 5-HT release from crude synaptosomal fractions obtained from rat cerebral cortex and from midbrain raphe region. Blood platelets, as reported by many laboratories and also demonstrated in our own labs, have a very active mechanism for 5-HT uptake and storage. In this regard platelets bear a high degree of similarity to brain serotonin neurons. The present experiments were, therefore, carried out to investigate the effects of caffeine on 5-HT uptake and release from rat platelets in an attempt to assess the possibility of using platelets as a model for studying the CNS effects of caffeine. Platelet rich plasma was prepared from the trunk blood of decapitated rats. Effects of caffeine were investigated at 10(-7), 10(-6), 10(-5) and 10(-4)M, on both the high affinity 3H-5-HT uptake and the spontaneous 5-HT release from 3H-5-HT preloaded platelets. The results show that caffeine did not change 5-HT uptake into platelets. In brain synaptosomes the same concentration of caffeine, however, increased 5-HT uptake dose-dependently. The results also revealed that caffeine increased 5-HT release from rat platelets in a concentration-dependent manner. The concentrations 10(-6), 10(-5), and 10(-4)M increased release significantly compared to control. This finding is also in contrast to that observed in synaptosomes of brain serotonin neurons where caffeine decreased 5-HT release. It is concluded, therefore, that the rat blood platelet is not a suitable model for studying these CNS actions of caffeine. Furthermore, our observations imply that rat platelet serotonin uptake and release mechanisms are not identical to those mechanisms in brain serotonin neurons.


Endometriosis of sigmoid colon mimicking malignant tumor diagnosed by intraoperative imprint cytology.
A case of endometriosis of the sigmoid colon on imprint cytology from an intraoperative biopsy is discussed. Cytologic specimens showed sheets or tubular epithelial clusters and stromal fragments. The epithelial cell nuclei were small and round to ovoid with finely granular chromatin and inconspicuous nucleoli. The background showed a few scattered spindle-type stromal cells without pigment-laden histiocytes. A definitive diagnosis of endometriosis can be based on cytology, provided that the cytologic findings are interpreted in the appropriate clinical context.


Electrophilic terminal arsinidene-iron(0) complexes with a two-coordinated arsenic atom.
The first terminal arsinidene complexes [{(NHC)C(Ph)}As]Fe(CO)4 (NHC = IPr = C{(NDipp)CH}25, Me-IPr = C{(NDipp)CMe}26; Dipp = 2,6-iPr2C6H3) with a two-coordinated arsenic atom have been reported as crystalline solids. Calculations suggest that 5 and 6 are electrophilic, which has been demonstrated by the reaction of 5 with an NHC nucleophile (IMe4), affording the Lewis adduct [{(IPr)C(Ph)}As(IMe4)]Fe(CO)4 (7) (IMe4 = C(NMeCMe)2).


A C-di-GMP-proflavine-hemin supramolecular complex has peroxidase activity--implication for a simple colorimetric detection.
Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) and hence provides simple colorimetric detection of c-di-GMP at low micromolar concentrations.


Emission enhanced fluorometric biosensor by functionalized carbon polymer dots for glutathione detection in human real samples and molecular logic gate operation.
Glutathione (GSH), an active peptide, plays pivotal roles in many physiological processes and detection of GSH inside of human body is of great importance for the playing of its biological effects. Here silver-phosphorus co-doped carbonized polymer dots (Ag@PCPDs) were prepared via solvothermal treatment of citric acid and phytic acid in the presence of Ag+ for GSH determination. The physicochemical and optical performance of the Ag@PCPDs were characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FT-IR), X-ray powder diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), fluorescence spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy analyses. The prepared Ag@PCPDs have outstanding water solubility with high monodispersity (7.81 ± 0.31 nm) and exhibited excellent optical properties with excitation-dependent emission, high photostability, pH, and ionic strength tolerance. An optimized excitation at 358 nm, the Ag@PCPDs showed strong photoluminescent (PL) emission at 456 nm with a PL quantum yield (QYs) of 15.6%. Furthermore, the Ag@PCPDs were used as a PL sensing platform for detection GSH in a linear range of 0-200 μM with a low limit of detection at 0.68 μM. In addition, the proposed system can construct molecular logic gates with GSH and Fe3+ ions as the chemical inputs and PL emissions as the output. And the Ag@PCPDs were successfully used for GSH determination in real samples resulting in high sensitivity and satisfactory recoveries (92.81--107.45%). More importantly, the Ag@PCPDs showed low cytotoxicity at 500 μg/mL and superior cell imaging capability in HeLa cells, which offer a new path for detection and categorization of GSH in biomedical applications.


On the estimation of refractory period.
The refractory period concept is exploited in many neurophysiological studies as a part of developed methods. Computations connected to these methods are influenced by the estimated value of refractory period. In this article, parametric and nonparametric refractory period estimation methods (minimum, maximum likelihood estimate, minimum risk estimate, etc.) are compared for three neuronal models. The results acquired from simulated data illustrate both accuracy and bias of different techniques. Experimental data are also investigated to show the limitations of the methods discussed.


A case of unilateral optic disc swelling with chronic active Epstein-Barr virus infection.
Ocular complications of chronic active Epstein-Barr virus (EBV) infection have rarely been reported and are usually associated with systemic symptoms. We described a 17-year-old boy with unilateral optic disc swelling without any systemic symptoms at the initial onset. Antibody titers to EBV were markedly elevated. Treatment with immunosuppressants and corticosteroids dramatically relieved all his symptoms, including unilateral optic swelling and visual field abnormalities.


Are the cochrane group registers comprehensive? A case study of Japanese psychiatry trials.
Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. The Japanese register contained 56 reports of randomized controlled trials (RCTs) of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect.


Functional and phenotypic analysis of isolated human Langerhans cells and indeterminate cells.
In the mixed skin cell lymphocyte culture reaction (MSLR), epidermal cells induce the proliferation in vitro of peripheral blood lymphocytes. Using monoclonal antibodies (MCAB) OKT6 specific for Langerhans cells among epidermal cells and an anti HLA-Dr, we analysed which epidermal cells are necessary in MSLR in man. Inhibition and reduction of the proliferative responses in MSLR conducted respectively with 'anti HLA-Dr and complement' and 'OKT6 and complement'-pretreated epidermal cells suggested that not only Langerhans cells but also other HLA-Dr bearing cells play a major role. Immuno-electron microscopic studies of either HLA-Dr (+) or OKT6 (+) enriched and depleted epidermal cells suspensions: (I) were well correlated with results in MSLR; (2) indicated that Langerhans cells express both T6 and HLA-Dr determinants while indeterminate cells express only the HLA-Dr. No other epidermal cells were found to be either OKT6 or HLA-Dr (+). The data strongly suggest that not only Langerhans cells but also OKT6 (-) HLA-Dr (+) indeterminate cells play a major role in lympho-epidermal interactions.


The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile.
The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]-PBR28 positron-emission tomography imaging. This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty-five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini-Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron-emission tomography with detailed clinical characterization of delirium, cognition, and functional status.


Female permanent contraception trends and updates.
Permanent contraception remains one of the most popular methods of contraception worldwide. This article has reviewed recent literature related to demographic characteristics of users, prevalence of use and trends over time, surgical techniques, and barriers to obtain the procedure. We have emphasized the patient's perspective as a key element of choosing permanent contraception. This review has incorporated sections on salpingectomy, hysteroscopy, unmet need, impact of policies at religiously affiliated institutions, and reproductive coercion.


Availability of pharmaceuticals in sub-Saharan Africa: roles of the public, private and church mission sectors.
Although the availability of pharmaceuticals is critical for both curative and preventive health care, drugs are, at best, sporadically available in governmental facilities in sub-Saharan Africa. The religious missions and private sectors are more successful than the public sector in obtaining and distributing drugs. The public sector operates under a myriad of constraints inherent in a bureaucracy; the religious missions have the advantages of better management and access to foreign currency; the private sector is innately efficient. Donor assistance to increase the availability of drugs in the public sector has included support for revolving drug funds, national drug services, the improvement of management techniques, and the local production of pharmaceuticals. None of these interventions has been notably successful. In 1987, UNICEF presented The Bamako Initiative--a proposal to launch an internationally-financed fund for essential drugs for sub-Saharan Africa. However, the proposal is unrealistic in anticipating that the requisite resources and/or hard currency can be raised to support the proposal. As the private sector is a more efficient distributor, it is recommended that the private sector be given responsibility for the distribution of drugs. Nonetheless, some governmental controls will be necessary to ensure that essential drugs are available at the least cost to the consumer.


A renal biopsy study of lupus nephropathy in the United States and Korea.
A comparative study was made using renal biopsy specimens obtained from US and Korean patients with lupus nephropathy. Significant differences were observed in the morphologic distribution and activity of the disease. Korean patients exhibited a higher frequency of World Health Organization class IV lupus nephropathy (77.8%) than black (47.2%) or white (42.1%) US patients (P less than 0.025, P less than 0.05, respectively), and a higher inflammatory intensity index (P less than 0.045) than US patients. Korean patients also showed a significantly lower frequency of WHO class III nephropathy (P less than 0.05). No significant morphologic differences were seen between the US white and black patient populations. These data suggest that the Korean patients had a more active and potentially more fulminating disease than the US patients. Whether differences in genetic and external causative factors play a role in the observed differences in renal histopathology among these groups remains to be clarified.


Glial Glutamine Homeostasis in Health and Disease.
Glutamine is an essential cerebral metabolite. Several critical brain processes are directly linked to glutamine, including ammonia homeostasis, energy metabolism and neurotransmitter recycling. Astrocytes synthesize and release large quantities of glutamine, which is taken up by neurons to replenish the glutamate and GABA neurotransmitter pools. Astrocyte glutamine hereby sustains the glutamate/GABA-glutamine cycle, synaptic transmission and general brain function. Cerebral glutamine homeostasis is linked to the metabolic coupling of neurons and astrocytes, and relies on multiple cellular processes, including TCA cycle function, synaptic transmission and neurotransmitter uptake. Dysregulations of processes related to glutamine homeostasis are associated with several neurological diseases and may mediate excitotoxicity and neurodegeneration. In particular, diminished astrocyte glutamine synthesis is a common neuropathological component, depriving neurons of an essential metabolic substrate and precursor for neurotransmitter synthesis, hereby leading to synaptic dysfunction. While astrocyte glutamine synthesis is quantitatively dominant in the brain, oligodendrocyte-derived glutamine may serve important functions in white matter structures. In this review, the crucial roles of glial glutamine homeostasis in the healthy and diseased brain are discussed. First, we provide an overview of cellular recycling, transport, synthesis and metabolism of glutamine in the brain. These cellular aspects are subsequently discussed in relation to pathological glutamine homeostasis of hepatic encephalopathy, epilepsy, Alzheimer's disease, Huntington's disease and amyotrophic lateral sclerosis. Further studies on the multifaceted roles of cerebral glutamine will not only increase our understanding of the metabolic collaboration between brain cells, but may also aid to reveal much needed therapeutic targets of several neurological pathologies.


[The study of proliferation of cells at the invasive tumor front of squamous cell carcinoma of tongue].
To evaluate the value of the invasive front grading (IFG), the proliferative activity of cells at the invasive tumor front (ITF) of squamous cell carcinoma (SCC) of tongue. All the tumors were graded using IFG grading. The expression of PCNA, Ki67 and staining and measurement of AgNOR number were evaluated at the ITF and the other parts of the same tumor. The expression of PCNA (P < 0.001), Ki67 (P < 0.001), AgNOR number (P < 0.001) at the ITF were higher than those of other parts. The IFG score was significantly correlated with the expression of PCNA (P < 0.05), AgNOR number (P < 0.01) at the ITF. The complete IFG score (P < 0.01) was significant in both univariate and multivariate cox analysis; the AgNOR number at the ITF (P < 0.05) was only significant in univariate analysis (P < 0.05). The ITF of SCCs of tongue differentiate poorer than the other parts and is active in proliferation. The complete IFG score and the AgNOR number at the ITF could be a valuable indication to predict the prognosis of SCCs of tongue.


Application of an objective method for localizing bilateral cortical FDG PET abnormalities to guide the resection of epileptic foci.
In order to improve the objective localization of bilateral cortical abnormalities in positron emission tomography (PET) image volumes, we developed a new three-dimensional image processing technique. The accuracy of this approach with respect to invasive subdural electroencephalography (EEG) data was assessed in a group of children with neocortical epilepsy. Glucose PET image volumes were obtained from 12 epileptic children (mean age 5.2 +/- 4.3 years). Bilateral cortical areas of abnormal glucose metabolism were objectively determined using two conditional criteria assessed against a normal database. The normal database was derived from a group of 15 adult controls (mean age 27.6 years). The spatial relationship between seizure onset electrodes and PET abnormalities was assessed using a conventional receiver operating characteristic (ROC) analysis as well as using a newly defined spatial proximity index (SPI), which characterizes the association between adjacent, but not coincident, abnormalities. ROC analysis at the 2 standard deviation (SD) threshold, revealed an accuracy of 65% to detect seizure onset areas with a sensitivity of 64 +/- 17% and a specificity of 66 +/- 24%. Sensitivity decreased to 46 +/- 24% at the 3-SD threshold with a specificity of 80 +/- 21% (accuracy 75%). The average value for the SPI was determined as 3.82 +/- 1.65 which was 20% lower than the SPI value calculated using a simple in-plane two-dimensional asymmetry between homotopic cortical segments (4.52 +/- 3.82). The presented image processing technique improves localization of cortical abnormalities and provides valuable imaging clues for placement of subdural EEG grids prior to surgical resection.


Metabolic engineering of Escherichia coli for biosynthesis of hyaluronic acid.
Engineering of hyaluronic acid (HA) biosynthetic pathway in recombinant Escherichia coli as production host is reported in this work. A hyaluronic acid synthase (HAS) gene, sphasA, from Sreptococcus pyogenes with the start codon gtg to atg mutant, was expressed in recombinant E. coli with or without the genes ugd, galF and glmU, which are analogs of hasB, hasC and hasD from Streptococcus, respectively, encoding UDP-glucose 6-dehygrogenase, Glucose-1-P uridyltransferase, and N-acetyl glucosamine uridyltransferase enzymes in the HA biosynthetic pathway. The single, double and triple organized artificial operons of sphasA, ugd, galF and glmU were designed and constructed using the inducible plasmid backbone of pMBAD. Only the triple expression recombinant, Top10/pMBAD-spABC, generated a relatively high titer of HA (approximately 48 mg/l at 48 h), indicating that both of the enzymes encoded by ugd and galF are essential for HA biosynthesis. A new gene of ssehasA with identical protein sequence of seHAS from Streptococcus equisimilis, was artificially synthesized after substituting all of the rare codons in the natural sehasA. The HA titer at 24 h flask culture increased to approximately 190 mg/l in sseAB and 160 mg/l in sseABC, respectively. Sorbitol could be used as another carbon source for HA accumulation, and the metabolic pathway for HA synthesis in a recombinant E. coli was presented. The concentration of Mg(2+) cofactor of HA synthase was optimized and a cell growth inhibition phenomenon was observed during HA accumulation. Molecular weight (MW) measurements revealed that the mean MW of HA produced from the recombinant E. coli under different conditions ranges from approximately 3.5x10(5) to 1.9x10(6)Da, indicating that the recombinant E. coli can be used as a potential host candidate for industrial production of HA.


How to Construct a Mixed Methods Research Design.
This article provides researchers with knowledge of how to design a high quality mixed methods research study. To design a mixed study, researchers must understand and carefully consider each of the dimensions of mixed methods design, and always keep an eye on the issue of validity. We explain the seven major design dimensions: purpose, theoretical drive, timing (simultaneity and dependency), point of integration, typological versus interactive design approaches, planned versus emergent design, and design complexity. There also are multiple secondary dimensions that need to be considered during the design process. We explain ten secondary dimensions of design to be considered for each research study. We also provide two case studies showing how the mixed designs were constructed.


Antenatal exposure to doxylamine succinate and dicyclomine hydrochloride (Benedectin) in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score.
In a prospective cohort study of 20, 282 gravidas and their offspring, congenital malformation rates were similar in the children of over 1,000 women exposed and those not exposed to two components of Bendectin (doxylamine succinate and dicyclomine hydrochloride) during the first four lunar months of pregnancy. In a cohort reduced to 41,337 mother-child pairs for technical reasons, mean birth weight and perinatal mortality rates were similar according to exposure or nonexposure to either drug, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter these findings.


Parallelized microscale fed-batch cultivation in online-monitored microtiter plates: implications of media composition and feed strategies for process design and performance.
Limited throughput represents a substantial drawback during bioprocess development. In recent years, several commercial microbioreactor systems have emerged featuring parallelized experimentation with optical monitoring. However, many devices remain limited to batch mode and do not represent the fed-batch strategy typically applied on an industrial scale. A workflow for 32-fold parallelized microscale cultivation of protein secreting Corynebacterium glutamicum in microtiter plates incorporating online monitoring, pH control and feeding was developed and validated. Critical interference of the essential media component protocatechuic acid with pH measurement was revealed, but was effectively resolved by 80% concentration reduction without affecting biological performance. Microfluidic pH control and feeding (pulsed, constant and exponential) were successfully implemented: Whereas pH control improved performance only slightly, feeding revealed a much higher optimization potential. Exponential feeding with µ = 0.1 h-1 resulted in the highest product titers. In contrast, other performance indicators such as biomass-specific or volumetric productivity resulted in different optimal feeding regimes.


Distribution of SCCmec-associated phenol-soluble modulin in staphylococci.
The recently described phenol-soluble modulin PSM-mec was detected in Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus fleuretti, Staphylococcus hominis, Staphylococcus pseudintermedius, Staphylococcus saprophyticus, Staphylococcus simulans and Staphylococcus vitulinus from different hosts (humans, goats, dogs, cats, pigs, cattle and turkeys). It was identified in isolates harbouring SCCmec types II, IIA, IIB, IID, III, VIII and in some irregular or truncated elements.


Observation of a topological nodal surface and its surface-state arcs in an artificial acoustic crystal.
Three-dimensional (3D) gapless topological phases can be classified by the dimensionality of the band degeneracies, including zero-dimensional (0D) nodal points, one-dimensional (1D) nodal lines, and two-dimensional (2D) nodal surfaces. Both nodal points and nodal lines have been realized recently in photonics and acoustics. However, a nodal surface has never been observed in any classical-wave system. Here, we report on the experimental observation of a twofold symmetry-enforced nodal surface in a 3D chiral acoustic crystal. In particular, the demonstrated nodal surface carries a topological charge of 2, constituting the first realization of a higher-dimensional topologically-charged band degeneracy. Using direct acoustic field measurements, we observe the projected nodal surface and its Fermi-arc-like surface states and demonstrate topologically-induced robustness of the surface states against disorders. This discovery of a higher-dimensional topologically-charged band degeneracy paves the way toward further explorations of the physics and applications of new topological semimetal phases.


Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER).
Carbonyl reductase 1 (CBR1) reduces the anticancer anthracyclines doxorubicin and daunorubicin into the cardiotoxic metabolites doxorubicinol and daunorubicinol. We evaluated whether the cardioprotectant monoHER inhibits the activity of polymorphic CBR1. We performed enzyme kinetic studies with monoHER, CBR1 (CBR1 V88 and CBR1 I88) and anthracycline substrates. We also characterized CBR1 inhibition by the related flavonoids triHER and quercetin. MonoHER inhibited the activity of CBR1 V88 and CBR1 I88 in a concentration-dependent manner. The IC(50) values of monoHER were lower for CBR1 I88 compared to CBR1 V88 for the substrates daunorubicin and doxorubicin (daunorubicin, IC(50)-CBR1 I88 = 164 microM vs. IC(50)-CBR1 V88 = 219 microM; doxorubicin, IC(50)-CBR1 I88 = 37 microM vs. IC(50)-CBR1 V88 = 59 microM; p < 0.001). Similarly, the flavonoids triHER and quercetin exhibited lower IC(50) values for CBR1 I88 compared to CBR1 V88 (p < 0.001). MonoHER acted as a competitive CBR1 inhibitor when using daunorubicin as a substrate Ki = 45 +/- 18 microM. MonoHER acted as an uncompetitive CBR1 inhibitor for the small quinone substrate menadione Ki = 33 +/- 17 microM. The cardioprotectant monoHER inhibits CBR1 activity. CBR1 V88I genotype status and the type of anthracycline substrate dictate the inhibition of CBR1 activity.


Hand eczema in glove-wearing patients.
Allergic contact dermatitis to gloves is mostly induced by rubber accelerators. The European baseline series (EBS) appears insufficient to detect glove allergy. Since 2017, it is recommended to use the European rubber series (ERS) and to test the patients' own gloves. To investigate the clinical profile of glove-wearing patients with hand eczema (HE) and to evaluate their sensitisation profile to glove allergens and the value of testing the patients' own gloves. We conducted a French multicentre study of patients evaluated for HE between 2018 and 2020 and tested with the EBS, the ERS and their own gloves in patch tests and semi-open (SO) tests. A total of 279 patients were included; 32.6% of patients had positive tests to their own gloves or to glove allergens. Almost 45% of the sensitisations to glove allergens were detected only by the ERS. Among the patients tested both in patch tests and SO tests with their own gloves with positive results, 28% had positive SO tests only. Polyvinylchloride (PVC) gloves were positive in four patients. Our series confirms the need to test the ERS. All the patients' gloves must also be tested including PVC gloves. SO tests with gloves are useful as a complement to patch tests.


The association between the use of shift schedule evaluation tool with ergonomics recommendations and occupational injuries: A 4-year prospective cohort study among healthcare workers.
This study aimed to find out whether utilizing a shift schedule evaluation tool with ergonomics recommendations for working hours has favorable effects on the incidence of occupational injuries. This 4-year prospective cohort study (2015-2018) consisted of a dynamic cohort of healthcare shift workers (N=29 237) from ten hospital districts and six cities in Finland. Working hour characteristics and occupational injuries were measured with daily registry data. Multilevel generalized linear model was used for the analyses, and the estimates were controlled for hierarchical structure of the data and confounders. Ward heads of the cities used the shift schedule evaluation tool 3.2 times more often than ward heads of the hospital districts. Overall incidence of workplace and commuting injuries did not differ between users and non-users of the evaluation tool. The incidence of dislocations, sprains, and strains was lower in the users than non-users [adjusted odds ratio (OR) 0.88, 95% confidence interval (CI) 0.78-0.99]. Approximately 13% of this association was mediated by increase in realized shift wishes and 10% by increase in single days off. In subgroup analyses, the incidence of workplace injury (OR 0.83, 95% CI 0.69-0.99), and among types of injuries, the incidence of dislocations, sprains, and strains (OR 0.69, 95% CI 0.55-0.85) and falling, slipping, tripping, or overturning (OR 0.75, 95% CI 0.58-0.99) were lower in users than non-users among employees of the cities, but no association was found among employees of the hospital districts. The use of ergonomics recommendations for working hours is associated with a reduced risk of occupational injuries.


BLU-DAT: a new reliable and accurate arthrometer for measuring anterior knee laxity.
Although many arthrometers have been developed to assess anterior knee laxity, reliability and diagnostic accuracy of these devices are still debated. The aim of the present study was to evaluate the validity of a new arthrometer in the outpatient setting, with the hypothesis that it had good validity in terms of reliability and diagnostic accuracy. Seventy-eight subjects (39 with ACL injury and 39 with normal ACL) were tested. ATT was assessed by means of the Lachman test at 30° of flexion with a new testing device (BLU-DAT) under three different loading conditions: 7 kg (69 N), 9 kg (88 N) and maximum (MMT). The tests were performed on both knees to obtain SSD. In the ACL injury group, the tests were performed by two examiners and one of them repeated a second test series. Inter- and intra-observer reliability were assessed with the intraclass correlation coefficients (ICCs) for the average SSD measures. In the normal-ACL group, the analysis was performed with the same testing setup. Side-to-side difference measures of the two groups at every loading condition were compared by Student's t test. Data of test series were dichotomized based on the threshold value of 3-mm SSD as pathological ATT and 2 × 2 contingency tables were used to assess diagnostic accuracy. The ICCs for intra-observer reliability at 7-kg (69 N), 9-kg (88 N) and MMT measurements were 0.781, 0.855 and 0.913, respectively. The ICC for inter-observer reliability at 7-kg (69 N), 9-kg (88 N) and MMT measurements were 0.701, 0.845 and 0.834, respectively. Comparison between the two groups showed a significant mean difference ranging from 3.4 mm for 7-kg (69 N) load to 4.6 mm for MMT. Overall accuracy ranged from 84.6% for 7-kg load to 98.7% for MMT. The BLU-DAT has proven to be an instrument with good intra- and inter-observer reliability and very good accuracy in the diagnosis of ACL injuries in the outpatient setting. So, the BLU-DAT can be a new useful tool in everyday clinical practice to assist in the diagnosis of ACL injury. II.


Mechanisms of seizure-induced 'transcriptional channelopathy' of hyperpolarization-activated cyclic nucleotide gated (HCN) channels.
Epilepsy may result from abnormal function of ion channels, such as those caused by genetic mutations. Recently, pathological alterations of the expression or localization of normal channels have been implicated in epilepsy generation, and termed 'acquired channelopathies'. Altered expression levels of the HCN channels - that conduct the hyperpolarization-activated current, I(h) - have been demonstrated in hippocampus of patients with severe temporal lobe epilepsy as well as in animal models of temporal lobe and absence epilepsies. Here we probe the mechanisms for the altered expression of HCN channels which is provoked by seizures. In organotypic hippocampal slice cultures, seizure-like events selectively reduced HCN type 1 channel expression and increased HCN2 mRNA levels, as occurs in vivo. The mechanisms for HCN1 reduction involved Ca(2+)-permeable AMPA receptor-mediated Ca(2+) influx, and subsequent activation of Ca(2+)/calmodulin-dependent protein kinase II. In contrast, upregulation of HCN2 expression was independent of these processes. The data demonstrate an orchestrated program for seizure-evoked transcriptional channelopathy involving the HCN channels that may contribute to certain epilepsies.


Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus.
Monocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D. 60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg-1000 mg) combined with either glimepiride (1 mg-2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed. Mean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found. Patients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).


[Ligament reconstruction in extensor tendon dislocation].
Stabile recentering the extensor tendon over the top of the head of the metacarpal to restore the exact tension and the direction. Dislocation of the extensor tendon at the metacarpophalangeal (MP) joint with functional disabilities of the fingers. Severe osteoarthritis of the MP joint. Accompanying injuries of collateral ligaments. Fibrosis of the MP joint or contractures of the intrinsic muscles. Curved 8 cm skin incision at distal metacarpal, MP joint, and proximal phalanx. A distally pedicled central tendon strip from the extensor digitorum communis (EDC) tendon is removed. Centralization of the tendon by reconstructing the sagittal ligament and the proximal part of the extensor hood. The tendon strip is wrapped around the tendon of the interossous muscle. Immobilization of the MP joint in 30° flexion with free proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints for 4 weeks. Full fist after 5 weeks. In all 16 patients good or very good results were achieved. There were no recurrences of tendon dislocations, no MP joint contractures, and only a few minor extensor tendon adhesions.


[Effect of selenium on the enzymatic transformation of retinal and vitamin A assimilation].
The effect of sodium selenite on the enzymatic oxidation of retinal in vitro and vitamin A accumulation in the rat liver was examined. Selenium as sodium selenite at concentrations of 0.5--2.5 microgram/ml inhibited significantly (40--45%) the enzymatic irreversible oxidation of retinal. Dietary supplements of sodium selenite at a dose of 50--250 microgram/kg body weight caused an almost two-fold increase of the vitamin A content in the rat liver as compared with the controls that were given no selenium.


Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia.
The amyloid beta-peptide (Abeta) activates microglia and promotes the generation of cytokines and oxygen species, including nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha), which can be either neurotoxic or neuroprotective. We show that neuron death in cocultures of rat cortical microglia and neurons activated by lipopolysaccharide (LPS) or Abeta1-42 plus interferon gamma (IFNgamma) is caused by short-lived diffusible molecules and follows the generation of superoxide and/or peroxynitrite as determined by electron paramagnetic spectroscopy. Neurotoxicity induced by LPS or Abeta1-42 plus IFNgamma is blocked by inhibitors of NO synthesis and by the peroxynitrite (ONOO-) decomposition catalysts FeTMPyP [5,10,15,20-tetrakis(n-methyl-4'-pyridyl)porphinato iron (III) chloride] and FeTPPS [5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride] but not by the TNF-alpha inhibitor pentoxifylline. The specificity of FeTMPyP for ONOO- was confirmed by its ability to block the toxicity of a peroxynitrite donor but not of NO donors or of high levels of superoxide in a yeast mutant lacking superoxide dismutase 1. These results implicate peroxynitrite as a mediator of the toxicity of activated microglia, which may play a major role in Abeta1-42 neurotoxicity and Alzheimer's disease.


Subscale validation of the neuropsychiatric inventory questionnaire: comparison of Alzheimer's disease neuroimaging initiative and national Alzheimer's coordinating center cohorts.
Neuropsychiatric symptoms are prevalent in mild cognitive impairment (MCI) and Alzheimer disease (AD) and commonly measured using the Neuropsychiatric Inventory (NPI). Based on existing exploratory literature, we report preliminary validation of three NPI Questionnaire (NPI-Q-10) subscales that measure clinically meaningful symptom clusters. Cross-sectional results for three subscales (NPI-Q-4-Frontal, NPI-Q-4-Agitation/Aggression, NPI-Q-3-Mood) in amnestic MCI and AD dementia cases from the National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) databases were analyzed using confirmatory unrotated principal component analysis. ADNI contributed 103 MCI, 90 MCI converters, and 112 AD dementia cases, whereas NACC contributed 1,042 MCI, 763 MCI converters, and 3,048 AD dementia cases. NACC had higher baseline mean age (75.7 versus 74.6), and more impaired mean scores (at month 24) on Mini-Mental State Exam (19.5 versus 22.4) and NPI-Q-10 (5.0 versus 4.3), and all NPI-Q subscales than ADNI. Medians were not different between cohorts for NPI-Q-4-Agitation/Aggression, and NPI-Q-3-Mood, however. Each item on all scales/subscales contributed variance in principal component analysis Pareto plots. All items in Factor (F) 1 for each scale/subscale projected in a positive direction on biplots (revealing coherence), whereas F2 and F3 items showed more spatial separation (revealing independence). There were remarkable similarities between cohorts for factor loadings and spatial patterns of item projections, although factor item identities varied somewhat, especially beyond F1. The similar pattern of results across two cohorts support validity of these subscales, which are worthy of further psychometric evaluation in MCI and AD patients and preliminary application in clinical settings.


The triple-negative (CD34-/HLA-DR-/CD11b-) profile rapidly and specifically identifies an acute promyelocytic leukemia.
The genetic testing to confirm or rule out an acute promyelocytic leukemia (APL) typically takes a minimum of 24-72 hours. Flow cytometric immunophenotyping (FCI) on the other hand provides rapid and objective information to differentiate APL from non-APL. FCI features, with single-tube 8-color combination using CD45, CD34, HAL-DR, CD11b, CD13, CD33, and CD117 and CD64, were compared for the 30 consecutive APL and 30 non-APL acute myeloid leukemia (AML) cases which morphologically mimicked an APL. The diagnosis was confirmed by cytogenetic or molecular genetic testing in the form of t (15:17) (q22; q21)/variant translocations or PML-RARA fusion transcript analysis. The APL cells lacked CD34, HLA-DR, and CD11b in 90%, 90%, and 93.3% cases, respectively. Myeloid antigens such as CD33, CD13, CD117, and CD64 were expressed in 96.7%, 96.7%, 76.7%, and 70% cases, respectively. The dual negative profiles, CD34-/HLA-DR- or HLA-DR-/CD11b-, were noted in 90% and 93.3% cases. The triple-negative (CD34-/HLA-DR-/CD11b-) profile was noted in 90% of the cases. The sensitivity, specificity, and positive predictive value (PPV) of CD34-/HLA-DR- and HLA-DR-/CD11b- profiles for the diagnosis of APL were found to be 90%, 80% & 81.1% and 93.3%, 86.7%& 87.5%, respectively. Combining the above two profiles resulted in a triple-negative profile (CD34-, HLA-DR- and CD11b-), which had a better specificity (93.3%) and positive predictive value (93.1%), with similar sensitivity. FCI is a rapid and reliable modality for the diagnosis of an APL. The triple-negative profile (CD34-/HLA-DR-/CD11b-) rapidly and specifically identifies an APL case.


Place avoidance learning and stress-induced analgesia in the attacked mouse: role of endogenous opioids.
In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.


Human health benefits from livestock vaccination for brucellosis: case study.
To estimate the economic benefit, cost-effectiveness, and distribution of benefit of improving human health in Mongolia through the control of brucellosis by mass vaccination of livestock. Cost-effectiveness and economic benefit for human society and the agricultural sector of mass vaccination against brucellosis was modelled. The intervention consisted of a planned 10-year livestock mass vaccination campaign using Rev-1 livestock vaccine for small ruminants and S19 livestock vaccine for cattle. Cost-effectiveness, expressed as cost per disability-adjusted life year (DALY) averted, was the primary outcome. In a scenario of 52% reduction of brucellosis transmission between animals achieved by mass vaccination, a total of 49,027 DALYs could be averted. Estimated intervention costs were US$ 8.3 million, and the overall benefit was US$ 26.6 million. This results in a net present value of US$ 18.3 million and an average benefit-cost ratio for society of 3.2 (2.27-4.37). If the costs of the intervention were shared between the sectors in proportion to the benefit to each, the public health sector would contribute 11%, which gives a cost-effectiveness of US$ 19.1 per DALY averted (95% confidence interval 5.3-486.8). If private economic gain because of improved human health was included, the health sector should contribute 42% to the intervention costs and the cost-effectiveness would decrease to US$ 71.4 per DALY averted. If the costs of vaccination of livestock against brucellosis were allocated to all sectors in proportion to the benefits, the intervention might be profitable and cost effective for the agricultural and health sectors.


Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome.
Necropsy findings are reported for a case of Joubert syndrome (familiar aplasia of cerebellar vermis with episodic hyperpnea, abnormal eye-movements, ataxia and retardation). The findings consisted of an almost total aplasia of the cerebellar vermis; dysplasias and numerous heterotopias of cerebellar nuclei; an almost total absence of pyramidal decussation; and anomalies in the structure of the inferior olivary nuclei, the descending trigeminal tract, solitary fascicle and of the dorsal column nuclei. The lesion resembled the Dandy-Walker malformation or simple aplasia of the cerebellar vermis in some of its aspects, but there were numerous others to set it apart--at least tentatively--as a distinct nosologic entity.


Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects.
Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for "normal" subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.


Hypnosis in a treatment programme for alcoholism.
This is a report on a pilot study of the use of hypnosis in the treatment of alcoholism at an outpatient clinic. It describes the characteristic features of the sample of patients who seem to have responded to treatment and gives an account of the therapeutic programme.


Risks and indications of phenylbutazone: another look.
In 1984 an extensive review of phenylbutazone risks was undertaken by the Food and Drug Administration (FDA). Since that review, new recommendations for the drug's use have been published. Marketed in 1952, phenylbutazone has long been recognized as capable of inducing aplastic anemia. The risk of marrow depression is greatest in elderly females treated for over a month. Overall, the risk does not exceed that of many commonly used drugs (e.g., penicillin, which induces anaphylaxis). Nonetheless, phenylbutazone should not be a drug of first choice and should not be used for minor, self-limited conditions.


Prognostic and Therapeutic Role of CD15 and CD15s in Cancer.
CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These cancers include renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma. The biological role of CD15 is interaction with E-, L- and P-selectins (adhesion molecules), allowing for adhesion with endothelial cells. In this way, cancer cells start to interact with the endothelia of blood vessels and consequently move out from the blood flow to the surrounding tissues. Blockage of the antigen's function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibody-based therapies. CD15 may serve as a prognostic marker for patients and there are high hopes for its use in the immunotherapeutic treatment of tumours. CD15s is a sialyl derivative of CD15 that possesses its own unique characteristics. Its soluble form may act as a competitive inhibitor of the interaction of cancer cells with epithelial cells and thus disallow migration through the vessels. However, the prognostic relevance of CD15 and CD15s expression is very complex. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews its significance for clinical applications.


Effect of long term CPAP therapy on cardiac parameters assessed with cardiac MRI.
The obstructive sleep apnoea syndrome (OSAS) is a disorder with a high prevalence and is associated with an elevated cardiovascular risk and increased morbidity and mortality. For longitudinal studies and functional analysis cardiac MRI is regarded as the gold standard. Aim of this study was to evaluate the long-term effect of continuous positive airway pressure (CPAP) therapy on cardiac functional parameters with cardiac Magnetic Resonance Imaging (cMRI). 54 patients with OSAS (mean apnea hypopnea index-AHI: 31) were prospectively enrolled in this study and cMRI was performed before and after 7 months of CPAP therapy. Data were acquired on a 1.5 T MRI and right and left ventricular cardiac function were analysed. CPAP treatment was considered compliant when used ≥ 4 h per night. 24-h blood pressure was measured at baseline and follow up. 33 patients could be assigned to the compliance group. Left ventricular stroke volume (LV SV) and right ventricular ejection fraction (RV EF) improved significantly with CPAP therapy (LV SV from 93 ± 19 to 99 ± 20 ml, p = 0.02; RV EF from 50 ± 6 to 52 ± 6%, p = 0.04). All other cardiac parameters did not change significantly while mean systolic and diastolic blood pressure improved significantly (p < 0.01). 21 patients were assigned to the non-compliance group and were considered as a control group. There were no relevant differences in cardiac parameters between baseline and follow up examination in these patients. CPAP therapy seems to improve LV SV, RV EF, systolic and diastolic blood pressure in OSAS patients, but reproducibility of our results need to be confirmed in a larger patient population.


Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic octapeptide modified liposomes for targeting integrin α3 in triple-negative breast cancer.
A novel therapeutic strategy combining mTOR inhibitor rapamycin (RAPA) and doxorubicin (DOX)-loaded cyclic octapeptide liposomes for targeting integrin α3 was expected to combat the triple-negative breast cancer (TNBC). RAPA was loaded into PEG-PCL polymer micelles (M-RAPA) to realize solubilization. Flow cytometry analysis and laser confocal microscopy were used to evaluate the in vitro cellular uptake. The in vivo tumor targeting and bio-distribution were investigated by living fluorescence imaging. As the results, LXY modification significantly enhanced the cellular uptake of liposomal DOX in integrin α3 overexpressed TNBC cells (MDA-MB-231) in vitro and accordingly improved the tumor accumulation of liposomes in vivo. When used alone or in combination with LXY-LS-DOX, M-RAPA could greatly inhibit the expression of HIF-1α protein, which is always highly expressed in malignant cancers and involved in tumor angiogenesis, proliferation, therapeutic resistance and poor prognosis. Meanwhile, the improved efficacy of combined targeted therapy with LXY-LS-DOX and M-RAPA was demonstrated by the in vitro cytotoxicity against model TNBC cells and in vivo anti-tumor activity against mouse bearing TNBC model. These results suggested that the targeted combinational therapy based on LXY-LS-DOX and M-RAPA systems may provide a rational strategy to improve therapeutic outcomes of TNBC.


Enzyme immunoassay (Chlamydiazyme) for the detection of chlamydial antigen in endocervical specimens.
Endocervical swabs taken from 86 women were tested by the Chlamydiazyme enzyme immunoassay test to detect chlamydial antigens. Compared to cell culture, Chlamydiazyme was 100% sensitive and 90% specific. This test is suitable as alternative diagnostic method to cell culture and has the potential for automation.


Chitin based polyurethanes using hydroxyl terminated polybutadiene, Part II: morphological studies.
Chitin-hydroxyl terminated polybutadiene (HTPB) based polyurethane (PU) was prepared and structure of the pre-designed PU was confirmed using FT-IR spectrometer. The FT-IR analysis confirmed that the crosslinking density increased with increasing the chitin contents in the final PU. During the detailed FT-IR study, it was observed that tri-functional character of chitin is responsible for the formation of network structure. The scanning electron microscope (SEM) analysis also confirmed the cross-linked structure of the material. The amount of carbon, nitrogen and oxygen elements obtained from EDX-SEM microanalysis also supported the results. The resistance in solubility against the solvent also confirmed the crosslinking behavior of the prepared polyurethane.


Highly cohesive monolayers of lipid derivatives of colchicine: a dynamics study.
Monolayers of lipid derivatives of colchicine spread at the air--water interface reach the thermodynamic equilibrium over an abnormally long period of time. Dynamics of this equilibration and the behavior of the film during compression--decompression cycles are observed by fluorescence microscopy. The thermodynamically disfavored structures observed are unrelated to previously described unusual shapes in the liquid expanded-gas coexistence regions. The relation between the cholesterol-like effect of the colchicinoid moiety, its propensity to dimerize, and the high viscosity of the monolayer are discussed.


Semi-automated fabrication of customized ocular prosthesis with three-dimensional printing and sublimation transfer printing technology.
An ocular prosthesis is a custom-made polymeric insert that can be placed in an anophthalmic socket for cosmetic rehabilitation of patients who have lost their eyes. The process of creating such a custom-made ocular prosthesis is time-consuming and labor-intensive because it involves artistic work that is carried out manually. This paper proposes a novel semi-automated method for fabricating customized ocular prostheses using three-dimensional (3D) printing and sublimation transfer printing. In the proposed method, an impression mold of the patient's anophthalmic socket is first optically scanned using a 3D scanner to produce a 3D model. The ocular prosthesis is then produced via a digital light processing 3D printer using biocompatible photopolymer resin. Subsequently, an image of the iris and blood vessels of the eye is prepared by modifying a photographed image of the contralateral normal eye, and printed onto the 3D-printed ocular prosthesis using a dye sublimation transfer technique. Cytotoxicity assessments of the base material and fabricated ocular prosthesis indicate that there is no adverse effect on cellular viability and proliferation. The proposed method reduces the time and skill required to fabricate a customized ocular prosthesis, and is expected to provide patients with easier access to quality custom-made ocular prostheses.


Impact of AKI in Patients with Out-of-Hospital Cardiac Arrest Managed with VA ECMO.
AKI is associated with a high rate of mortality in patients managed with VA ECMO after out-of-hospital cardiac arrest.Therapeutic hypothermia is associated with hypokalemia and hypophosphatemia.During rewarming after hypothermia, hyperphosphatemia and hyperkalemia can develop. Electrolyte replacement should be carefully monitored.


Cigarette smoking behavioral distinctions between experimental nonadopters and adopters in children and adolescents--a consideration of transitional smoking experience: the Bogalusa Heart Study.
A cigarette-smoking questionnaire to examine behavior, attitudes, and beliefs related to cigarette use was administered to children, ages 8-17, in a biracial community. Children who experimented with cigarettes but did not adopt the habit (experimental nonadopters) and children who continued to smoke (adopters) were identified and characterized. Follow-up behavior was examined 2 years later. Adopters were more likely to have smokers as friends and family members, more likely to have purchased their first cigarettes, more likely to believe smoking to be pleasurable for themselves and others, and less likely to consider smoking harmful. Adopters who maintained smoking behavior 2 years later had, during the initial survey, reported having more friends who also smoked and were more likely to believe smoking to be enjoyable. Experimental nonadopters were more likely to try the first cigarette alone, reported having fewer friends and family members who smoked, and believed greater health risks to be associated with cigarette use. Experimental nonadopters who maintained nonsmoking behavior 2 years later, especially in the older cohort, exhibited higher agreement with the negative consequences of cigarette smoking (health beliefs) and theories concerning smoking behavior of others.


Raman Sensitive Degradation and Etching Dynamics of Exfoliated Black Phosphorus.
Layered black phosphorus has drawn much attention due to the existence of a band gap compared to the widely known graphene. However, environmental stability of black phosphorus is still a major issue, which hinders the realization of practical device applications. Here, we spatially Raman map exfoliated black phosphorus using confocal fast-scanning technique at different time intervals. We observe a Raman intensity modulation for , B2g, and modes. This Raman modulation is found to be caused by optical interference, which gives insights into the oxidation mechanism. Finally, we examine the fabrication compatible PMMA coating as a viable passivation layer. Our measurements indicate that PMMA passivated black phosphorus thin film flakes can stay pristine for a period of 19 days when left in a dark environment, allowing sufficient time for further nanofabrication processing. Our results shed light on black phosphorus degradation which can aid future passivation methods.


A comparison of cervical ripening modalities among overweight and obese nulliparous gravidas.
Objective: To determine if differences exist among nulliparous overweight and obese gravidas undergoing cervical ripening employing three different agents (dinoprostone, misoprostol, or cervical catheter).Methods: A retrospective cohort study of nulliparous overweight and obese women who underwent induction of labor at two south-central Pennsylvania hospitals between January 2014 and December 2017. Nulliparous gravidas, ≥37 weeks' gestational age, with singleton pregnancies in the vertex presentation, were included in the study. We employed the following definitions: (1) overweight: BMI 25.0-29.9 kg/m2; (2) class I obesity: BMI 30.0-34.9 kg/m2; (3) class II obesity: BMI 35.0-39.9 kg/m2; and (4) class III obesity: BMI >40.0 kg/m2. The primary outcome measure was the mean difference in induction-to-birth time. A subanalysis was performed to assess the effect of BMI on the primary outcome. Secondary outcome measures included mode of delivery, induction-to-second-stage-of-labor time, estimated blood loss, neonatal feeding type, neonatal Apgar scores, and neonatal admission to triage or intensive care unit (ICU) after delivery. A priori power calculation estimated that 156 patients would be needed using the medium effective size. Data analysis was performed using ANOVA for continuous variables and chi-square tests for categorical variables.Results: Among 192 nulliparous overweight and obese gravidas, 70 received dinoprostone, 72 were given misoprostol, and 50 had cervical ripening with cervical catheters. There were no significant differences in mean induction to birth times among overweight and obese women when comparing the three cervical ripening agents (dinoprostone 24.5 ± 15.2 versus misoprostol 28.7 ± 12.3 and catheters 25.1 ± 12.9 hours), (p = .145, 95% CI -8.7 to 0.2 and -5.5 to 4.3, respectively). Overweight nulliparous women had shorter mean induction to birth time (22.9 ± 11.4 versus 29.2 ± 15.8 hours) as compared to class II obese women, (p = .037, 95% CI -12.0 to -0.38). When overweight women were compared to class III obese women, shorter mean induction to birth time (22.9 ± 11.4 versus 30.9 ± 13.9 hours) was also found, (p = .005, 95% CI -13.4 to -2.4).Conclusion: Among nulliparous overweight and obese gravidas, neither dinoprostone, misoprostol, or cervical catheter significantly impacted the induction to birth time. There was a longer induction to birth time for class II and class III obese women when compared to overweight women. Additional studies are warranted to improve cervical ripening in nulliparous overweight and obese women.


MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.
Multiplex assays of variant effect (MAVEs), such as deep mutational scans and massively parallel reporter assays, test thousands of sequence variants in a single experiment. Despite the importance of MAVE data for basic and clinical research, there is no standard resource for their discovery and distribution. Here, we present MaveDB ( https://www.mavedb.org ), a public repository for large-scale measurements of sequence variant impact, designed for interoperability with applications to interpret these datasets. We also describe the first such application, MaveVis, which retrieves, visualizes, and contextualizes variant effect maps. Together, the database and applications will empower the community to mine these powerful datasets.


Enhancement of motor rehabilitation through the use of information technologies.
The recent development of information technologies has dramatically increased the tools available for facilitating motor rehabilitation. This review focuses on technologies which can be used to augment movement-related information both to patients as well as to their therapists. A brief outline of the motor system emphasizes the role of spinal motor neurons in the control of voluntary movement and rehabilitative efforts. Technologies which induce passive motion to stimulate spinal motor output as well as technologies that stimulate active voluntary movements are discussed. Finally, we review technologies and notational methods that can be used to quantify and assess the quality of movement for evaluating the efficacy of motor rehabilitation efforts. We conclude that stronger evidence is necessary to determine the applicability of the wide range of technologies now available to clinical rehabilitation efforts.