Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis.
The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala. Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the corticotropin-releasing factor (CRF) system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF(1)) antagonist R121919 [2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine)], but not of the CRF(2) antagonist astressin(2)-B, normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the intrinsic properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal.


Emotion Recognition Based on Dynamic Energy Features Using a Bi-LSTM Network.
Among electroencephalogram (EEG) signal emotion recognition methods based on deep learning, most methods have difficulty in using a high-quality model due to the low resolution and the small sample size of EEG images. To solve this problem, this study proposes a deep network model based on dynamic energy features. In this method, first, to reduce the noise superposition caused by feature analysis and extraction, the concept of an energy sequence is proposed. Second, to obtain the feature set reflecting the time persistence and multicomponent complexity of EEG signals, the construction method of the dynamic energy feature set is given. Finally, to make the network model suitable for small datasets, we used fully connected layers and bidirectional long short-term memory (Bi-LSTM) networks. To verify the effectiveness of the proposed method, we used leave one subject out (LOSO) and 10-fold cross validation (CV) strategies to carry out experiments on the SEED and DEAP datasets. The experimental results show that the accuracy of the proposed method can reach 89.42% (SEED) and 77.34% (DEAP).


Nomogram to Predict Intensive Care Following Gastrectomy for Gastric Cancer: A Useful Clinical Tool to Guide the Decision-Making of Intensive Care Unit Admission.
We aimed to generate and validate a nomogram to predict patients most likely to require intensive care unit (ICU) admission following gastric cancer surgery to improve postoperative outcomes and optimize the allocation of medical resources. We retrospectively analyzed 3,468 patients who underwent gastrectomy for gastric cancer from January 2009 to June 2018. Here, 70.0% of the patients were randomly assigned to the training cohort, and 30.0% were assigned to the validation cohort. Least absolute shrinkage and selection operator (LASSO) method was performed to screen out risk factors for ICU-specific care using the training cohort. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction nomogram. The calibration and discrimination of the nomogram were evaluated in the training cohort and validated in the validation cohort. Finally, the clinical usefulness was determined by decision curve analysis (DCA). Age, the American Society of Anesthesiologists (ASA) score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were selected for the model. The concordance index (C-index) of the model was 0.843 in the training cohort and 0.831 in the validation cohort. The calibration curves of the ICU-specific care risk nomogram suggested great agreement in both training and validation cohorts. The DCA showed that the nomogram was clinically useful. Age, ASA score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were identified as risk factors for ICU-specific care after gastric surgery. A clinically friendly model was generated to identify those most likely to require intensive care.


The Number of Ratings Needed for Valid Pain Assessment in Clinical Trials: Replication and Extension.
To provide additional empirical findings regarding the number of pain ratings needed to obtain valid measures for assessing outcomes in pain clinical trials. Secondary analyses of data from a clinical study examining the effects of psychological treatments on pain. Eleven adults with multiple sclerosis and chronic pain reported on four domains of pain intensity (current pain and 24-hour recalled worst, least, and average pain) on four occasions before and after receiving 16 sessions of psychological pain treatments. We evaluated the reliability and validity of four single ratings and 16 different composite scores. Many of the single pain ratings were inadequately reliable while almost all of the composite scores, including the scores created from two ratings, evidenced adequate to excellent reliability. There was a noticeable increase in validity (ability to detect treatment effects) as the number of ratings used increased from one to two. However, there was little change in the validity as the number of items used to create composite scores increased from 2 to 3 or more. The findings also indicated that the scores assessing recalled worst pain were more valid than the scores assessing any of the other pain intensity domains. Composite pain intensity scores created from two individual ratings of recalled pain appear to be adequately valid for detecting treatment effects. Moreover, the findings indicate that the selection of the pain intensity domain to use as a primary outcome variable may play a more important role than increasing reliability by obtaining more assessments; specifically, ratings of recalled worst pain may be more valid for detecting treatment effects than ratings of average pain.


Nonsteroidal management of canine pruritus: chlorpheniramine and a fatty acid supplement (DVM Derm Caps) in combination, and the fatty acid supplement at twice the manufacturer's recommended dosage.
Forty-three dogs having pruritus associated with atopy, flea bite hypersensitivity, and idiopathy were randomly assigned to 1 of 2 treatment protocols. Twenty-three dogs received chlorpheniramine in combination with a fatty acid supplement (DVM Derm Caps). Twenty dogs received the fatty acid supplement at twice the manufacturer's recommended dosage. All 43 dogs were known to be unresponsive to chlorpheniramine and the manufacturer's recommended dosage of the fatty acid supplement when either drug was used alone. Pruritus was satisfactorily controlled in 34.8% of the dogs in the chlorpheniramine--DVM Derm Caps protocol. No dog in the double DVM Derm Caps protocol showed a beneficial response. Side effects were uncommon and mild with either protocol.


Screening of blood donors for human cytomegalovirus (HCMV) IgG antibody with an enzyme immunoassay using recombinant antigens.
Screening of blood donors for human cytomegalovirus (HCMV) infection is usually performed by the combined detection of specific IgG and IgM antibody. However, in most of the cases of primary infection HCMV IgG seroconversion is observed concomitantly to IgM production and HCMV IgM antibody detection for blood donor screening is subject to a relatively high frequency of false positive results. In the present study a newly established HCMV IgG ELISA based on recombinant antigens (anti-HCMV recombinant IgG ELISA, Biotest) was evaluated in terms of sensitivity and specificity for blood donor screening. A total of 442 serum samples including follow-up sera of five patients suffering from primary HCMV infection, selected seropositive and seronegative blood donors and routine specimens were comparatively investigated with three HCMV antibody ELISAs (anti-HCMV recombinant IgG ELISA, Biotest; Enzygnost anti-CMV/IgG + IgM, Dade Behring; and Captia CMV-TA, Centocor). IgG seroconversion was detected with anti-HCMV recombinant IgG ELISA as early as IgM in all five patients suffering from primary infection. The alternative ELISAs were less sensitive, detecting seroconversion one to three bleeds later in 2 (Enzygnost anti-CMV/IgG + IgM) and 4 patients (Captia CMV-TA), respectively. Anti-HCMV recombinant IgG ELISA showed a 99.1% agreement with Enzygnost anti-CMV/IgG + IgM and/or Western blot in the preselected blood donors and routine specimens. Relatively high numbers of false negative (n=20) and positive results (n=7) were obtained with Captia CMV-TA. Our preliminary data suggest that HCMV antibody screening of blood donors can be performed reliably by detection of specific IgG provided that a highly sensitive assay system is used.


The phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 affects phot2-dependent phototropism in Arabidopsis.
The blue light photoreceptors, phototropin 1 (phot1) and phot2, and their signal transducer, NONPHOTOTROPIC HYPOCOTYL3 (NPH3), are activators of the phototropic responses of Arabidopsis hypocotyls. In a recent study, we reported that the control of NPH3 phosphorylation at serine 7 (S7: or S5), S213, S223, S237, S467, S474 (or S476), and S722 (or S723) contributes to the photosensory adaptation of phot1 signaling during the phototropic response. Phosphomimetic NPH3SE mutant and unphosphorylatable NPH3SA mutant on those serine residues function efficiently under blue light conditions at fluence rates of 10-5 µmol m-2 s-1 and 10-3 µmol m-2 s-1 or more, respectively. We here demonstrate that phosphomimetic NPH3SE, but not unphosphorylatable NPH3SA, promotes phot2-dependent phototropism under blue light condition at 100 µmol m-2 s-1. This result suggests that phot1 negatively controls phot2 signaling through the dephosphorylation of NPH3 at those residues and that the hyperactivation of phot1- and phot2-NPH3 complexes does not occur at the same time under high intensity blue light. We hypothesize that the dephosphorylation of NPH3 on those serine residues suppresses both phot1 and phot2 signaling, which results in different impacts on phot1- and phot2-dependent hypocotyl phototropism due to the differences in the photosensitivity and activation levels of phot1 and phot2.


Heterogeneous allele expression of pulmonary SP-D gene in rat large intestine and other tissues.
Random allele expression has recently been observed for several genes including interleukins and genes of the lymphoid system. We studied the hypothesis that the surfactant protein D (SP-D) gene, an innate host defense molecule, exhibits random allele expression in a tissue-specific manner. SP-D gene expression is tissue specific in the 14 tissues studied. Study of SP-D allelic expression in several tissues revealed a balanced biallelic (BB) in lung, and, in several extrapulmonary tissues, a heterogeneous pattern: BB, imbalanced biallelic (IB), and monoallelic (MO). The results from 103 heterozygous rats showed an expression profile in large intestine of BB (22%), IB (58%), and MO (20%). Among eight families, the percent of BB in siblings varied from 0 to 41%, MO from 0 to 33%, and IB from 49 to 83%. The parent-of-origin does not play a role in SP-D allele-specific expression. However, acquired epigenetic factors, family background, or other factors may contribute to the overall pattern of expression.


Allergy: a leading role in otitis media with effusion.
We have studied 35 children with seasonal allergic rhinitis confirmed by positive skin tests and RAST to grass pollen. Intranasal antigen provocation was performed to evaluate the function of the eustachian tube (ET) and middle ear pressure (MEP). Tympanometry was used to evaluate the changes in MEP, while Valsava and Toynbee tympanometric tests were employed to study the ET function, and the changes in nasal airway resistance were measured by anterior rhinomanometry. ET dysfunction (ETD) and a decrease in MEP and nasal airway resistance were demonstrated in the children under study as compared with the controls. The results suggest a role for allergy in ETD and for the development of OME.


Effect of microwave ablation on platelet and coagulation function in patients with BCLC-A hepatocellular carcinoma.
To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma (B-A-HCC) using a retrospective method. A total of 36 patients with 48 B-A-HCCs were radically treated with MWA alone under the guidance of ultrasound between April and October 2018. PLT coagulation indexes were measured before and after MWA at 1 day, 3 days, 1 week, and 2 weeks, and blood samples (after morning fasting) were collected from cubital veins. Coagulation indexes included prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), Activated Partial Thromboplastin Time (APTT), international standardized ratio (INR), plasma fibrinogen (FIB), plasma antithrombin III (AT-III), and D dimer (DD). Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), and adverse reactions were also recorded. All patients were radically treated with MWA alone. The median size of the lesion was 2.6 (1.5-7.0) cm3. On the first day after MWA, the level of PLT decreased significantly compared with the values before MWA and gradually returned to preoperative levels one week after MWA. One day after MWA, the levels of PT, INR, and AT-III increased markedly and the level of PTA decreased significantly, all of them gradually returned to baseline after 3 days to a week of time. 1, 3, and 7 days after MWA, the levels of FIB, and DD increased significantly, and the level of TT decreased significantly; all of them gradually returned to baseline at 2 weeks. At 6 months posttreatment, the OS and RFS rates were 100% and 91.7%, the LTP rates was 5.6%, no significant adverse reactions. PLT and coagulation indexes were abnormal in patients with B-A-HCC who were radically treated with MWA alone after treatment; without specific treatment, they all gradually returned to baseline within a week or two.


Major dietary patterns and predicted cardiovascular disease risk in an Iranian adult population.
Limited data are available on the association of major dietary patterns and predicted risk of cardiovascular disease (CVD) using the Framingham Risk Score (FRS). To investigate the association between major dietary patterns and the predicted 10-year CVD risk in an Iranian population. This cross-sectional study was conducted on 522 apparently healthy adults referred to health centers in Tehran. Usual dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary patterns and the predicted risk of development of CVD was evaluated using linear multiple regression. Principal component analysis was used to identify major dietary patterns. In total, 41% of the men (n = 95) and 46% of women (n = 134) were in the low risk (<10%) and 6% of men (n = 14) and 1% of women (n = 3) were in the high risk (> 20%) category of the FRS. A significant decrease was found for body mass index (p < 0.001), systolic blood pressure (SBP) (p = 0.003), diastolic blood pressure (p = 0.005), and triglyceride (p = 0.02) in the higher tertile of healthy dietary pattern. Adherence to an unhealthy dietary pattern was associated with a significant increase in body weight (p = 0.03) and a significant decrease in high-density lipoprotein cholesterol (p < 0.001). The healthy dietary pattern score was negatively associated with SBP (p = 0.04) and FRS (p < 0.001). Although we observed improvements in CVD risk factors with greater adherence to healthy dietary patterns, there was no association between identified dietary patterns and the predicted risk of 10-year CVD.


Apical leakage of resin based root canal sealers with a new computerized fluid filtration meter.
In this in vitro study, the apical leakage of three root-canal sealers: AH Plus, Diaket, and EndoREZ was evaluated using a new computerized fluid filtration meter. Forty-five extracted human premolar teeth with single root and canal were used. The coronal part of each tooth was removed and the root canals were prepared using GT Rotary files and crown-down technique. The roots were randomly divided into three groups of 15 samples, filled with one of the test materials and gutta-percha cones by the cold lateral condensation technique and were stored at 37 degrees C and 100% humidity for 7 days. One-week later, apical parts of roots of 10 +/- 0.05 mm were attached to computerized fluid filtration meter. Apical leakage quantity was determined as microl/cmH(2)O/min(-1). Statistical analysis indicated that root fillings with Diaket in combination with cold lateral condensation technique showed lower apical leakage than the others (p < 0.05). In addition, this new computerized fluid filtration meter allowed quantitative measurement of leakage easily. As it is a newly developed device to measure apical leakage of endodontic sealers, the reliability of it needed to be tested.


[Examination of the stability of hydrogen peroxide solutions].
Reliable stabilization of the pharmaceutical preparation and the active ingredient remains one of the most important problems of world pharmacy because pharmaceutical preparations are not systems which are stable without limitation. The patient must receive a quality drug and that is why the question of stability is paid grest attention to not only in research and development, industrial manufacture, but also in distribution. The measure of stability is the expiration period. Diluted solution of hydrogen peroxide (3% solution) still belongs to the most widely used and at the same time the most easily accessible disinfectants. In practice it is common both in Slovakia and abroad. It is used in several concentrations. One of its most important disadvantages is its limited stability, which markedly decreases its expiration period. The present paper investigates the stability of hydrogen peroxide solutions of routinely used concentrations (3%, 6%, and 10%) without and with a stabilizing additive (phenacetin) prepared in the pharmacy and stored under different conditions for the period of their expected usability. The content of hydrogen peroxide was assayed by the pharmacopoeial method in 7-day time intervals. All concentrations of 3%, 6%, and 10% hydrogen peroxide were found to fulfil the conditions for stability in the period of time under study. Their concentration did not fall below the limit od 90% of the content of the active ingredient, and storage under decreased temperature proved to be more suitable. Storage of hydrogen peroxide in the light is inadmissible. When the conditions of storage are observed, the required therapeutic effect of hydrogen peroxide solution can be expected for the period of three months.


First isolation of Arcanobacterium pinnipediorum from a grey seal pup (Halichoerus grypus) in the UK.
In the present study, a single Arcanobacterium (A.) pinnipediorum strain isolated from discharge of a jaw swelling of a grey seal pup (Halichoerus grypus) in England, UK, was identified. This strain was further characterized by phenotypical investigations, by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), by Fourier transform infrared spectroscopy (FT-IR), and genotypically by sequencing the 16S rRNA gene and the genes gap encoding glyceraldehyde 3-phosphate dehydrogenase, tuf encoding elongation factor tu, and rpoB encoding the β subunit of bacterial RNA polymerase. The present study gives a first detailed characterization of the species A. pinnipediorum from a grey seal in the UK. However, the route of infection of the grey seal with the bacterial pathogen remains unclear.


Distraction of task-relevant information processing by irrelevant changes in auditory, visual, and bimodal stimulus features: a behavioral and event-related potential study.
Distractibility with auditory, visual, and bimodal stimulus changes was investigated using an audio-visual distraction paradigm. Participants were asked to discriminate between equiprobable short and long audio-visual stimuli. Infrequently, the auditory, the visual, or both parts of the stimuli changed. These rare deviations (deviants) were irrelevant for the actual task. The influence of the three types of deviant stimuli on the processing of task-relevant information was assessed with behavioral and event-related potential (ERP) measures assuming that bimodal deviants would lead to an increase in distraction. Behavioral and ERP results did not support this assumption, as reaction time (RT) prolongation and components amplitudes did not differ significantly for auditory and bimodal deviants. It is suggested that a maximal threshold of distraction accounts for these results. In addition, the processing of bimodal deviations was assessed. Audio-visual interactions were found following modality-specific deviance detection suggesting that integration only occurs with involuntary attention switching to task-irrelevant changes.


[Effect of magnesium on postischemic reperfused myocardial mitochondria].
Isovolumic rat heart preparations were exposed to low flow ischemia (0.2 ml/min) for 60 min, followed by 30 min of reperfusion. The concentration of Mg2+ was maintained 1.2 mmol/L throughout the study in group 2, while increased to 15 mmol/L or depleted to zero during ischemia only in group 3 and group 1 respectively. High concentration Mg2+ showed a significantly protective effect on Ca-ATPase activity and synthesis ability of ATP in myocardial mitochondria, and decreased its calcium overload. Thus it appears that high concentration Mg2+ infusion may partially reverse postischemic reperfusion injury to heart.


Assessing the performance of 3D pharmacophore models in virtual screening: how good are they?
Pharmacophore approaches have evolved to be one of the most successful tools in drug discovery, especially since the past two decades. 3D pharmacophore methods are now commonly used as part of more complex workflows in drug discovery campaigns, and have been successfully and extensively applied in virtual screening (VS) approaches. This review provides a perspective of how to assess the performance of 3D pharmacophore models to be used in VS. Since 3D VS protocols are in general assessed by their ability to discriminate between active and inactive compounds, we summarize the impact of the composition and preparation of modeling and external sets on the outcome of evaluations. Moreover, we highlight the significance of both classic enrichment parameters and advanced descriptors for the performance of 3D pharmacophore-based virtual screening methods.


Lack of norepinephrine--neuropeptide Y interactions in the hypothalamic control of cardiovascular regulation in urethane-anesthetized rats.
Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 microL were at 1.0 microL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependent increases in blood pressure with latencies of approximately 1 min, which peaked by 3-5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of metabolic syndrome on re-stenosis development: role of drug-eluting stents.
Metabolic syndrome (MetS) is defined as a cluster of numerous cardiovascular risk factors, which encompasses obesity, dyslipidaemia, insulin resistance and hypertension. Patients with MetS are more prone to developing cardiovascular events than other patients. To date, several approaches such as physical exercise, dietary control and invasive and non-invasive therapeutic interventions for dyslipidaemia, hypertension and insulin resistance have been used to manage MetS. However, there is a progressive elevation in the incidence of fatal and non-fatal cardiovascular events due to the increased prevalence of obesity and diabetes. Percutaneous coronary intervention has emerged over the last few years as an effective revascularisation strategy for those with coronary artery disease, in parallel with the development of effective anti-platelet medications and newer drug-eluting stents. In recent years, considerable research efforts have been undertaken to elucidate the pathophysiology of re-stenosis and develop strategies to prevent re-stenosis following percutaneous transluminal coronary angioplasty and stent implantation. Although the rate of stent re-stenosis and target-lesion revascularisation has been reduced, there is little information in the literature on the outcome of MetS in the pathophysiology of re-stenosis. In this review article, we summarise the recent development and progress on re-stenosis and the role of drug-eluting stents, particularly in MetS.


Tyrosinaemia type II with diffuse plantar keratoderma and self-mutilation.
Tyrosinaemia type II (oculocutaneous tyrosinaemia or Richner-Hanhart syndrome) is a rare and potentially treatable genetic disorder. Corneal opacities or ulcers, circumscribed palmoplantar keratoderma and subnormal intelligence form the classical triad of this syndrome. A case with additional features of self-harm and diffuse plantar keratoderma is discussed. Emphasis is laid on the importance of early diagnosis and intervention in the form of dietary regulation to prevent the neurological signs and treat the oculocutaneous symptoms.


Temperature and duration of heating of sunflower oil affect ruminal biohydrogenation of linoleic acid in vitro.
Sunflower oil heated at 110 or 150 degrees C for 1, 3, or 6h was incubated with ruminal content in order to investigate the effects of temperature and duration of heating of oil on the ruminal biohydrogenation of linoleic acid in vitro. When increased, these 2 parameters acted together to decrease the disappearance of linoleic acid in the media by inhibiting the isomerization of linoleic acid, which led to a decrease in conjugated linoleic acids and trans-C18:1 production. Nevertheless, trans-10 isomer production increased with heating temperature, suggesting an activation of Delta(9)-isomerization, whereas trans-11 isomer production decreased, traducing an inhibition of Delta(12)-isomerization. The amount of peroxides generated during heating was correlated with the proportions of biohydrogenation intermediates so that they might explain, at least in part, the observed effects. The effects of heating temperature and duration on ruminal bacteria community was assessed using capillary electrophoresis single-strand conformation polymorphism. Ruminal bacterial population significantly differed according to heating temperature, but was not affected by heating duration. Heating of fat affected ruminal biohydrogenation, at least in part because of oxidative products generated during heating, by altering enzymatic reactions and bacterial population.


Ischemia-modified albumin use as a prognostic factor in coronary bypass surgery.
Various types of markers have been used so far in order to reveal myocardial perfusion defect. However, these markers usually appear in the necrosis phase or in the late stage. Having been the focus of various investigations recently, ischemia-modified albumin (IMA) is helpful in establishing diagnosis in the early stages of ischemia, before necrosis develops. 30 patients that underwent only coronary bypass surgery due to ischemic heart disease within a specific period of time have been included in the study. IMA levels were studied in the preoperative, intraoperative, and postoperative periods. The albumin cobalt binding assay was used for IMA determination. Hemodynamic parameters (atrial fibrillation, the need for inotropic support, ventricular arrhythmia) of the patients in the postoperative stage were evaluated. Intraoperative measurement values (mean ± SD) of IMA (0.67677 ± 0.09985) were statistically significantly higher than those in the preoperative (0.81516 ± 0.08894) and postoperative (0.70477 ± 0.07523) measurements. Considering atrial fibrillation and need for inotropics, a parallelism was detected with the levels of IMA. IMA is an early-rising marker of cardiac ischemia and enables providing a direction for the treatment at early phases.


Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase.
AMP-activated protein kinase (AMPK) is a critical energy-balancing sensor in the regulation of cellular metabolism in response to external stimuli. Emerging evidence has suggested that AMPK is a potential therapeutic target for human cancers. AICAR, one of the pharmacological AMPK activators, has been widely used to suppress cancer cell growth through activation of LKB1, an upstream kinase of AMPK. However, frequent mutations and deletions of LKB1 found in some cancer cells limit the application of AICAR as an efficient therapeutic drug. Here we show that an alternative pharmacological AMPK activator, A23187, was able to inhibit cervical cancer cell growth through activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta, another upstream kinase of AMPK. Using cervical cancer cell models, we found that HeLa (LKB1-deficient cell) responded less to the anti-proliferative effect exerted by AICAR treatment (p < 0.001) compared with CaSki and C41 (LKB1-expressing cells). Conversely, the anti-proliferative effect was increased significantly in HeLa but not in CaSki and C41 cells under treatment by A23187 (p < 0.001). Moreover, co-treatment of AICAR and A23187 was able to further enhance the inhibitory effect on cell growth of Hela, CaSki and C41 cells. Notably, both AICAR and A23187 exerted the anti-proliferative effect on cervical cancer cells by suppressing AMPK/mTOR signalling activity. These data suggest that A23187 could be an alternative potential therapeutic drug used for anti-proliferation in LKB1-deficient cancer cells.


Outreach obstetrics training in Western Australia improves neonatal outcome and decreases caesarean sections.
The objective of this study was to determine the effect of a multi-professional outreach obstetric training programme on perinatal and neonatal outcomes. This was a retrospective comparison of 5-min low Apgar scores, stillbirth, perinatal death and moderate/severe hypoxic ischaemic encephalopathy rates in 127,753 infants born in Western Australia before and after the introduction of training in rural and remote areas. Following the introduction of the training programme, there was a highly significant (p = 0.003) decrease in the rate of infants born with low 5-min Apgar scores (from 20.4 to 15.4/1,000 live births). While the changes in the other three outcomes were not significant, all three demonstrated a trend for improvement in the intervention area. This is the second study of an educational intervention in obstetrics to demonstrate improvement in neonatal outcome and the first to be associated with a decrease in caesarean sections.


Two-dimensional photonic crystals with large complete photonic band gaps in both TE and TM polarizations.
Photonic crystals exhibiting a photonic band gap in both TE and TM polarizations are particularly interesting for a better control of light confinement. The simultaneous achievement of large band gaps in both polarizations requires to reduce the symmetry properties of the photonic crystal lattice. In this letter, we propose two different designs of two-dimensional photonic crystals patterned in high refractive index thin silicon slabs. These slabs are known to limit the opening of photonic band gaps for both polarizations. The proposed designs exhibit large complete photonic band gaps: the first photonic crystal structure is based on the honey-comb lattice with two different hole radii and the second structure is based on a "tri-ellipse" pattern in a triangular lattice. Photonic band gap calculations show that these structures offer large complete photonic band gaps deltaomega/omega larger than 10% between first and second photonic bands. This figure of merit is obtained with single-mode slab waveguides and is not restricted to modes below light cone.


The study of the relationship between lifestyle characteristic self-reported drinking patterns and trauma.
A total of 161 usable interviews were obtained with 297 consecutive admissions to a Level I trauma center for purposes of evaluating patient socioeconomic patterns related to trauma. The median age of the purposeful sample was 31. There were 67.1% males, 29.2% females, and 3.7% unidentified; 43.5% were MVAs, 8.1% motorcycles, 2.5% pedestrians, 10.6% falls, and 3.7% penetrating trauma. Of those patients found ETOH positive, 40.8% admitted to drinking and driving regularly, 12.5% admitted to being previously arrested for DUI, 45% admitted that alcohol caused their current trauma, 28.6% had been previously arrested for traffic violation. Three-fourths did not routinely wear seat belts. The average education level of trauma victims was 12.2 years; 94% are blue collar workers. In summary the average trauma victim was a young adult male who had completed high school, somewhat below average earnings, and had a strong history of regular alcohol use as part of his lifestyle.


The histopathological feature of the nail isthmus in an ectopic nail.
The nail unit has a unique structure. It has been recently proposed that the nail isthmus as a transitional zone between the most distal part of the nail bed and the hyponychium. A 7-year-old Japanese boy presented with an ectopic nail, an additional and independent miniature nail on the digital pulp of the right fifth finger. We studied the expression of a series of keratin in longitudinal specimens and showed the histopathological manifestation in the nail isthmus. This region in the ectopic nail is subdivided into 2 parts: a proximal and narrow part anchored to the nail plate and a distal and wide part with a semihard keratinized structure.


Plasma elimination kinetics for factor VII are independent of its activation to factor VIIa and complex formation with plasma inhibitors.
The mechanism for the elimination of factor VII (FVII) from the circulation is unknown, just as it is unclear how activation of FVII to FVIIa and subsequent complex formation with antithrombin III (AT) or alpha2-macroglobulin (alpha2M) affects clearance. The possibility that the clearance mechanism involves activation and inhibitor complex formation as obligatory intermediate reactions is examined in this study. Human and murine sera were spiked with human FVIIa in the absence and presence of heparin and analysed for complex formation. Complex formation in vivo was studied after intravenous injection of (125)I-VIIa in mice; and the pharmacokinetics (PK) of human and murine FVIIa was studied in normal mice. Furthermore, comparative PK studies were performed with FVII, FVIIa, active site blocked FVIIa and a preformed FVIIa-AT complex in normal and alpha2M-deficient mice. The data demonstrated that FVIIa-AT complexes and to a much lesser extent FVIIa-alpha2M-complexes accumulated in vivo after FVIIa administration. FVIIa-AT accounted for about 50% of total FVIIa antigen left in the circulation after 3 hours. All FVII derivatives studied including FVII, FVIIa and FVIIa-AT were cleared with similar rates suggesting an elimination kinetics which is unaffected by FVII activation and subsequent inactivation by plasma inhibitors.


Cutaneous manifestations of aortoiliac occlusive disease: two cases and review of the literature.
Aortoiliac occlusive disease (AIOD) is non-inflammatory obstructive vasculopathy commonly affecting patients with advanced atherosclerosis, diabetes mellitus, or elevated cholesterol levels, and subjects with other risk factors such as cigarette smoking.Two Caucasian patients (a 55-year-old woman and a 56-year-old man), with ulcerous cutaneous lesions of AIOD are reported. In both cases, medical history comprises initial lower limb claudication, multiple painful ulcers along the legs and absence of superficial femoral artery pulse. Severe obstruction of both infrarenal aorta and iliac arteries on the left side was demonstrated by contrast angiography and Doppler ultrasonography.The evolution of the disease showed some characteristic findings, including pyoderma gangrenosum-like ulcerations as the initial cutaneous manifestation of AIOD, multiple painful ulcers along the lower extremities, and aorto-iliac occlusive disease due to atherosclerosis.Early diagnosis and surgical reconstruction of vessels in patients with AIOD improved quality of life and limb salvage rates.


Using post-breakdown conduction study in a MIS structure to better understand the resistive switching mechanism in an MIM stack.
We apply our understanding of the physics of failure in the post-breakdown regime of high-κ dielectric-based conventional logic transistors having a metal-insulator-semiconductor (MIS) structure to interpret the mechanism of resistive switching in resistive random-access memory (RRAM) technology metal-insulator-metal (MIM) stacks. Oxygen vacancies, gate metal migration and metal filament formation in the gate dielectric which constitute the chemistry of breakdown in the post-breakdown stage of logic gate stacks are attributed to be the mechanisms responsible for the SET process in RRAM technology. In this paper, we draw an analogy between the breakdown study in logic devices and filamentation physics in resistive non-volatile memory.


Synergism of IL-2-stimulated splenocytes and Pentostam enhances the killing of Leishmania donovani in vitro.
Control of infections by the obligate intramacrophage protozoan parasite Leishmania donovani is traditionally done with pentavalent antimonial drugs. It was of interest to determine if immunotherapy with IL-2-stimulated splenocytes would enhance drug action in an in vitro model system. It is confirmed that nontoxic doses of Pentostam decrease infection in a dose-dependent manner in vitro in terms of both the number of amastigotes/100 macrophages and the % of infected macrophages; the curative effect was most apparent when the drug was used on the 7th day of the infection, when the parasite was in its proliferative phase. It is also confirmed that recombinant IL-2-stimulated splenocytes induced infected macrophages to reduce significantly their parasite burden, especially when the infection was treated in the nonproliferative phase of the parasite, also in a dose-dependent manner. Leishmanicidal action in the infected macrophages was induced by cytokine(s) released from the lymphokine-stimulated cells. Immunotherapy in the nonproliferative phase, combined with drug treatment in the proliferative phase, reduced the infection to levels significantly below those produced by either treatment alone. Immunotherapy with IL-2-stimulated splenocytes in combination with Pentostam is, therefore, an excellent candidate treatment for the effective reduction of experimental infections by L. donovani.


DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma.
Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals. Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P < 0.001). Higher levels of 5hmC were found in lower grades of the International Staging System prognostic index (P < 0.05) and tend to associate with a longer overall survival (P < 0.1). From the hydroxymethylome data, we observed that the remaining 5hmC is organized in large domains overlapping with active chromatin marks and chromatin opening. We discovered that 5hmC strongly persists at key oncogenic genes such as CCND1, CCND2 and MMSET and characterized domains that are specifically hydroxymethylated in myeloma subgroups. Novel 5hmC-enriched domains were found at putative enhancers of CCND2 and MYC in newly diagnosed patients. 5hmC level is associated with clinical aspects of MM. Mapping 5hmC at a genome-wide level provides insights into the disease biology directly from genomic DNA, which makes it a potent mark to study epigenetics on large patient cohorts.


Doctors' Choice of Medical Specialty, Differences Among Schema Theory.
In previous studies, the relationship between career choice and psychological factors has been discussed many times. On the other hand, we have less information about interaction between early maladaptive schemas and career choice. We planned to evaluate the specialty preferences of doctors in the perspective of schema theory. Doctors from the 2 to 10 years of their careers were included in the study. A Sociodemographic data form and Young Schema Questionnaire - Short Form 3 was applied to 275 participants; 167 clinical specialties and 108 surgical specialties. According to our results surgeons scored higher in emotional deprivation, mistrust / abuse, social isolation / alienation, defectiveness / shame, and emotional inhibition. As schema domains, surgeons scored higher disconnection and rejection and excessive responsibility and standards. Early maladaptive schemas can affect the choice of profession and the ability to adapt. Understanding early maladaptive schemas can play a role both in orientation towards the right career choice and in resolving negative factors related to the work environment.


[Perforation of a stomach ulcer into the left heart ventricle. Case report and review of the literature].
We present a case of peptic-ulcer perforation from the stomach into the left ventricle. The patient who had no prior cardiac or abdominal symptoms was admitted with gastrointestinal bleeding and the electrocardiographic signs of myocardial infarction of the posterior wall. After the bleeding had subsided for 5 hours the patient died suddenly from massive upper gastrointestinal bleeding. At autopsy a peptic ulcer was found 3 cm beneath the cardia in the anterior wall on the lesser curvature which had perforated dorsal from the papillar muscle into the left ventricle. In the literature 19 such ulcer perforations have been reported which are compared with the present case.


Effect of tube feedings on the measurement of gastric intramucosal pH.
To determine the effect of enteral tube feedings on the measurement of gastric intramucosal pH. Interventional study. Two intensive care units of a university-affiliated teaching hospital. Twenty hemodynamically stable patients undergoing mechanical ventilation, with a nasogastric tonometer in situ, in whom enteral feeding was initiated. The baseline fasting gastric intramucosal pH and gastric fluid pH were determined in the study population. The patients then received enteral feedings for 2 hrs, after which the gastric intramucosal pH and gastric fluid pH measurements were repeated. The tube feedings were then withheld for 2 hrs. The data set was repeated 1 and 2 hrs after the feedings had been stopped. Finally, tube feedings were retarded and the data set was repeated after 4 hrs. All patients received a histamine-2 (H2)-receptor antagonist-blocking agent during the study. To investigate the possibility that a direct reaction between gastric fluid and enteral feedings may generate CO2, 30-mL aliquots of gastric fluid from an independent sample of 14 patients (seven receiving cimetidine) were mixed with 60 mL of enteral feeding in an airtight container; the PCO2 of the gastric fluid before and after adding enteral feeding was measured tonometrically. The mean +/- SD gastric intramucosal pH decreased from 7.40 +/- 0.08 to 7.33 +/- 0.12 (p < .005), and from 7.38 +/- 0.07 to 7.31 +/- 0.1 (p < .005) after the first and second feeding challenges, respectively. The gastric intramucosal pH returned to the baseline value after 1 hr of fasting. The mean in vitro PCO2 of the gastric fluid increased from 11.9 +/- 3.0 to 16.2 +/- 2.0 torr (1.6 +/- 0.4 to 2.1 +/- 0.27 kPa) (p = .003) after the addition of tube feedings in the samples from those patients who were not receiving H2 receptor antagonists, but did not change significantly in those samples from the patients who were receiving H2 receptor antagonists. Enteral feeding stimulates the secretion of hydrogen ions, which are then buffered by ionized bicarbonate secreted by the nonparietal gastric cells generating CO2. In addition, the enzymatic digestion of nutrients in the stomach may also generate CO2. The increased intraluminal CO2 following enteral feeding results in a spuriously low gastric intramucosal pH reading. Our data suggest that tube feedings should be temporarily discontinued for at least 1 hr when measuring the gastric intramucosal pH. These data should, however, be used with caution when extrapolating to hemodynamically unstable patients. Furthermore, the consequences of frequent interruptions of enteral feeding need to be weighed against the possible benefits derived from the use of this monitoring tool.


Nursing research conventions: objectivity or obfuscation?
This paper is a critique of naïve realism, the philosophy which animates much nursing research, and which leads researchers to assume that the attainment of objective knowledge is possible. The nature of naïve realism, and its relationship to objectivity, is discussed. Central to this outlook is the belief that the values and interests of the researcher can and should be divorced from the prosecution of research. This is reflected in the literary convention of referring to the researcher in the third person. Contrary to this position, I argue that the interpretations, values and interests of the researcher are central to the research process. Moreover, nursing research may be affected by the interests of managers, educationalists, and those who wish to see nursing attain professional status. Nursing researchers should accept that they are part of the social situations which they study. They should therefore become reflexive in their outlook. This entails recognizing and attempting to understand the effects of the researcher, rather than trying to eliminate or ignore them.


[Safety and efficacy of classic ambulatory implantable cardioverter-defibrillator and resynchronisation systems follow-up compared to telemetric follow-up].
Telemetric follow-up (RM) after cardiac devices implantation is not only not inferior to classic follow-up, but also enables earlier clinical complications detection and stricter patient monitoring. of the study was to confirm safety and efficacy of RM in patients with implantable cardioverter-defibrillator (ICD) or cardioverterdefibrillator with resynchronisation therapy (CRT-D), compared to traditional follow-up in outpatient clinic. Group A (CRT-D+ICD) (retrospective, patients followed-up in outpatient clinic) was consisted with 273 patients (mean age 65±11 years, 230M). Group A included 128 patients after CRT-D implantation and 145 patients with ICD. Group B (RM group) (prospective, RM Medtronic CareLink follow-up) involved 89 patients (mean age 61±14 years, 73M). 11 patients had CRT-D and 78 had ICD implanted. Only patients with Medtronic equipment were included to group B. Follow-up of patients from group A - ambulatory visit in outpatient clinic: 1-3 months after implantation, then every 6 months. Follow-up of patients from group B - daily follow-up using RM system (Medtronic CareLink). Patient's clinical status, medications, frequency/ type of arrhythmias, device interventions were assessed in both groups. To assess presence of ventricular arrhythmia, device interventions, ICD and CRT-D programming changes, pharmacotherapy changes, a number of patients were randomly chosen from group A. They were similar in age, gender, LVEF value, NYHA class, comorbidities, time of follow-up (control group) to Group B (RM group). In the RM group, compared to control group, there were significantly less programming changes (3,4 vs 28,6%, p<0,001), time to first event was shorter (ventricular arrhythmia - 39 days, p<0,001; intervention - 102 days, p<0,001), time to first necessary programming change was longer (201 days, p<0,001). RM system proved to be save, more accurate (22% visits were performed personally by the physician operating Medtronic CareLink system, 71,4% consultations were performed via internet, phone), and general mortality did not differ significantly between the groups (p=0,147). Telemetric follow-up of cardiac implantable devices is a safe and more accurate method in comparison to classic ambulatory follow-up. Telemetric follow-up of cardiac implantable devices enables quick information transmission in case of clinical complications (arrhythmia, intervention). Telemetric follow-up allows to reduce number of ambulatory visits to only necessary ones.


[The migratory movements of young people who left English-language high schools in Quebec in 1971].
"The present article is an abridged version of the last of four reports on a longitudinal study of migratory movements, in and out of Quebec, of one cohort of young anglophones, those who left high school in Quebec in 1971." The data concern 975 individuals, who are a representative sample of those leaving English-language high schools in Quebec in 1971. The subjects were followed up in 1979 and again in 1982-1983. The results indicate that by 1982-1983, about 50 percent of those surveyed had left the province. (summary in ENG, SPA)


[Clinical and anatomical features of SARS-COV-2 with acute hemorrhagic necrotizing encephalopathy].
Autopsy material and medical history were studied and analyzed in a 20-year-old male patient who had died from COVID-19 infection with the development of acute SARS-CoV-2-associated hemorrhagic necrotizing encephalopathy in adults with obvious endothelial dysfunction confirmed by virological examination of the autopsy material. In this case, the brain structures displayed the main found histopathologic signs: widespread vasculitis (endotheliitis) with varying degrees of segmental and total endothelial destruction; thrombosis mainly of the vessels of the microcirculatory bed; parenchymal hemorrhagic necrosis and inflammation (encephalitis); severe necrobiotic damage to neurons. Cerebrovascular immune damages and hypercoagulable states, which were observed in some acute viral neuroinfections, are the basis for the neurological complications of COVID-19. In this case of bicausal diagnosis (the presence of a comorbidity), the primary disease contributed to the acute progression of the background disease (secondary infiltrative tuberculosis with the development of specific pleuritis and pneumothorax with the addition of acute bilateral focal confluent bronchopneumonia with a history of undifferentiated immunodeficiency syndrome. Emphasis is laid on the possibility and importance of involving the brain structures in the process in COVID-19 for the timely diagnosis of emerging neurological disorders. A brief literature review is given.


The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis.
The farnesoid X receptor (FXR) is an endogenous sensor for bile acids and inhibits bile acid synthesis by inducing small heterodimer partner (SHP) gene expression. The aim of this study was to investigate whether FXR is expressed by and modulates function of hepatic stellate cells (HSCs). The antifibrotic activity of FXR ligand was tested in 2 rodent models: the porcine serum and bile duct ligation (BDL). Twelve-week administration of 1-10 mg/kg 6-ethyl chenodeoxycholic acid (6-ECDCA), a synthetic FXR ligand, to porcine serum-treated rats prevented liver fibrosis development and reduced liver expression of alpha1(I) collagen, TGF-beta1 and alpha-SMA mRNA by approximately 90%. Therapeutic administration of 6-ECDCA, 3 mg/kg, to BDL rats reduced liver fibrosis and alpha1(I) collagen, transforming growth factor (TGF)-beta1, alpha-SMA, and tissue metalloproteinase inhibitor (TIMP)-1 and 2 messenger RNA (mRNA) by 70%-80%. No protection was observed in BDL rats treated with CDCA, 3 mg/kg, and ursodeoxycholic acid, 15 mg/kg. FXR expression was detected in HSCs. Exposure of HSCs to FXR ligands caused a 3-fold increase of SHP, reduced alpha1(I)collagen and TGF-beta1 by approximately 60%-70% and abrogates alpha1(I) collagen mRNA up-regulation induced by thrombin and TGF-beta1. By retrovirus infection and small interference RNA, we generated SHP overexpressing and SHP-deficient HSC-T6. Using these cell lines, we demonstrated that SHP binds JunD and inhibits DNA binding of adaptor protein (AP)-1 induced by thrombin. By demonstrating that an FXR-SHP regulatory cascade promotes resolution of liver fibrosis, this study establish that FXR ligands might represent a novel therapeutic option to treat liver fibrosis.


Study of Peripheral Mononuclear Cells and CD34 Levels as a Predictive Marker for Initiating Apheresis in Autologous Stem Cell Transplant.
Background: Autologous HCT in multiple myeloma is done as upfront treatment in newly diagnosed transplant eligible patients after induction chemotherapy. In addition, it is standard for relapsed, aggressive non-Hodgkin lymphoma (NHL) and classical Hodgkin lymphoma (HL), and is curative in ~40% to 45% of patients. Over a decade, many efforts were made to find helpful parameters to predict an optimal time for initiating an efficient peripheral blood stem cell collection so that adequate stem cells are collected. It has been well accepted that CD34+ cell count in peripheral blood before leukapheresis is the best parameter to predict CD34 cell yield. However, white blood cell count, mononuclear cell count, and other easily obtained parameters are still used to guide the clinical practice of peripheral blood stem cell mobilization and collection. Materials and Methods: In the present study, we analyzed the correlation between peripheral blood MNC and Apheresis CD34 levels and also between peripheral blood CD34 by flow cytometry and apheresis CD34 levels. Results: We found that there was a statistically insignificant weak correlation between peripheral MNC and apheresis CD34. There was a statistically significant strong correlation between peripheral CD34 and apheresis CD34. Conclusion: The results show that peripheral blood MNC was analogous indicating that no reliable prediction can be done for CD34 cells collected in apheresis while peripheral CD34 by flow cytometry is the strongest predictor for initiating stem cell collection.


[A surgically resected case of AFP and PIVKA-II producing gastric cancer with hepatic metastasis].
A 78-year-old man was admitted for workup for a liver tumor. Both serum AFP and PIVKA-II levels were high (2260ng/ml and 806mAU/ml, respectively). Contrast-enhanced CT scan and MRI using Gd-EOB-DTPA demonstrated a liver tumor in segment 6 resembling the imaging patterns of hepatocellular carcinoma (HCC), while the upper gastrointestinal endoscopy revealed a type 2 gastric cancer in the gastric antrum. Although the liver metastasis of the gastric cancer was undeniable, we performed partial resection of segment 6 of the liver and distal gastrectomy under a preoperative diagnosis of double cancer. Histopathologically, gastric tumor consisted of two components, such as well differentiated adenocarcinoma and hepatoid adenocarcinoma. The histology of the liver tumor was similar to that of the hepatoid component in the stomach lesion. Immunohistochemical staining revealed both the gastric and the liver tumors to be positive for AFP and PIVKA-II, yielding a definite diagnosis of AFP and PIVKA-II producing gastric cancer with liver metastasis. Because many cases of this disease have liver metastases at presentation with confusing images with HCC, the diagnosis of liver tumors should be carefully differentiated in the gastric cancer patients with liver tumors, high serum AFP and PIVKA-II levels.


Molecular cloning and expression of mouse brain sialidase.
Sialidase (EC 184.108.40.206) catalyzes the release of sialic acid from sialo-oligosaccharides, gangliosides, or sialo-glycoproteins. In this investigation, we cloned a novel cDNA for mouse brain sialidase and expressed the cDNA in COS-7 cells. This 1,699 bp cDNA codes for a 41.6 kDa protein consisting of 372 deduced amino acid residues. In COS-7 cells transiently transfected with the cDNA, a 250-fold increase was observed in specific activity toward 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid. Similarity searches of the nonredundant GenBank peptide sequence database by the PSI-BLAST program identified rat, hamster, human, and bacterial sialidases homologous to this mouse brain sialidase. Amino acid sequence identities to rat and hamster sialidases (84% and 77%, respectively) suggest that this form of sialidase is conserved in rodents. Sequence identities to human and mouse lysosomal sialidases (30% and 28%, respectively) indicate that the mouse brain sialidase is distinct from the lysosomal enzyme. Mouse brain sialidase has two amino acid sequence motifs common to bacterial sialidases: the 'F/YRIP' motif and the 'Asp-box' motif. The 'F/YRIP' motif is present near the N terminus while two 'Asp-box' motifs are present downstream.


Lung transplant for interstitial lung disease: outcomes before and after implementation of the united network for organ sharing lung allocation scoring system.
This study was undertaken to evaluate whether the adoption of the united network for organ sharing lung allocation score (LAS) was associated with significant changes in lung transplantation (LTX) outcomes for patients with interstitial lung disease (ILD) who underwent LTX at the University of Wisconsin Hospital and Clinics. Outcomes for 107 consecutive patients with various forms of ILD who underwent LTX between January 1993 and March 2009 were examined. Patients transplanted following the implementation of the LAS system (LAS, n = 56) were compared with those transplanted prior to LAS implementation (pre-LAS, n = 51) for whom LAS scores were calculated. Patients with idiopathic pulmonary fibrosis (IPF) comprised the majority of patients with ILD. Recipients transplanted after the implementation of the LAS were significantly older (pre-LAS: 50.4 vs. LAS: 56.7 years, P < 0.01), required more supplemental oxygen (3 vs. 5 l/min, P < 0.01) and displayed lower cardiac index values (3.1 vs. 2.6 l/m(2), P < 0.01). The estimated LAS was significantly increased from 38.3 (pre-LAS) to 43.3 (LAS), P < 0.01. However, waiting time decreased from 266 to 78 days (P < 0.01). The rate of bilateral vs. single LTX was lower (35 vs. 16%, P = 0.02) for the post-LAS group. Cold ischaemic time was shorter in the post-LAS group (434 vs. 299 min, P < 0.01), and the length of hospital stay decreased from 24 to 11 days (P < 0.01). Hospital mortality (11 vs. 7%, P = 0.51) and post-transplant survival did not differ between the groups. Post-transplant outcomes for patients with ILD or the subset of recipients with IPF were not adversely affected by the implementation of the LAS.


Treatment of a prolapsed lumbar intervertebral disc in a ferret.
A seven-month-old, male ferret had acute paraplegia and radiographs showed signs of disc prolapse between the second and third lumbar vertebrae (L2/3). Hemilaminectomy was performed to decompress the spinal cord. Histological examination revealed that the extradural material was consistent with annulus fibrosus and the L2/3 articular facets were enlarged as a result of bone remodelling. The ferret became ambulatory one month postoperatively. Five months postoperatively, the ferret had normal posture with mild proprioceptive deficits in the pelvic limbs, and fusion of the L2 and L3 vertebral bodies.


Characterization of a novel light source for simultaneous optical and scanning ion conductance microscopy.
We have developed a novel light source suitable for imaging of biological samples. The method is based on the use of a micropipet filled with fluo-3. A fluorogenic complex is formed when fluo-3 meets calcium in the bath solution. The complex is excited by focusing a laser beam at the pipet tip to produce a submicrometer light source. This source is continually renewed at the tip, eliminating problems with photobleaching, and can be controlled by varying the applied potential. We first characterized the light source using fluorescence correlation measurements in order to optimize its properties. We then recorded an image of a model sample under buffer with submicrometer resolution using ion conductance distance control to demonstrate the feasibility of this approach.


The Herschel-Quincke tube: the attenuation conditions and their sensitivity to mean flow.
The classic Herschel-Quincke tube is a parallel connection of two ducts yielding multiple noise attenuation maxima via destructive interference. This problem has been discussed to different degrees by a number of authors over the years. This study returns to the basics of the system for the purpose of furthering the understanding of the conditions necessary for noise attenuation and especially their sensitivity to mean flow. First, the transmission loss for an N-duct system with mean flow and arbitrary conditions of state in the different ducts is derived. Next, the two types of conditions yielding the attenuation maxima are studied. In addition to a discussion of the underlying physics, generic expressions for frequencies at which maximum attenuation occur are presented. Experiments without mean flow generally show good agreement with theory based on straight duct elements. However, more detailed models may be required for accurate simulations in the presence of mean flow. A simple model compensating for the losses associated with bends is shown to improve the results significantly for the geometry studied.


Anterior Cruciate Ligament Reconstruction: Is Biological Augmentation Beneficial?
Surgical reconstruction in anterior cruciate ligament (ACL) ruptures has proven to be a highly effective technique that usually provides satisfactory results. However, despite the majority of patients recovering their function after this procedure, ACL reconstruction (ACLR) is still imperfect. To improve these results, various biological augmentation (BA) techniques have been employed mostly in animal models. They include: (1) growth factors (bone morphogenetic protein, epidermal growth factor, granulocyte colony-stimulating factor, basic fibroblast growth factor, transforming growth factor-β, hepatocyte growth factor, vascular endothelial growth factor, and platelet concentrates such as platelet-rich plasma, fibrin clot, and autologous conditioned serum), (2) mesenchymal stem cells, (3) autologous tissue, (4) various pharmaceuticals (matrix metalloproteinase-inhibitor alpha-2-macroglobulin bisphosphonates), (5) biophysical/environmental methods (hyperbaric oxygen, low-intensity pulsed ultrasound, extracorporeal shockwave therapy), (6) biomaterials (fixation methods, biological coatings, biosynthetic bone substitutes, osteoconductive materials), and (7) gene therapy. All of them have shown good results in experimental studies; however, the clinical studies on BA published so far are highly heterogeneous and have a low degree of evidence. The most widely used technique to date is platelet-rich plasma. My position is that orthopedic surgeons must be very cautious when considering using PRP or other BA methods in ACLR.


In situ phase transitional polymeric vaccines for improved immunotherapy.
Cancer vaccines have exhibited immense potential in cancer treatment. Through activating the host's immune system, vaccines stimulate extensive functional T cells to eliminate cancer. However, the therapeutic efficacy of cancer vaccines is limited by their inferior lymph node delivery and inadequate uptake of dendritic cells. Herein, we propose an in situ phase transitional strategy on vaccine manufacturing to maximally enhance lymph node drainage while ensuring adequate dendritic cell uptake. The phase transitional vaccines, with dynamic size modulation property, retain a small size (24.4 ± 3.1 nm) during lymph node draining then transform into larger particles (483.0 ± 41.6 nm) on-site by external signal input. Results show that this strategy induced rapid and robust immune response in a mouse melanoma tumor model. Furthermore, a stronger humoral immune response was observed in mice when immunized with MHC-II restricted antigen, which demonstrated that lymph node-targeted cancer vaccine delivery could be effectively manipulated through dynamic size modulation.


A new missense variant in RAB3GAP2 in a family with muscular dystrophy-short stature and defective autophagy: An expansion of the micro/Martsolf spectrum or a new phenotype?
We describe a sibling pair of Mennonite origin born from consanguineous parentage with a likely new phenotype of limb-girdle muscular dystrophy, short stature, ptosis, and tracheomalacia. Exome sequencing in the affected subjects identified a novel homozygous RAB3GAP2 missense variant as the potential causal variant. As RAB3GAP2 has been recently shown to be involved in the autophagy process, we analyzed patient-derived fibroblasts by fluorescence microscopy and demonstrated defective autophagic flux under rapamycin and serum starvation conditions when compared with wild-type cells. The phenotype in the siblings described here is distinct from Martsolf and Warburg's micro syndromes, the currently known diseases arising from RAB3GAP2 pathogenic variants. Thus, this work describes a potentially novel recessive phenotype associated with a RAB3GAP2 defect and manifesting as a muscular dystrophy-short stature disorder with no ocular anomalies. Functional analyses indicated defective autophagy in patient-derived fibroblasts, supporting the involvement of RAB3GAP2 in the etiology of this disorder. Our results contribute to a better characterization of the Martsolf/micro spectrum phenotype.


Three interferometric methods for measuring the thickness of layers of the tear film.
The thickness of different layers of the tear film has been measured by three types of interference method, namely, wavelength-dependent fringes (WDFs), thickness-dependent fringes (TDFs), and angle-dependent fringes (ADFs). This review begins with a discussion of characteristics which are common to all these methods--high-, intermediate-, and low-index layers, phase, optical path difference, and contrast. For each of the three methods, we present a figure showing constructive and destructive interference, derive equations for calculating tear layer thickness, describe a typical optical system, and show representative results. The particular advantages and limitations of each method are discussed. Given the clinical importance of the tear film in dry eye syndrome and contact lens wear, it is unfortunate that there are considerable discrepancies among the results of interferometric and other methods for measuring tear film thickness; further development of these noninvasive, interferometric methods should help to provide a clearer picture of the thickness of different layers of the tear film, in normal and dry eyes, and in contact lens wear.


The future of the PA profession. Panel discussion.
Growth and opportunity are the catchwords for the PA profession into the 1990s. Numerous changes can be expected, along with stimulating new challenges. Concern about the survival of the profession has waned. Current focus is on expansion of the profession to meet demands of America's changing health care delivery system. A distinguished panel of PA leaders discusses such issues as diversity within the profession, growth of hospital-based PAs, HMOs, public policy, PA education, the growing job market, and expanding roles of PAs.


Predictors of an Extended Length of Stay following an Elective Craniotomy in Children and Young Adults.
Length of stay (LOS) is now a generally accepted clinical metric within the USA. An extended LOS following an elective craniotomy can significantly impact overall costs. Few studies have evaluated predictors of an extended LOS in pediatric neurosurgical patients. The aim of the study was to determine predictors of an extended hospital LOS following an elective craniotomy in children and young adults. All pediatric patients and young adults undergoing an elective craniotomy between January 1, 2010, and April 1, 2019, were retrospectively identified using a prospectively maintained database. Demographic, clinical, radiological, and surgical data were collected. The primary outcome was extended LOS, defined as a postsurgical stay greater than 7 days. Bivariate and multivariable analyses were performed. A total of 1,498 patients underwent 1,720 elective craniotomies during the study period over the course of 1,698 hospitalizations with a median LOS of 4 days (interquartile range 3-6 days). Of these encounters, 218 (12.8%) had a prolonged LOS. Multivariable analysis demonstrated that non-Caucasian race (OR = 1.9 [African American]; OR = 1.6 [other]), the presence of an existing shunt (OR = 1.8), the type of craniotomy (OR = 0.3 [vascular relative to Chiari]), and the presence of a postoperative complication (OR = 14.7) were associated with an extended LOS. Inherent and modifiable factors predict a hospital stay of more than a week in children and young adults undergoing an elective craniotomy.


Correlation of middle cerebral artery tortuosity with successful recanalization using the Merci retrieval system with or without adjunctive treatments.
The Merci retrieval system is a useful modality for the recanalization of acute cerebral artery occlusion. However, it remains unclear whether the tortuosity of the middle cerebral artery (MCA) plays a role in successful recanalization. In this study, we investigated the association between the shape of the horizontal MCA segment (M1) and successful recanalization using the Merci retrieval system with or without adjunctive treatments. Twenty-three patients with M1 occlusion underwent thrombectomy using the Merci retrieval system with or without adjunctive treatments between July 2010 and July 2012. The anteroposterior view of final angiograms was used to measure the M1 curve angles. M1 with a curve angle measuring < 100° was defined as arch-type M1, whereas that with a curve angle measuring ≥ 100° was defined as straight-type M1. Angiographic findings were evaluated on the basis of the thrombolysis in cerebral infarction grade; grade 2B or 3 corresponds to successful recanalization. Eight patients had arch-type M1 and 15 patients had straight-type M1. Successful recanalization was achieved in 2 patients (25%) with arch-type M1 and 12 patients (80%) with straight-type M1 (p = 0.023). The mean M1 curve angle was significantly greater in the 14 patients in whom successful recanalization was achieved than in the 9 patients in whom it was not achieved (129 ± 21° vs. 93 ± 29°, p = 0.002). Arch-type M1 was an independent predictive factor of unsuccessful recanalization (odds ratio, 0.045; 95% confidence interval, 0.03-0.696). A tortuous M1 was associated with unsuccessful recanalization by the Merci retrieval system, even when adjunctive treatments were used.


Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies.
Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of -0.334 μg/ml (95% CI, -0.465 to -0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of -0.502 μg/ml (95% CI, -0.957 to -0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.


Prescribing medicinal cannabis.
The Australian Federal Government legalised access to medicinal cannabis in 2016 More than 100 different cannabis products are now available to prescribe. Most are oral preparations (oils) or capsules containing delta-9-tetrahydrocannabinol or cannabidiol. Dried-flower products are also available As most products are unregistered drugs, prescribing requires approval under the Therapeutic Goods Administration Special Access Scheme-B or Authorised Prescriber Scheme Special Access Scheme Category B applications can be made online, with approval usually being given within 24–48 hours. However, supply chain problems may delay dispensing by the pharmacy By the end of 2019, over 28,000 prescribing approvals had been issued to patients, involving more than 1400 doctors, mostly GPs. More than 70,000 approvals are projected by the end of 2020 Most prescriptions are for chronic non-cancer pain, anxiety, cancer-related symptoms, epilepsy and other neurological disorders. However, the evidence supporting some indications is limited Many doctors are cautious about prescribing cannabis. While serious adverse events are rare, there are legitimate concerns around driving, cognitive impairment and drug dependence with products containing delta-9-tetrahydrocannabinol. Cannabidiol-only products pose fewer risks


Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo.
We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells. The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined. IFN-alphaCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1microg/mouse/day resulted in 26%, and 1 microg/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-alphaCon1 dose. IFN-alphaCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-alphaCon1 in the prevention and treatment of HCC.


The Oxidative Potential of Fine Particulate Matter and Biological Perturbations in Human Plasma and Saliva Metabolome.
Particulate oxidative potential may comprise a key health-relevant parameter of particulate matter (PM) toxicity. To identify biological perturbations associated with particulate oxidative potential and examine the underlying molecular mechanisms, we recruited 54 participants from two dormitories near and far from a congested highway in Atlanta, GA. Fine particulate matter oxidative potential ("FPMOP") levels at the dormitories were measured using dithiothreitol assay. Plasma and saliva samples were collected from participants four times for longitudinal high-resolution metabolic profiling. We conducted metabolome-wide association studies to identify metabolic signals with FPMOP. Leukotriene metabolism and galactose metabolism were top pathways associated with ≥5 FPMOP-related indicators in plasma, while vitamin E metabolism and leukotriene metabolism were found associated with most FPMOP indicators in saliva. We observed different patterns of perturbed pathways significantly associated with water-soluble and -insoluble FPMOPs, respectively. We confirmed five metabolites directly associated with FPMOP, including hypoxanthine, histidine, pyruvate, lactate/glyceraldehyde, and azelaic acid, which were implications of perturbations in acute inflammation, nucleic acid damage and repair, and energy perturbation. The unique metabolic signals were specific to FPMOP, but not PM mass, providing initial indication that FPMOP might constitute a more sensitive, health-relevant measure for elucidating etiologies related to PM2.5 exposures.


Residential exposure to power frequency magnetic field and sleep disorders among women in an urban community of northern Taiwan.
To investigate relationships between residential exposure to power frequency magnetic field and sleep initiation and maintenance disorders (SIAMD). A cross-sectional design conducted in an urban town of northern Taiwan in 1995-1996. A total of 5,078 married women aged 20-59. N/A. The residential magnetic field intensity was assessed using EMDEX II dosimeters. Trained interviewees collected self-reported information on SIAMD and other covariates. Three type-specific SIAMD were analyzed for associations with background, bedroom, and overall residential exposures. The prevalence rates of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) were 29.5%, 38.17%, and 26.02%, respectively. The DIS prevalence was significantly associated with bedroom magnetic field exposure of 2 miliGauss (mG) (odds ratio (OR)=1.20, 95% confidence interval (CI)=1.02-1.40). The DMS prevalence was significantly higher for women with background exposure of 2 mG (OR=1.28, 95% CI=1.04-1.56). An elevated EMA prevalence was also significantly associated with all of the three exposure measures with excess risks ranging from 28% for overall exposure to 65% for background exposure. When magnetic field strength was analyzed as a continuous variable, background exposure, but not overall or bedroom exposure, showed a small but significant association with DMS and EMA (OR=1.05 per 1 mG increase, 95% CI=1.02-1.09). There is a modest association between residential exposures to elevated magnetic field intensity and insomnia complaints in women.


L1-associated genomic regions are deleted in somatic cells of the healthy human brain.
The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associated variants (SLAVs) are composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants. We demonstrate that a subset of SLAVs comprises somatic deletions generated by L1 endonuclease cutting activity. Retrotransposition-independent rearrangements in inherited L1s resulted in the deletion of proximal genomic regions. These rearrangements were resolved by microhomology-mediated repair, which suggests that L1-associated genomic regions are hotspots for somatic copy number variants in the brain and therefore a heritable genetic contributor to somatic mosaicism. We demonstrate that SLAVs are present in crucial neural genes, such as DLG2 (also called PSD93), and affect 44-63% of cells of the cells in the healthy brain.


Cellular and molecular dynamics in the foreign body reaction.
Intracorporally implanted materials, such as medical devices, will provoke the body to initiate an inflammatory reaction. This inflammatory reaction to implanted materials is known as the foreign body reaction (FBR) and is characterized by 3 distinct phases: onset, progression, and resolution. The FBR proceeds in the creation of a dynamic microenvironment that is spatially well organized. The progression of the FBR is regulated by soluble mediators, such as cytokines, chemokines, and matrix metalloproteinases (MMPs), which are produced locally by tissue cells and infiltrated inflammatory cells. These soluble mediators orchestrate the cascade of cellular processes in the microenvironment that accompanies the FBR, consisting of cellular activation, angiogenesis, extravasation, migration, phagocytosis, and, finally, fibrosis. The nature of the FBR requires that the soluble mediators act in a spatial and temporally regulated manner as well. This regulation is well known for several inflammatory processes, but scarce knowledge exists about the intricate relationship between the FBR and the expression of soluble mediators. This review discusses the key processes during the initiation, progression, and resolution phase, with emphasis on the role of soluble mediators. Besides other sites of implantation, we focus on the subcutaneous implantation model.


Targeted imaging and proteomic analysis of tumor-associated glycans in living animals.
Although it has been well known that dynamic changes in glycosylation are associated with tumor progression, it remains challenging to selectively visualize the cancer glycome in vivo. Herein, a strategy for the targeted imaging of tumor-associated glycans by using ligand-targeted liposomes encapsulating azidosugars is described. The intravenously injected liposomal nanoparticles selectively bound to the cancer-cell-specific receptors and installed azides into the melanoma glycans in a xenograft mouse model in a tissue-specific manner. Subsequently, a copper-free click reaction was performed in vivo to chemoselectively conjugate the azides with a near-infrared fluorescent dye. The glycosylation dynamics during tumor growth were monitored by in vivo fluorescence imaging. Furthermore, the newly synthesized sialylated glycoproteins were enriched during tumor growth and identified by glycoproteomics. Compared with the labeling methods using free azidosugars, this method offers improved labeling efficiency and high specificity and should facilitate the elucidation of the functional role of glycans in cancer biology.


Ultrafast Dynamics at Lipid-Water Interfaces.
Lipid membranes are more than just barriers between cell compartments; they provide molecular environments with a finely tuned balance between hydrophilic and hydrophobic interactions that enable proteins to dynamically fold and self-assemble to regulate biological function. Characterizing dynamics at the lipid-water interface is essential to understanding molecular complexities from the thermodynamics of liquid-liquid phase separation down to picosecond-scale reorganization of interfacial hydrogen-bond networks.Ultrafast vibrational spectroscopy, including two-dimensional infrared (2D IR) and vibrational sum-frequency generation (VSFG) spectroscopies, is a powerful tool to examine picosecond interfacial dynamics. Two-dimensional IR spectroscopy provides a bond-centered view of dynamics with subpicosecond time resolutions, as vibrational frequencies are highly sensitive to the local environment. Recently, 2D IR spectroscopy has been applied to carbonyl and phosphate vibrations intrinsically located at the lipid-water interface. Interface-specific VSFG spectroscopy probes the water vibrational modes directly, accessing H-bond strength and water organization at lipid headgroup positions. Signals in VSFG arise from the interfacial dipole contributions, directly probing headgroup ordering and water orientation to provide a structural view of the interface.In this Account we discuss novel applications of ultrafast spectroscopy to lipid membranes, a field that has experienced significant growth over the past decade. In particular, ultrafast experiments now offer a molecular perspective on increasingly complex membranes. The powerful combination of ultrafast, interface-selective spectroscopy and simulations opens up new routes to understanding multicomponent membranes and their function. This Account highlights key prevailing views that have emerged from recent experiments: (1) Water dynamics at the lipid-water interface are slow compared to those of bulk water as a result of disrupted H-bond networks near the headgroups. (2) Peptides, ions, osmolytes, and cosolvents perturb interfacial dynamics, indicating that dynamics at the interface are affected by bulk solvent dynamics and vice versa. (3) The interfacial environment is generally dictated by the headgroup structure and orientation, but hydrophobic interactions within the acyl chains also modulate interfacial dynamics. Ultrafast spectroscopy has been essential to characterizing the biophysical chemistry of the lipid-water interface; however, challenges remain in interpreting congested spectra as well as designing appropriate model systems to capture the complexity of a membrane environment.


In Situ Intrinsic Self-Healing of Low Toxic Cs2 ZnX4 (X = Cl, Br) Metal Halide Nanoparticles.
This study reports on the intrinsic and fast self-healing ability of all inorganic, low-toxic Cs2 ZnX4 (X = Cl, Br) metal halide nanoparticles (NPs) when subjected to local heating by electron beam irradiation in high-resolution transmission electron microscopy (HR-TEM). The local heating induces the creation of nanoshells (NSs) following the template of the corresponding NPs, which are subsequently healed back to their original state within several minutes. Energy dispersive spectroscopy (EDS) and fast Fourier transform (FFT) analysis reveal that the composition, phase, and crystallographic structure of the original NPs are restored during the self-healing process, with a thin crystalline layer observed at the bottom of the NSs acting as the healing template. The inelastic scattering of the electron beam energy generates local heat that causes rapid atomic displacement, resulting in atomic mobility that lowers the density of the material and leads to NS formation. A unique insitu TEM heating stage measurement demonstrates the appearance of identical damage and self-healing to those induced by the electron beam. The NPs exhibit excellent stability under ambient conditions for up to a month, making them suitable for self-healing scintillators and other optoelectronic applications that require atomic-scale stability and healing.


Anti-Factor H Antibodies in Egyptian Children with Hemolytic Uremic Syndrome.
Atypical hemolytic uremic syndrome (aHUS) is an important cause of acute kidney injury in children. It is primarily caused by dysregulation of the complement alternative pathway due to genetic mutations, mainly in complement factor H genes, or due to anti-factor H autoantibodies (anti-FH), leading to uncontrolled overactivation of the complement system. Early diagnosis and treatment of autoimmune HUS (AI-HUS) is essential and leads to a favorable outcome. Fifty pediatric HUS patients and 50 age- and sex-matched controls were included in the study. Patients were subjected to full history taking, clinical examination, and laboratory testing. All candidates were subjected to an assessment of anti-FH in serum by a homemade enzyme-linked immunosorbent assay technique. A high frequency of serum anti-FH was detected in our aHUS patients. The disease onset of AI-HUS was mainly observed in March and April, with significantly higher rates in school-aged males. All patients who started immunosuppressives early together with plasmapheresis upon detection of their anti-FH had complete renal function recovery. The high frequency of AI-HUS revealed in Egyptian HUS children in our study highlights the importance of implementing anti-FH testing in Egypt to provide early recognition for immediate proper management, including early immunosuppressive therapy, and hence improving patient outcomes.


Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction.
Preoperative left ventricular systolic function is an important predictor of postoperative prognosis in patients with aortic regurgitation. Although left ventricular dysfunction is reversible after aortic valve replacement to a greater extent in patients with good preoperative exercise capacity compared with patients with impaired exercise capacity, not all patients with preserved exercise capacity demonstrate improved left ventricular function after aortic valve replacement. To determine the influence of duration of preoperative left ventricular dysfunction on postoperative reversal of left ventricular dysfunction, we studied 37 patients with aortic regurgitation who preoperatively had left ventricular dysfunction, defined as subnormal echocardiographic fractional shortening (less than 29%), and good preoperative exercise capacity, defined as completion of stage I of the NIH treadmill protocol without limiting symptoms. Eight patients were asymptomatic. In 11 patients left ventricular dysfunction was documented 18 to 57 months preoperatively (prolonged); in 10 patients left ventricular dysfunction developed in an interval of 14 months or less preoperatively (brief); in 16 patients duration of left ventricular dysfunction was unknown. Patients with brief vs those with prolonged left ventricular dysfunction did not differ with respect to severity of preoperative symptoms or exercise tolerance, echocardiographically determined left ventricular dimensions or fractional shortening (25 +/- 3% [SD] vs 25 +/- 3%), or radionuclide angiographic ejection fraction (42 +/- 5% vs 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of antitumor activities of 2-chlorodeoxyadenosine and 9-beta-arabinosyl-2-fluoroadenine in chronic lymphocytic leukemia and marrow cells in vitro.
The in vitro antitumor activities of the nucleoside analogs, 2-chlorodeoxyadenosine (CdA) and 9-beta-arabinosyl-2-fluoroadenine monophosphate (Flu), and the alkylating agent, chlorambucil (CLB), were compared in leukemic cells from 28 patients with chronic lymphocytic leukemia (CLL). On a molar basis, the median sensitivities of the cells to these agents were CLB > CdA > Flu. CLL cells from 90% of the patients had similar relative orders of sensitivities to CdA and Flu, while cells from 10% of the patients showed differential sensitivities to these agents. There was no relationship between the sensitivities of the cells to the nucleoside analogs and sensitivity to CLB. CdA and CLB produced similar toxicities to human marrow progenitor cells in vitro, while Flu was less toxic to these cells. An 18 h exposure to CdA produced significantly greater cell kill of both CLL and marrow progenitor cells than an equivalent 2 h treatment; however, the difference in cytotoxicity was greater for the tumor cells resulting in a higher therapeutic index with the 18 h treatment. The intracellular accumulation of drug varied 5-fold for CdA, with the major metabolite being CdAMP, and 15-fold for Flu, with the major metabolite being F-ara-ATP. However, the accumulation of CdA, Flu or their metabolites did not predict for drug sensitivity. These studies suggest that CdA and Flu cross-resistance cannot be assumed in all CLL patients. The therapeutic effectiveness of CdA may be enhanced by use of a prolonged, low-dose drug regimen.


Turkish Adaptation of the Positive-Negative Relationship Quality (PN-RQ) Scale: A Reliability and Validity Study.
The present study investigates the reliability and validity of the Positive-Negative Relationship Quality (PN-RQ) scale in Turkey. This study aims to test different factorial models including orthogonal factors model, correlated factors model, one-factor model, and bifactor model. In order to determine the validity and reliability of the scale, two studies were performed. The first was carried out with emerging adults (university students) who were in a romantic relationship (148 females, 43 males, and 2 unknown) and had the main purpose to examine the structure validity of the measurement tool in the Turkish sample with an exploratory analysis. Study 2 was performed online with 513 married adults (359 females, 149 males, and 5 unknown); confirmatory findings and criterion validity studies were added. Exploratory factor analyses revealed that relationship quality had a two-factor structure and that there was also a negative relationship between the factors. Confirmatory factor analyses on the married sample showed that the bi-factor model provided evidence for the multidimensional nature of the scale. Both studies demonstrated high internal consistency. There is evidence for reliability and validity in the Turkish version of the PN-RQ scale to measure both positive and negative aspects of the relationship. The PN-RQ scale will be highly functional for social and clinical psychologists who work on close relationship issues in Turkey.


The dilemma of good clinical practice in the study of compromised standards of care.
Four ethical issues loom over the study by Lieberman and colleagues--the absence of informed consent, the study being non-interventional in situations that typically call for life-saving interventions, the bias involved in doctors that study their own problematic practice and monopoly over intensive care unit triage, and ageism. We learn that the Israeli doctors in this study never make no-treatment decisions regarding patients in need of mechanical ventilation. They are complicit with botched standards of care for these patients, however, accepting without much doubt an ethos of scarce resources and poor managerial habits. The main two practical lessons to be taken from this study are that, for patients in need of mechanical ventilation, compromised care is better than a policy of intubation only when the intensive care unit is available, and that vigorous efforts are needed in order to extirpate ageism.


Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation.
We sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies. We conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response. Sixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response). ICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.