A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: characterization, dissolution, in vitro digestion and incorporation into solid pellets.
The aim of the current study was the development of a new pellet based self-emulsifying (SE) drug delivery system for the oral delivery of poorly soluble drugs. Furthermore, we wanted to investigate the influence of physiological dilution media and enzymatic digestion on the solubilization capacity of the formulation for the model drug Progesterone. Lipid mixtures composed of Solutol HS 15 and medium chain glycerides were optimized with respect to their self-emulsifying properties. The liquid SE lipid was mixed with microcrystalline cellulose and transformed into pellets by extrusion/spheronization. The pellets were characterized for size, shape, surface characteristics and friability. In vitro dissolution and digestion experiments were carried out using physiological dissolution media. The droplet diameter of the dispersed SE mixtures was largely affected by changing the oil to Solutol HS 15 ratio. Moreover, digestion of SE mixtures changed the solubilization capacity for Progesterone. Pellets with good properties (size, shape and friability) have been produced through the incorporation of a selected SE mixture into MCC. In conclusion, extrusion/spheronization is a suitable process to produce solid self-emulsifying pellets with up to 40% load of a liquid SE mixture. Digestion induces a change in lipid composition which affects the solubilization capacity of the lipid phase.


Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases: a key component in pathways of phosphoinositide turnover.
Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (α and β isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 μM and 1.02 μM, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant change in helicity upon binding with EGCG. EGCG modulates its effect by interacting with ATP binding pocket; the residues likely to be involved in EGCG binding were predicted by Autodock. Our findings suggest that EGCG inhibits two isoforms and could be a key to regulate T cell activation.


Spectroscopic properties of fluoroquinolone antibiotics in water-methanol and water-acetonitrile mixed solvents.
The fluorescence properties of ofloxacin (OFL), norfloxacin (NOR) and flumequine (FLU) were studied in H2O-CH3OH and H2O-CH3CN mixed solvents because these solvents were thought to behave as a biological mimetic system. The emission spectra of OFL and NOR were very sensitive to the composition of the solvents. In the Lippert-Mataga analysis of the steady-state fluorescence data of OFL and NOR, clear reverse solvatochromism was exhibited in both mixed solvents. This observation can be explained by the twisted excited-state intramolecular charge transfer, which is accelerated by water. Theoretical treatments further support these results. The radiative and nonradiative rate constants were analyzed as a function of solvent dipolarity-polarizability (pi*) and hydrogen-bond donor acidity (alpha). These results were well consistent with the suggested mechanism of the excited-state chemical process of OFL and NOR, which depended upon the solvent-solute interactions such as bulk dielectric effects and specific hydrogen-bonding interactions. However, the influence of dielectric effects was more significant. The solvent structures of H2O-CH3CN and the preferential solvation by water were also examined. The emission spectra of FLU do not exhibit any characteristic responses to the properties of the environment.


Does the supervisor's teaching style influence the supervisee's learning prescribed techniques?
This study examined the directive and non-directive supervisors' instructional styles, supervisees' interactive communications within supervision sessions as well as the relative success of supervisees' learning to apply specific techniques within psychotherapy. The developers of Time-Limited Dynamic Psychotherapy (TLDP) provided the supervised training for 16 therapists as part of the "Vanderbilt II" psychotherapy project. Supervision sessions were rated for supervisors' adherence to TLDP content. Both supervisors and supervisee were rated for classroom interactive behaviors of "initiation" speech (e.g., introducing ideas) and "responsive" speech (e.g., amplifying the other speaker's topic). The third therapy session was targeted for discussion within supervision. Therapy sessions immediately before and after supervision were rated on TLDP adherence. One of the supervisors (Supervisor A) was found to use an instructional style of relatively more initiation-based speech, whereas the other (Supervisor B) used more response-based speech. Technical adherence for supervisees of Supervisor A was significantly higher than those assigned to Supervisor B. Supervisees' initiation-based speech during supervision predicted less use of TLDP techniques in the therapy session after supervision. Supervisors' interactive style was not associated with therapy adherence. Relatively more directive and structured supervision may influence the acquisition and use of manual-prescribed therapy techniques.


Characterization of the distribution of G alpha o in rat striatal synaptosomes and its colocalization with tyrosine hydroxylase.
Dopaminergic striatal synaptosomes can be detected and isolated with a fluorescence-activated cell sorter (FACS). In the present study, two antigens were detected simultaneously with primary antisera raised in different species and species-specific fluorescent secondary antibodies with different emission spectra. Double-label FACS analysis was used to determine whether tyrosine hydroxylase (TH) and the alpha subunit of Go (G alpha o) are colocalized in striatal synaptosomes. Rabbit antibodies generated against a synthetic fragment of G alpha o (corresponding to amino acids 22-35) combined with fluorescein-conjugated secondary antibodies were used to detect G alpha o-containing striatal synaptosomes. Preadsorption of G alpha o antiserum with the synthetic peptide antigen reduced labeling to the level obtained with preimmune serum. Approximately 65-75% of striatal synaptosomes were specifically labeled by G alpha o antiserum. Tyrosine hydroxylase-containing synaptosomes were detected with a mouse monoclonal antibody to TH and R-phycoerythrin-conjugated secondary antibody. They comprised 15-17% of total striatal synaptosomes. Double-label studies indicated that at least 50% of TH-containing synaptosomes also contained G alpha o. These findings suggest that G alpha o may not be a protein component of all striatal nerve terminals, and provide a basis for a role for G alpha o in signal transduction within subpopulations of intrinsic and afferent nerve terminals, including those of nigrostriatal dopamine neurons.


Coronary and microvascular physiology during intra-aortic balloon counterpulsation.
This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.


Comparison of the protein content of free and membrane-bound rat liver polysomes and of the derived subunits.
Ribosomal proteins from pure free and membrane-bound rat liver polysomes were analyzed with a highly resolutive two-dimensional gel electrophoresis technique, using sodium dodecyl sulfate in the second dimension. Three acidic proteins found in free polysomes were always absent from the membrane-bound polysomes. Their molecular weights were estimated to be 20 000, 19 500 and 18 500. When free ribosomes were dissociated into subunits, the three protein spots were still found in the 60S subunit pattern, but they were weaker than in polysomes. A possible involvement of these three proteins in the attachment of ribosomal structures to the membranes is proposed.


The "Hockey" Assist Makes the Difference-Validation of a Defensive Disruptiveness Model to Evaluate Passing Sequences in Elite Soccer.
With the growing availability of position data in sports, spatiotemporal analysis in soccer is a topic of rising interest. The aim of this study is to validate a performance indicator, namely D-Def, measuring passing effectiveness. D-Def calculates the change of the teams' centroid, centroids of formation lines (e.g., defensive line), teams' surface area, and teams' spread in the following three seconds after a pass and therefore results in a measure of disruption of the opponents' defense following a pass. While this measure was introduced earlier, in this study we aim to prove the usefulness to evaluate attacking sequences. In this study, 258 games of Dutch Eredivisie season 2018/19 were included, resulting in 13,094 attacks. D-Def, pass length, pass velocity, and pass angle of the last four passes of each attack were calculated and compared between successful and unsuccessful attacks. D-Def showed higher values for passes of successful compared to unsuccessful attacks (0.001 < p ≤ 0.029, 0.06 ≤ d ≤ 0.23). This difference showed the highest effects sizes in the penultimate pass (d = 0.23) and the maximal D-Def value of an attack (d = 0.23). Passing length (0.001 < p ≤ 0.236, 0.08 ≤ d ≤ 0.17) and passing velocity (0.001 < p ≤ 0.690, -0.09 ≤ d ≤ 0.12) showed inconsistent results in discriminating between successful and unsuccessful attacks. The results indicate that D-Def is a useful indicator for the measurement of pass effectiveness in attacking sequences, highlighting that successful attacks are connected to disruptive passing. Within successful attacks, at least one high disruptive action (pass with D-Def > 28) needs to be present. In addition, the penultimate pass ("hockey assist") of an attack seems crucial in characterizing successful attacks.


Analgesic and cardiopulmonary effects of premedication with tramadol in calves anesthetized with the infusion of guaifenesin and thiamylal.
This study examined the analgesic and cardiopulmonary effects of intravenous (IV) tramadol during general intravenous anesthesia in calves. Calves were premedicated with diazepam (0.2 mg/kg, IV) with tramadol (2 mg/kg, IV) (group T) or saline (group S). Anesthesia was induced by thiamylal sodium (4 mg/kg, IV) and maintained with an infusion (2 ml/kg/hr) of 5% guaifenesin containing thiamylal sodium (2 mg/ml). Additional thiamylal sodium (1-2 mg/kg, IV) was administered when interference from the calves was observed during surgery. The total counts of additional thiamylal sodium administration, analgesia score using a visual analog scale, recovery time, and cardiopulmonary function in the different groups were assessed and compared. Group T showed significantly fewer counts of additional drug administration and a significantly higher analgesia score. Tramadol may provide adequate analgesia with minimal cardiopulmonary changes in calves during general anesthesia.


Effect of parathyroidectomy on plasma calcium levels in the seal salamander, Desmognathus monticola.
The parathyroid glands of Desmognathus monticola are located in the subdermal connective tissue of the neck. Although they are smaller than previously described urodele parathyroid glands, their histological structure is similar. Parathyroidectomy caused a decrease in plasma calcium concentrations within 4 days following the operation. By Days 12 and 21, however, the plasma calcium levels of parathyroidectomized animals were not significantly different from those of sham-operated animals. Thus, the parathyroid gland of this species contains a hypercalcemic principle, but the recovery from hypocalcemia suggests that some hypercalcemic mechanism other than the parathyroid system must be involved in calcium homeostasis.


The Conformation of the Intrinsically Disordered N-Terminal Region of Barrier-to-Autointegration Factor (BAF) is Regulated by pH and Phosphorylation.
Barrier-to-Autointegration Factor (BAF) is a highly conserved DNA binding protein important for genome integrity. Its localization and function are regulated through phosphorylation. Previously reported structures of BAF suggested that it is fully ordered, but our recent NMR analysis revealed that its N-terminal region is flexible in solution and that S4/T3 di-phosphorylation by VRK1 reduces this flexibility. Here, molecular dynamics (MD) simulation was used to unveil the conformational ensembles accessible to the N-terminal region of BAF either unphosphorylated, mono-phosphorylated on S4 or di-phosphorylated on S4/T3 (pBAF) and to reveal the interactions that contribute to define these ensembles. We show that the intrinsic flexibility observed in the N-terminal region of BAF is reduced by S4 phosphorylation and to a larger extent by S4/T3 di-phosphorylation. Thanks to the atomic description offered by MD supported by the NMR study of several BAF mutants, we identified the dynamic network of salt bridge interactions responsible for the conformational restriction involving pS4 and pT3 with residues located in helix α1 and α6. Using MD, we showed that the flexibility in the N-terminal region of BAF depends on the ionic strength and on the pH. We show that the presence of two negative charges of the phosphoryl groups is required for a substantial decrease in flexibility in pBAF. Using MD supported by NMR, we also showed that H7 deprotonation reduces the flexibility in the N-terminal region of BAF. Thus, the conformation of the intrinsically disordered N-terminal region of BAF is highly tunable, likely related to its diverse functions.


Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall-Stickler syndrome spectrum.
Marshall-Stickler syndrome represents a spectrum of inherited connective tissue disorders affecting the ocular, auditory, and skeletal systems. The syndrome is caused by mutations in the COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 genes. In this study, we examined four Turkish families with Marshall-Stickler syndrome using whole-exome sequencing and identified one COL2A1 mutation and three COL11A1 mutations. Two of the COL11A1 mutations were novel. Our findings expand our knowledge of the COL11A1 mutational spectrum that causes Marshall-Stickler syndrome.


Stochastic method for accommodation of equilibrating basins in kinetic Monte Carlo simulations.
A computationally simple way to accommodate 'basins' of trapping states in standard kinetic Monte Carlo simulations is presented. By assuming that the system is effectively equilibrated in the basin, the residence time (time spent in the basin before escape) and the probabilities for transitions to states outside the basin may be calculated. This is demonstrated for point defect diffusion over a periodic grid of sites containing a complex basin.


Development and Psychometric Evaluation of a Socioeconomic Status Questionnaire for Urban Households (SESIran): The Preliminary Version.
The aim of present study was to develop and validate an appropriate socioeconomic status (SES) assessment questionnaire to be used through health studies in Iranian urban households. The study was conducted through a mixed method study design in Tabriz, northwest of Iran in 2014. It was conducted in several stages including: development of initial version, qualitative study, feasibility evaluation, and assessment of the validity as well as the reliability. The internal consistency, test-retest reliability, content validity, concurrent validity and construct validity were assessed. With respect to the assessment of construct validity, 5 domains (factors) were extracted includ-ing: main factor (α=0.84), self-evaluation of expenditure capacity (α=0.96), wealth (α=0.70), home and furniture (α=0.66) and costs related to health (α=0.55). Intraclass correlation coefficient was above 0.6 for all factors except for wealth domain. The questionnaire developed appeared to be a valid and reliable SES assessment tool. It may be of value to be used not only as a complementary questionnaire in most health surveys or clini-cal studies, but also as a main questionnaire in health equity and health economics research.


Body size, ration level, and population growth in Asplanchna.
1.) The daily ration required to maintain a population growth rate, r m, of zero (threshold ration) increased with increasing Asplanchna body mass. This relationship is described by the equation T=0.342 W0.797 where T=threshold ration (μg day-1 dry mass) and W=Asplanchna body mass (μg adult-1 dry mass). 2.) The threshold ration of large campanulate morphs of A. silvestrii was 3.7 times greater than that of conspecific saccate morphs suggesting that campanulates may be restricted to food-rich habitats. 3.) The daily ration required to maintain r m that is half the maximal population growth rate increased with increasing Asplanchna body mass and is described by the equation H=1.107 W1.103 where H=ration level and W=Asplanchna body mass. This population growth characteristic may reflect adaptations of rotifers to resource level. 4.) The relationships between ration level, food concentration, and Asplanchna body mass do not support the predictions of the size-efficiency hypothesis but are consistent with observed patterns of species distribution in nature.


Evaluation of a taste sensor instrument (electronic tongue) for use in formulation development.
A taste sensor instrument (electronic tongue) was evaluated to determine its utility in developing a taste-enhanced liquid formulation. To train the electronic tongue, human sensory panel data were collected for two prototype formulations, a solution of the drug in water and several marketed products. Studies using the electronic tongue were conducted to determine taste-masking effectiveness of formulations compared to a matching placebo, to establish correlation with human sensory data, and to evaluate unknown formulations and predict their bitterness scores. In the first experiment, the effectiveness of a proposed taste-masking strategy was determined by comparing formulation prototypes containing a bitter active pharmaceutical ingredient (API) against corresponding placebos (i.e. formulations without an active ingredient) using electronic tongue data. The analysis of the electronic tongue data was based on the assumption that the drug was well taste masked if the placebo matched the formulation with API. In a second set of experiments, electronic tongue data were compared to existing data from a human taste panel for several marketed products and prototype formulations. A good correlation (r(2)=0.99) was achieved from this comparison, and the relative taste of prototype formulations not tasted by humans was predicted.


The freshman year of college as a critical period for weight gain: an initial evaluation.
Prevention of obesity and weight maintenance have become important public health issues. One strategy for prevention of obesity is to identify critical periods of weight gain across the life span. The purpose of this initial evaluation was to determine whether the transition from high school to college is such a critical period. A total of 135 college students were weighed in September and December of their freshman year and a subset also provided data in May. Results showed that statistically significant but modest weight increases occurred during the freshman year for most participants. However, one quarter of participants gained at least 2.3 kg during the first semester of college, and the proportion of participants classified as overweight or obese increased markedly. For this subset of participants, the freshman year of college could be considered a critical period for weight gain. Identifying critical periods for weight gain may be an important first step towards the development of effective obesity prevention programs.


A study on voiding pattern of newborns with hypoxic ischemic encephalopathy.
To investigate the difference of voiding pattern between newborns with and those without hypoxic ischemic encephalopathy (HIE). Forty hospitalized newborns aged 4-21 days were included in this study. Twenty-one were preterm newborns with HIE, and the remaining 19 preterm newborns were without HIE. The voided volume, postvoid residual (PVR) volume, consciousness at voiding, voiding time, voiding frequency, and quantity of intake milk and liquid within 4 hours from 8 am-12 pm were recorded. The liquid intake was the same in both groups according to standard protocol. The diaper weight difference before and after voiding was defined as voided volume. The PVR volume was determined by ultrasound. The state of consciousness at voiding was monitored by electroencephalography. Voided volume and rate of consciousness at voiding was significant lower in newborns with HIE compared with the control group ([10.8 ± 6.5 mL, 16.3 ± 17.1%] vs [14.1 ± 7.1 mL, 57.1 ± 21.0%], P <.05, respectively), whereas PVR volume and voiding frequency were significant higher ([1.6 ± 1.0 mL, 4.0 ± 1.1 times] vs [1.2 ± 0.9 mL, 3.2 ± 0.9 times] per 4 hours, P <.05, respectively). The differences in voiding pattern supported the concept that the higher centers of the central nervous system were involved in the control of voiding. HIE had a significant effect on voiding pattern of preterm newborn.


The AdS5 × S5 superstring.
The duality between the type IIB superstring theory in an AdS5 × S5 background with N units of five-form flux and N = 4 super Yang-Mills theory with a U(N) gauge group has been studied extensively. My version of the construction of the superstring world-sheet action is reviewed here.


Parent Perspectives of Neonatal Intensive Care at the End-of-Life.
This descriptive qualitative study explored parent experiences related to their infant's neonatal intensive care unit (NICU) hospitalization, end-of-life care, and palliative care consultation. "Life and death in the NICU environment" emerged as the primary theme with the following categories: ups and downs of parenting in the NICU, decision-making challenges in the NICU, and parent support. Parents encountered challenges with areas for improvement for end-of-life and palliative care in the NICU. Further research is necessary to understand barriers with integrating palliative care and curative care in the NICU, and how NICU care affects bereavement and coping outcomes after infant death.


A comparative observational study of early versus delayed feeding after percutaneous endoscopic gastrostomy.
Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice for long-term enteral feeding. This prospective observational study was carried out to compare the safety of commencing feeding 3 h compared to 16-24 h after PEG tube placement. One hundred and ten patients with oropharyngeal malignancies who had consented for PEG were enrolled. Trial-specific consent and IRB approval were not obtained because at the time when this study was done, this was not mandatory for observational studies which involved standard procedures. Alternate patients were started on early feeding within 3 h (group I) or after overnight observation of 16 to 24 h (group II). Five hundred milliliters of Ringer's lactate was infused over 4 h initially, followed 2 h later by 200 mL of formula feed. The patients were advised to take bolus feeds of 200 mL every 2 h and oral feeds ad libitum from the next day. All patients were evaluated on days 1, 2, 7, and 30. There were 55 patients (47 males) in group I and 54 patients (38 males) in group II who were matched for age (mean age 46.1 and 46.1 years, respectively). Complications included PEG site infection (1), peristomal leak (3), and displacement of the PEG tube (1) in group I. PEG site infection was seen in five patients in group II. All the complications were managed conservatively on an ambulatory basis. Initiation of tube feeding 3 h after an uncomplicated PEG was safe, well tolerated, and helped to reduce the hospital stay.


Periodontal-Systemic Disease: A Study on Medical Practitioners' Knowledge and Practice.
Oral health is intricately linked with systemic health. However, the knowledge and practice levels of medical practitioners (MPs) about this concern are extremely variable. The current study, therefore, sought to assess the status of knowledge and practice of MPs concerning the link between periodontal disease and different systemic conditions as well as the efficacy of a webinar as an interventional tool in enhancing knowledge of MPs of Jazan Province of Saudi Arabia. This prospective interventional study involved 201 MPs. A 20-item questionnaire on evidence-based periodontal/systemic health associations was used. The participants answered the questionnaire before and 1 month after a webinar training that explained the mechanistic interrelation of periodontal and systemic health. McNemar test was performed for statistical analysis. Out of the 201 MPs who responded to the pre-webinar survey, 176 attended the webinar and hence were included in the final analyses. Sixty-eight (38.64%) were female, and 104 (58.09%) were older than 35 years. About 90% of MPs reported not being trained on oral health. Pre-webinar, 96 (54.55%), 63 (35.80%), and 17 (9.66%) MPs rated their knowledge about the association of periodontal disease with systemic diseases as limited, moderate, and good, respectively. Post-webinar, these figures improved remarkably: 36 (20.45%), 88 (50.00%), and 52 (29.55%) MPs rated their knowledge as limited, moderate, and good, respectively. Around 64% of MPs had relatively good levels of knowledge about the positive influence of periodontal disease treatment on diabetic patients' blood glucose levels. MPs revealed low levels of knowledge on the oral and systemic disease interrelationship. Conducting webinars on the oral-systemic health interrelationship seems to improve the overall knowledge and understanding of MPs.


β-Glucan receptors on IL-4 activated macrophages are required for hookworm larvae recognition and trapping.
Recent advances in the field of host immunity against parasitic nematodes have revealed the importance of macrophages in trapping tissue migratory larvae. Protective immune mechanisms against the rodent hookworm Nippostrongylus brasiliensis (Nb) are mediated, at least in part, by IL-4-activated macrophages that bind and trap larvae in the lung. However, it is still not clear how host macrophages recognize the parasite. An in vitro co-culture system of bone marrow-derived macrophages and Nb infective larvae was utilized to screen for the possible ligand-receptor pair involved in macrophage attack of larvae. Competitive binding assays revealed an important role for β-glucan recognition in the process. We further identified a role for CD11b and the non-classical pattern recognition receptor ephrin-A2 (EphA2), but not the highly expressed β-glucan dectin-1 receptor, in this process of recognition. This work raises the possibility that parasitic nematodes synthesize β-glucans and it identifies CD11b and ephrin-A2 as important pattern recognition receptors involved in the host recognition of these evolutionary old pathogens. To our knowledge, this is the first time that EphA2 has been implicated in immune responses to a helminth.


Application of artificial intelligence for automatic cataract staging based on anterior segment images: comparing automatic segmentation approaches to manual segmentation.
Cataract is one of the leading causes of blindness worldwide, accounting for >50% of cases of blindness in low- and middle-income countries. In this study, two artificial intelligence (AI) diagnosis platforms are proposed for cortical cataract staging to achieve a precise diagnosis. A total of 647 high quality anterior segment images, which included the four stages of cataracts, were collected into the dataset. They were divided randomly into a training set and a test set using a stratified random-allocation technique at a ratio of 8:2. Then, after automatic or manual segmentation of the lens area of the cataract, the deep transform-learning (DTL) features extraction, PCA dimensionality reduction, multi-features fusion, fusion features selection, and classification models establishment, the automatic and manual segmentation DTL platforms were developed. Finally, the accuracy, confusion matrix, and area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the two platforms. In the automatic segmentation DTL platform, the accuracy of the model in the training and test sets was 94.59 and 84.50%, respectively. In the manual segmentation DTL platform, the accuracy of the model in the training and test sets was 97.48 and 90.00%, respectively. In the test set, the micro and macro average AUCs of the two platforms reached >95% and the AUC for each classification was >90%. The results of a confusion matrix showed that all stages, except for mature, had a high recognition rate. Two AI diagnosis platforms were proposed for cortical cataract staging. The resulting automatic segmentation platform can stage cataracts more quickly, whereas the resulting manual segmentation platform can stage cataracts more accurately.


Putting the 'patient' back into patient-centred care: an education perspective.
Patient-centred care is a value espoused by most healthcare systems and a concept taught in nursing education programs as a fundamental concept of patient care. In this study, we focused on the patient's experience of patient-centredness, interviewing eighteen patients and eight family members about their experiences as patients on an in-patient acute care medical unit in a large hospital in Canada. Approximately half of the patients expressed satisfaction with their experiences and their involvement in decisions about their healthcare. The remainder expressed concerns about their care that jeopardized their experiences of patient-centredness. These areas concerned issues of communication with and among healthcare professionals, relationships with these care providers, trust and respect in the professional relationships, and general satisfaction with care. Participants provided advice to professional students about ways to interact more effectively with their patients to establish caring, empathetic, patient-centred relationships as the basis for care. We address patient recommendations to support learner understanding of the patient experience both in classrooms and clinical experiences throughout educational programs as a means to enhance their patient-centredness.


Modeling multi-mutation and drug resistance: analysis of some case studies.
Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. Different genetic alterations occur when tumor cells divide. Among new generations of tumor cells, some may express intrinsic resistance to a specific chemotherapeutic agent. Also, some tumor cells may carry a gene that can develop resistance induced by the therapeutic drug. The methods by which the therapeutic approaches need to be revised in the occurrence of drug induced resistance is still being explored. Previously, we introduced a model that expresses only intrinsic drug resistance in a conjoint normal-tumor cell setting. The focus of this work is to expand our previously reported model to include terms that can express both intrinsic drug resistance and drug-induced resistance. Additionally, we assess the response of the cell population as a function of time under different treatment strategies and discuss the outcomes. The model introduced is expressed in the format of coupled differential equations which describe the growth pattern of the cells. The dynamic of the cell populations is simulated under different treatment cases. All computational simulations were executed using Mathematica v7.0. The outcome of the simulations clearly demonstrates that while some therapeutic strategies can overcome or control the intrinsic drug resistance, they may not be effective, and are even to some extent damaging, if the administered drug creates resistance by itself. In the present study, the evolution of the cells in a conjoint setting, when the system expresses both intrinsic and induced resistance, is mathematically modeled. Followed by a set of computer simulations, the different growing patterns that can be created based on choices of therapy were examined. The model can still be improved by considering other factors including, but not limited to, the nature of the cancer growth, the level of toxicity that the body can tolerate, or the strength of the patient's immune system.


Differential modulatory effects of transcranial direct current stimulation on a facial expression go-no-go task in males and females.
The ability to recognize facial expressions has been shown to be different between males and females. Here we aimed to explore further this matter and investigate whether the effects of tDCS applied over the superior temporal cortex differs between males and females during a facial expression go-no-go task. Fourteen healthy subjects were exposed to a facial expression go-no-go task while they received two different conditions of stimulation: anodal tDCS of the left temporal cortex (with cathodal stimulation of the right temporal cortex) and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 5 min of stimulation), subjects underwent a go-no-go task. The results showed that women had significantly more correct answers when compared to men (p=0.03) that was independent of condition of stimulation and valence of figures. In addition, women made significantly less errors during temporal stimulation when compared to sham stimulation (p=0.009) when responding to sad faces. Similarly, men made significantly more errors during temporal active stimulation as compared with sham stimulation (p=0.004) when responding to sad faces. Our results confirmed the notion that performance to facial expression recognition is increased in females compared with males and that modulation of temporal cortex with tDCS leads to differential effects according to gender.


Dual pathogenicity island transfer by piggybacking lateral transduction.
Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during prophage induction. Here, we report that superantigen-carrying staphylococcal pathogenicity islands (SaPIs) employ a related but more versatile and complex mechanism of gene transfer to drive chromosomal hypermobility while self-transferring with additional virulence genes from the host. We found that after phage infection or prophage induction, activated SaPIs form concatamers in the bacterial chromosome by switching between parallel genomic tracks in replication bubbles. This dynamic life cycle enables SaPIbov1 to piggyback its LT of staphylococcal pathogenicity island vSaα, which encodes an array of genes involved in host-pathogen interactions, allowing both islands to be mobilized intact and transferred in a single infective particle. Our findings highlight previously unknown roles of pathogenicity islands in bacterial virulence and show that their evolutionary impact extends beyond the genes they carry.


Author Correction: Exploring the pathology of an epidermal disease affecting a circum-Antarctic sea star.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.
Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.


Subunit III of the chloroplast ATP-synthase can form a Ca(2+)-binding site on the lumenal side of the thylakoid membrane.
Subunit III, the 8 kDa component of the chloroplast CFo H+ channel, was isolated and purified from pea thylakoids for the purpose of studying its Ca(2+)-binding properties. After n-butanol extraction and ether precipitation, HPLC purification was accomplished using a poly(styrene-divinylbenzene) column which removes lipid and protein contaminations. The main components of protein contamination were two hydrophobic proteins of near 4 kDa molecular mass, the psaI and psbK gene products associated with PSI and PSII reaction centers, respectively. Purified subunit III as well as the unfractionated organic-solvent soluble preparation were used in a 45Ca(2+)-ligand blot assay known to detect high affinity Ca(2+)-binding sites in proteins. Polypeptides were separated with SDS-PAGE and were transferred onto PVDF membranes. Treatment of the membrane with 45CaCl2 in the presence of 10-fold excess of MgCl2 and 200-fold excess KCl led to the labeling of only the 8 kDa polypeptide. The Ca2+ binding was inhibited after derivatizing aqueously exposed carboxyl groups with a water soluble carbodiimide plus a nucleophile, after de-formylation of the N-terminal methionine, or with a subsequent treatment with La3+. Ca2+ binding was maximum at pH 7.5-8.5 and was greatly decreased at acidic pH. Dicyclohexylcarbodiimide treatment (no nucleophile was added) of thylakoid membranes, which derivatizes the hydrophobically located Glu-61, decreased the electrophoretical mobility of isolated subunit III but did not inhibit the Ca2+ binding. The data indicate that the carbonyl group of the formylated N-terminal Met-1 and probably the carboxyl group of the subunit III C-terminal Val-81 provide some of seven essential oxygen ligands normally required for defining a Ca(2+)-binding site in proteins. It is probable, but not yet established that an oligomeric form of subunit III polypeptides is essential for forming the Ca(2+)-binding site. Based on the accepted models for the hairpin conformation of the subunit III, it does seem clear that the Ca(2+)-binding site can form on the lumenal side of the membrane in the functional CFo structure.


P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhiitor Ensartinib in Cancer Cells.
Ensartinib (X-396) is a promising second-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK) that was developed for the treatment of ALK-positive non-small-cell lung cancer. Preclinical and clinical trial results for ensartinib showed superior efficacy and a favorable safety profile compared to the first-generation ALK inhibitors that have been approved by the U.S. Food and Drug Administration. Although the potential mechanisms of acquired resistance to ensartinib have not been reported, the inevitable emergence of resistance to ensartinib may limit its therapeutic application in cancer. In this work, we investigated the interaction of ensartinib with P-glycoprotein (P-gp) and ABCG2, two ATP-binding cassette (ABC) multidrug efflux transporters that are commonly associated with the development of multidrug resistance in cancer cells. Our results revealed that P-gp overexpression, but not expression of ABCG2, was associated with reduced cancer cell susceptibility to ensartinib. P-gp directly decreased the intracellular accumulation of ensartinib, and consequently reduced apoptosis and cytotoxicity induced by this drug. The cytotoxicity of ensartinib could be significantly reversed by treatment with the P-gp inhibitor tariquidar. In conclusion, we report that ensartinib is a substrate of P-gp, and provide evidence that this transporter plays a role in the development of ensartinib resistance. Further investigation is needed.


Current understanding of Th2 cell differentiation and function.
Helper T cell (Th) has been identified as a critical immune cell for regulating immune response since 1980s. The type 2 helper Tcell (Th2), characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, plays a critical role in immune response against helminths invading cutaneous or mucosal sites. It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea. Currently, most studies have shed light on Th2 cell function and behavior in specific diseases, such as asthma and helminthes inflammation, but not on Th2 cell itself and its differentiation. Based on different cytokines and specific behavior in recent research, Th2 cell is also regarded as new subtypes of T cell, such as IL-9 secreting T cell (Th9) and CXCR5(+) T follicular helper cells. Here, we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.


A hemodialysis patient with bone disease after pregnancy: a case report.
Pregnancy is rare in women on hemodialysis. Recommendations for the treatment of secondary hyperparathyroidism (sHPT) and preservation of bone health in pregnant dialysis patients are lacking. We present the case of a young woman with end-stage kidney disease (ESKD) due to lupus nephritis, who developed multiple brown tumors while on hemodialysis during her second pregnancy. During her first pregnancy sHPT was well controlled and no skeletal complications occurred. Before the second pregnancy she developed severe sHPT. During pregnancy, dialysis time was increased to 24 h per week, the patient was given oral calcitriol, and the dialysate calcium concentration was set at 1.5 mmol/l. In week 20 the patient complained about bone pain in her left hip. Magnetic resonance imaging revealed a cystic lesion compatible with a brown tumor. The baby was delivered in the 36th week by cesarean section. Further assessment identified multiple brown tumors of her skeleton, including the acetabulum, tibia, ribs, skull, thoracic spine and thumb. She required multiple orthopedic surgeries. Three months after pregnancy, etelcalcetide was started, which brought about a gradual improvement in her sHPT. This case demonstrates that the combination of pregnancy and severe sHPT in dialysis patients can have deleterious consequences for bone health.


Variable selection for discriminating herbal medicines with chromatographic fingerprints.
When discriminating herbal medicines with pattern recognition based on chromatographic fingerprints, typically, the majority of variables/data points contain no discrimination information. In this paper, chemometric approaches concerning forward selection and key set factor analysis using principal component analysis (PCA), unweighted and weighted methods based on the inner- and outer-variances, Fisher coefficient from the between- and within-class variations were investigated to extract representative variables. The number of variables retained was determined based on the cumulative variance percent of principal components, the ratio of observations to variables and the factor indicative function (IND). In order to assess the methods for variable selection and criteria levels to determine the number of variables retained, the original and reduced datasets were compared with Procrustes analysis and a weighted measure of similarity. Moreover, the tri-variate plots of the first three PCA scores were used to visually examine the reduced datasets in low dimensional space. Herbal samples were finally discriminated by use of Bayes discrimination analysis with the reduced subsets. The case study for 79 herbal samples showed that, the methods of forward selection associating the variables with the loadings closest to 0 and key set factor analysis were preferable to determine the representative variables. Procrustes analysis and the weighted measure were not indicative to extract representative variables. High matching between the original and reduced datasets did not suggest high prediction accuracy. Visually examining the PC1-PC2-PC3 scores projection plots with the reduced subsets, not all the herb samples could be separated due to the complexity of chromatographic fingerprints.


The impact of COVID-19 pandemic on anxiety and depression among physical therapists in Saudi Arabia: a cross-sectional study.
A physical therapist may become infected while treating a patient since they are in direct contact with them or within a two-meter radius. In addition, physical therapists may feel that they are more susceptible to COVID-19 infection when applying rehabilitation practices, which often involve direct contact with patients. The physical therapist were surveyed on their level of anxiety and depression due to the Coronavirus disease pandemic (COVID-19). The physical therapists were asked to complete two reliable and validated scales, the Generalized Anxiety Disorder scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), to identify the presence of anxiety and depression in the participants. In addition, logistic regression models were used to determine the general characteristics of anxiety or depression. Among the 117 physical therapists who completed and participated in the study, 74 (63%) and 65 (55.5%) physical therapists reported having symptoms of anxiety and depression, respectively. The prevalence of overall anxiety levels was higher; mild (OR = 2.09; P = 0.08), moderate (OR = 2.26; P = 0.15), and severe levels six times as high (OR = 6.28; P = 0.1) in females compared to male physical therapists. Females, younger age, unmarried individuals, not having children, and not living with family showed a higher prevalence of anxiety and depression. Binary logistic regression analysis also revealed that the female gender, a single individual, and having no children were associated with anxiety and depression. A significant percentage of physical therapists reported symptoms of anxiety and depression, especially among females, younger age, single individuals, not having children, and not living with family. Thus, the mental health of physical therapists is suggested to be constantly and cautiously monitored, especially for those at high risk of developing psychological symptoms.


Effect of a Multimedia Educational Tool on Contraception Use 1 Year Postpartum.
Supported in part by a research grant from Investigator-Initiated Studies program of Organon. The opinions expressed in this paper are those of the authors and do not necessarily represent Organon. ClinicalTrials.gov , NCT04291040.


Factors affecting recurrence and metastasis in conjunctival melanoma.
To evaluate clinical and demographic characteristics and factors affecting recurrence, metastasis, and survival in conjunctival melanoma (CM). The clinical records of 45 patients who were treated for CM between October 1998 and June 2022 were retrospectively evaluated. Age, gender, presence of underlying conjunctival nevus-primary acquired melanosis (PAM), tumor stage according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, tumor basal diameter, tumor thickness, lymph node (LN) involvement, metastasis, presence of tumor at the surgical margin, treatment method, need for adjuvant therapy, local tumor control, recurrence, and survival were recorded. Twenty-one (46.7%) patients were female and 24 (53.3%) patients were male. The mean age at diagnosis was 53.2 ± 16.1 years. Median follow up time was 12 (1-300) months. Fifteen (33.3%) patients had conjunctival PAM; 2 (4.4%) patients had conjunctival nevus. The tumor stage was T1 in 24 (55.8%), T2 in 13 (30.2%), and T3 in 6 (14.0%) of the cases. The T stage in 2 cases could not be determined. For stage T1 and T2 CM, in addition to excisional biopsy (EB) and cryotherapy, alcohol epitheliectomy (AE) was performed in 17 cases (37.8%), superficial sclerectomy (SS) was performed in 7 (15.6%), and amnion membrane transplantation (AMT) due to a large conjunctival defect in 9 (20.0%). Six (14.0%) T3 cases underwent primary exenteration. Positive surgical margins were observed in 23 (51.1%) of the excised tumors at histopathologic examination. Adjuvant topical mitomycin-C (MMC) was used in 7 (30.4%) and strontium-90 episcleral brachytherapy in 4 (17.4%) of the 23 cases with tumor-positive borders. During the follow-up, recurrence was seen in 14 (31.1%) cases. According to Kaplan Meier analysis, the mean time to recurrence development was 90.5 ± 16.1 months and the 5-year recurrence free rate was 52.0%. Fourteen of the recurrent cases underwent EB + cryotherapy, 3 underwent AE + SS, and 3 underwent secondary exenteration. Metastasis and LN involvement occurred in 11 (24.4%) and 8 (17.8%) of the cases, respectively. Four (8.9%) cases expired during follow-up. According to Kaplan-Meier analysis, the mean time to metastasis was 106.2 ± 17.3 months and the 5-year metastasis free rate was 52.0%. While recurrence was more frequent in CM developing from PAM/nevus, metastasis was more frequent in men and those with LN involvement. Conjunctival melanoma was a malignant tumor with high recurrence and metastasis rates. Precursor nevus/PAM is a risk factor for recurrence, while male gender and regional LN involvement were risk factors for metastasis in this study.


Molecularly imprinted quartz crystal microbalance sensor based on poly(o-aminothiophenol) membrane and Au nanoparticles for ractopamine determination.
A molecularly imprinted quartz crystal microbalance (QCM) sensor for ractopamine (RAC) detection was developed by electrodepositing a poly-o-aminothiophenol membrane on an Au electrode surface modified by self-assembled Au nanoparticles (AuNPs). The modified electrodes were characterized by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. This molecularly imprinted QCM sensor showed good frequency response in RAC binding measurements and the introduction of AuNPs demonstrated performance improvements. Frequency shifts were found to be proportional to concentration of RAC in the range of 2.5×10(-6) to 1.5×10(-4) mol L(-1) with a detection limit of 1.17×10(-6) mol L(-1) (S/N=3). The sensor showed a good selective affinity for RAC (selectivity coefficient >3) compared with similar molecules and good reproducibility and long-term stability. This research has combined the advantages of high specific surface area of AuNPs, high selectivity from molecularly imprinted electrodeposited membrane and high sensitivity from quartz crystal microgravimetry. In addition, the modified electrode sensor was successfully applied to determine RAC residues in spiked swine feed samples with satisfactory recoveries ranging from 87.7 to 95.2%.


Synthesis of beta-D-arabinofuranosyl-1-monophosphoryl polyprenols: examination of their function as mycobacterial arabinosyl transferase donors.
A convenient synthetic strategy has been developed to produce libraries of beta-D-arabinofuranosyl-monophosphorylpolyprenol. Those containing C50 and C55 polyprenols were the most active as donors for the cell-free synthesis of the arabinans of mycobacterial cell walls.


Intermediate distributions and primary yields of phenolic products in nitrobenzene degradation by Fenton's reagent.
Nitrobenzene thermal degradation was investigated using the Fenton reagent in different experimental conditions. Reaction products were analyzed by HPLC, GC-MS, LC-MS and IC. The products obtained at different nitrobenzene conversion degrees show that degradation mainly involves successive hydroxylation steps of the aromatic ring and its subsequent opening followed by oxidation of corresponding aliphatic compounds. Our results show as primary reaction products: 4-nitrophenol, 3-nitrophenol, 2-nitrophenol, phenol and 1,3-dinitrobenzene, indicating that both hydroxylation and nitration reactions are involved. The formation of phenolic products can be explained by postulating an initial step of HO() addition to nitrobenzene ring. The mechanisms of primary reaction pathways are discussed and a detailed kinetic analysis to obtain the true primary yields of phenolic products is proposed. The relative yields observed for nitrophenol isomers do not follow the expected orientation according to deactivating characteristics of the nitro group but significantly depend on Fe(+2), Fe(+3), H(2)O(2) and O(2) concentrations. The understanding of the effect of reaction conditions on the relative product distribution benefits the application of Fenton and Fenton-like systems to waste water treatment.


Effects of training and weight support on muscle activation in Parkinson's disease.
The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients.


Structure and Function of Multidrug Resistance Protein 1.
This review considers one of the most clinically relevant representatives of the ABC transporters - multidrug resistance protein 1 (P-glycoprotein 1 or Pgp). Data on the primary, secondary, and tertiary structure of the protein, its synthesis and degradation, and roles of its fragments in transporter activity are presented. Particular attention is given to the mechanism of functioning of Pgp. In view of the absence of a generally recognized mechanism of action of Pgp, several existing models of the protein transport cycle are discussed. Epigenetic regulation of the ABCB1 gene and modulation of Pgp expression by microRNAs are discussed.


CSF Gusher in Cochlear Implant Surgery-does it affect surgical outcomes?
The purpose of this prospective study was to measure surgical outcomes in cases of cerebrospinal fluid gusher in cochlear implant surgery. Demographic, radiological, neurophysiological and surgical results were evaluated in nine cases of patients with cerebrospinal fluid gusher during cochlear implant surgery, out of 164 unilateral cochlear implant procedures. Review of literature and our management technique is discussed. Nine cases had cerebrospinal fluid leak during surgery. Out of three cases of incomplete partition type II, two had cerebrospinal fluid gusher while one had milder ooze. Two cases with large vestibular aqueduct syndrome had intraoperative cerebrospinal fluid gusher. Four cases of gusher had no predictable risk factors on clinical history, examination or preoperative radiology. All cases were managed with meticulous packing of round window site without any other additional measures such as lumbar drain or use of tissue glue. These cases showed no symptoms or signs of cerebrospinal fluid leak in the follow-up period. We recommend careful meticulous packing of the round window around the electrode using periosteum until cerebrospinal fluid leak is controlled in all cases of cerebrospinal fluid gushers. We also recommend a very conservative approach to managing these patients in the immediate postoperative period.


Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning Using Speckle Tracking Echocardiography.
Carbon monoxide (CO) poisoning could cause significant cardiac injury. This study aimed to evaluate patients with CO poisoning by using speckle tracking echocardiography (STE), a potentially more sensitive technique, to identify left systolic ventricular dysfunction for the first time in the literature. Seventy-two patients who were exposed to CO poisoning were studied. Blood collection and echocardiography were performed at admission and after patients' discharge on days 10-15 (mean 12 days). Global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated using STE. In order to find the normal strain levels and to compare it to the patient with CO poisoning, 35 healthy subjects were included in the study. Left ventricular ejection fraction was analyzed according to Simpson's method. Patients were divided into two groups based on their LVEF values. LVEF < 55%, Group 1 (n = 24); LVEF ≥ 55%, Group 2 (n = 48). The reduction in Group 1 strain levels decreased in correlation with LVEF (p < 0.001) while in Group 2, there were no significant changes in LVEF but strain levels were significantly reduced (p = 0.091; p < 0.001). Compared with the control group patients, admission GLS and GLC values of CO-poisoned patients were significantly low both in Group 1 and 2. On the contrary, no significant difference was observed when compared with follow-up GLS value. For prediction of CO cardiotoxicity, the cutoff value of GLS was ≥ - 19.1 with a sensitivity of 70.3% and a specificity of 100% [(AUC) 0.840, 95% (CI) 0.735-0.916; p < 0.001] in the ROC curve analyses. GLS was found as independent predictors of cardiotoxicity. Our study demonstrates the potential of using systolic strain values obtained using 2D-STE in determining cardiotoxicity due to CO poisoning. Speckle tracking echocardiography has the potential of demonstrating subtle LV systolic dysfunction even in CO poisoning patients with preserved EF.


Next generation synthetic memory via intercepting recombinase function.
Here we present a technology to facilitate synthetic memory in a living system via repurposing Transcriptional Programming (i.e., our decision-making technology) parts, to regulate (intercept) recombinase function post-translation. We show that interception synthetic memory can facilitate programmable loss-of-function via site-specific deletion, programmable gain-of-function by way of site-specific inversion, and synthetic memory operations with nested Boolean logical operations. We can expand interception synthetic memory capacity more than 5-fold for a single recombinase, with reconfiguration specificity for multiple sites in parallel. Interception synthetic memory is ~10-times faster than previous generations of recombinase-based memory. We posit that the faster recombination speed of our next-generation memory technology is due to the post-translational regulation of recombinase function. This iteration of synthetic memory is complementary to decision-making via Transcriptional Programming - thus can be used to develop intelligent synthetic biological systems for myriad applications.


Awareness and use of a cognitive aid for anesthesiology.
The Veterans Health Administration's (VHA's) National Center for Patient Safety developed a cognitive aid to help anesthesiologists manage rare, high-mortality adverse events. Six months after the aids were sent to VHA facilities with anesthesia machines, anesthesia providers were surveyed about their knowledge and use of the aid. Seven percent of respondents had used the cognitive aid in an emergency ("emergent users"). Most (87%) of respondents were aware of the aid. Half used it only as a reference ("reference users"), 30% were nonusers, and 13% of respondents were unaware of the aid. User groups did not differ regarding exposure to emergencies. All emergent users reported that it helped during an emergency, and 93% reported that it was well designed and easy to use. Emergent users were more likely than other groups to have first found out about it through formal orientation (53%; p < .001). Nonusers (46%) and reference users (38%) were more likely than emergent users (30%) and those who never saw it (5%) to have first found out about it through informal communication with a colleague (p = < 0.001). The majority of those who never saw the aid first became aware of it through this survey (71%; p < .001). The aid was used most commonly for difficult airway. A cognitive aid for use in rare emergencies proved clinically useful to anesthesia providers.


The universal stress protein A of Escherichia coli is required for resistance to DNA damaging agents and is regulated by a RecA/FtsK-dependent regulatory pathway.
The link between cell division defects and the induction of the universal stress response is demonstrated to operate via the RecA regulator of the SOS response. An insertion in the cell division gene ftsK upregulates uspA in a recA-dependent manner. Unlike true SOS response genes, this upregulation only occurs in growth-arrested cells and is LexA independent. Thus, besides ppGpp-dependent starvation signals, DNA aberrations transduce RecA-dependent signals to the uspA promoter, which only affect the promoter during stasis. Further, we show that ftsK itself, like uspA, is induced in stationary phase and that this induction requires the stringent control modulon rather than activated RecA. Thus, ftsK, like uspA, is regulated by at least two global regulators: ppGpp of the stringent control network and RecA of the SOS modulon. We suggest that UspA is a new bona fide member of the RecA-dependent DNA protection and repair system, as mutants lacking functional UspA were found to be sensitive to UV irradiation and mitomycin C exposure. Moreover, the UV sensitivity of uspA mutants is enhanced in an additive manner by the ftsK1 mutation.


Testing the directed dispersal hypothesis: are native ant mounds (Formica sp.) favorable microhabitats for an invasive plant?
Ant-mediated seed dispersal may be a form of directed dispersal if collected seeds are placed in a favorable microhabitat (e.g., in or near an ant nest) that increases plant establishment, growth, and/or reproduction relative to random locations. We investigated whether the native ant community interacts with invasive leafy spurge (Euphorbia esula) in a manner consistent with predictions of the directed dispersal hypothesis. Resident ants quickly located and dispersed 60% of experimentally offered E. esula seeds. Additionally, 40% of seeds whose final deposition site was observed were either brought inside or placed on top of an ant nest. Seed removal was 100% when seeds were placed experimentally on foraging trails of mound-building Formica obscuripes, although the deposition site of these seeds is unknown. Natural density and above-ground biomass of E. esula were greater on Formica mound edges compared to random locations. However, seedling recruitment and establishment from experimentally planted E. esula seeds was not greater on mound edges than random locations 3 m from the mound. Soil from Formica mound edges was greater in available nitrogen and available phosphorus relative to random soil locations 3 m from the mound. These results suggest Formica ant mounds are favorable microhabitats for E. esula growth following seedling establishment, a likely consequence of nutrient limitation during plant growth. The results also indicate positive species interactions may play an important role in biological invasions.


A new analytical method for selective pre-concentration of free silver in estuarine waters using liquid membranes.
Silver is recognized as an important pollutant of natural waters. This element is a selective tracer of anthropogenic pollution related to sewage. Studying its bio-availability requires the application of specific separation of the free ion. A liquid membrane is proposed for separating Ag(+) from estuarine water samples. A bulk liquid membrane (BLM) has been selected. Free silver is transported from the sample to a receiving solution through an organic membrane containing tri-isobutylphosphine sulfide (TIBPS). Effects of formation of chlorinated and organic complexes on silver pertraction have been evaluated. The extent of formation of the aforementioned complexes has been based on the decrease of silver transport to the receiving phase, measured as enrichment factor (EF), because only Ag(+) is assumed to be transported. Finally, after quantifying the effects of the employed ligands on EF, total concentration of silver can be estimated from the experimental data of Ag(+) analyzed by the proposed BLM system.


Global exponential stability of neural networks with time-varying delay based on free-matrix-based integral inequality.
This paper is concerned with global exponential stability problem for a class of neural networks with time-varying delays. Using a new proposed inequality called free-matrix-based integral inequality, a less conservative criterion is proposed, which is expressed by linear matrix inequalities. Two numerical examples are given to show the effectiveness and superiority of the obtained criterion.


Use of molecular methods to characterize the bacterial community and to monitor different native starter cultures throughout the ripening of Galician chorizo.
The development of Lactobacillus and Staphylococcus strains used as starter cultures throughout the ripening of Galician chorizo, a traditional dry fermented sausage from the north-west of Spain, was monitored combining different molecular-based techniques. The bacterial diversity occurring in the inoculated sausages at the beginning and the end of the ripening was also studied and compared to the indigenous population in an uninoculated control batch. Real-time PCR was used to monitor the Lactobacillus and Staphylococcus community using genus and species-specific primer to quantify the occurring microbiota. The identification of isolates at genus or species level was achieved by specific PCR and 16S rRNA gene sequencing. rep-PCR using (GTG)5-PCR primer was used to characterize this bacterial community at strain level. According to the data obtained, the strains Lactobacillus sakei LS131, Staphylococcus equorum SA25 and Staphylococcus saprophyticus SB12 were dominant during the ripening process, whereas the strain Staphylococcus epidermidis SA49, that was added in order to study its behaviour with a merely scientific purpose, did not succeed in dominating ripening, since it seemed to be outcompeted by autochthonous microbiota. In conclusion, the combination of a quantitative method such as real-time PCR with the identification and typing techniques used in this study (genus and species-specific PCR, 16S rRNA gene sequencing and (GTG)5-PCR) provided accurate and complete information about the starter cultures development, assessing their growth and survival over the ripening process.


Persistence of oral polio vaccine virus after its removal from the immunisation schedule in New Zealand.
On Feb 1, 2002, inactivated poliomyelitis vaccines replaced live-attenuated oral poliovirus vaccine (OPV) in New Zealand's immunisation schedule, allowing systematic monitoring of OPV virus circulation. Findings of paediatric-inpatient surveillance indicate that 7% of children excreted polioviruses before this switch, but none did so 1 month afterwards. Acute flaccid paralysis surveillance detected no poliovirus during and after the switch, whereas enterovirus surveillance detected poliovirus only once during the switch. Environmental surveillance identified polioviruses in sewage samples until May, 2002, after which they were detected infrequently. Intratypic differentiation and sequencing showed that all polioviruses were Sabin-like. Multiple surveillance methods hence showed that OPV strains did not persist for extended periods after a vaccine switch in a developed country with a temperate climate. Sequence homology with Sabin vaccine parent strains indicated that polioviruses detected more than 4 months after the switch were of recent origin, consistent with importation from OPV-using countries.


Dropout intentions in secondary education: Student temperament and achievement motivation as antecedents.
As early school leaving and dropping out from education pose a challenge for later life adjustment, it is important to identify antecedent factors for the risk of school dropout to tailor individual support for adolescents. Consequently, this study examines the role of adolescents' motivational beliefs and behaviors (i.e., success expectations, planning, and task-avoidance) as well as their temperament (i.e., extraversion/surgency, negative affectivity, effortful control, and affiliativeness) in their dropout intentions in the first year of upper secondary education. Participants were Finnish adolescents' (n = 536; 57% girls, mean age 12.39 at outset, standard deviation = 0.35) and their motivational beliefs and behaviors were measured in Grades 6 and 9. Their temperament was also measured in Grade 9. As for dropout intentions, they were measured in upper secondary education. The effects of gender, academic achievement, task value, and educational track were controlled for in the analyses. The results of latent growth modeling showed that, of motivational beliefs and behaviors, high success expectations and low task avoidance independently predicted lower dropout intentions. Success expectations in Grade 6 also mediated the effects of extraversion/surgency, negative affectivity and effortful control on subsequent school dropout intentions, whereas an increase in task avoidance in lower secondary school was a mediator between extraversion/surgency and dropout intentions. Our study provides novel understanding about how temperament is linked with motivational beliefs and behaviors and what roles they together play in subsequent school dropout intentions. Supporting students with different temperaments and achievement motivations would be important to prevent adverse consequences for both the individual and society.


Use of an Aortic Valve Replacement Simulation Model to Understand Hospital Costs and Resource Utilization Associated With Rapid-deployment Valves.
Aortic stenosis (AS) is the most common cause of adult valvular heart disease. In the past decade, minimally invasive surgery (MIS) to treat AS has gained popularity, especially if performed in combination with rapid deployment valves (RDVs), which shorten cross-clamp time (XCT). This study examines specific outcomes and related costs of aortic valve replacement (AVR) before and after the introduction of RDVs. We used the AVR simulator, an economic model developed to correlate cost and resource utilization associated with the adoption of RDVs, to compare 2 scenarios: (1) a current scenario based on standard AVR practices and (2) a proposed scenario based on increasing use of RDVs and an MIS approach. Both scenarios involved 3 subgroups of patients treated with (1) conventional AVR, (2) MIS, and (3) AVR combined with a coronary artery bypass graft. The current scenario (status quo) involved patients treated with traditional biological valves, and the proposed scenario involved patients who underwent implantation with an RDV. The AVR simulator was fed with real-world input data to estimate complication rates and resource consumption in the proposed scenario. Real-world input data for this analysis were obtained from patients diagnosed with a symptomatic heart valve disease between 2015 and 2018, at Clinica-San-Gaudenzio, Novara, Italy. Lastly, the AVR simulator estimated hospital savings by comparing the 2 scenarios. A total of 132 patients underwent implantation with a traditional biological valve, and 107 were treated with a commercial valve system. The RDV was associated with an increase of 52% of patients undergoing MIS, which generated a 6.1-h reduction of XCT and a total savings of €6695. RDVs also reduced intensive care unit (ICU) and hospital ward length of stay (LOS), leading to savings of €677 and €595 per patient, respectively. Mortality and blood transfusions also improved. The savings for the hospital (related to shorter XCT, hospital ward LOS, and ICU LOS) amounted to €144.111. Our findings were consistent with data gathered from our real-word setting, and results of a sensitivity analysis indicate that our findings were robust across different possible situations. Switching to RDVs and MIS procedures for AVRs was associated with a reduction of costs related to XCT, hospital ward LOS, and ICU LOS. Hospitals can upload literature- and experience-based clinical and cost values to the AVR simulator to estimate a hospital's performance with the introduction of RDVs compared with standard biological valves. This study was not randomized, so more extensive studies could confirm our results in the future.


The use of combined intravenous pulse methylprednisolone and oral cyclosporin A in the treatment of corneal graft rejection: a preliminary study.
Oral cyclosporin A used in addition to high-dose intravenous pulse methylprednisolone has been shown to have an adjunctive effect in reversing the rejection of liver and renal transplants. The aim of this prospective study was to evaluate the benefits and risks of this combined drug therapy in acute corneal graft rejection. Eleven patients with acute corneal graft rejection received the combined regimen of a single pulse of intravenous methylprednisolone (500 mg) and a low dose of oral cyclosporin A (to maintain a trough blood level of 100-200 micrograms/l). At a mean follow-up of 16.5 months (range 8-22 months) from the presentation of the graft rejection, reversal of graft rejection was achieved in 10 of 11 cases (90.9%). No recurrence of graft rejection was encountered during the study period. One patient developed a duodenal ulcer, which healed after medical treatment. No other complications were encountered. The high efficacy and low risk of the combined regimen demonstrated in this preliminary study call for a larger-scale prospective double-masked study to confirm the value of this treatment protocol.


MED1: an intelligent computer program for thoracic pain diagnosis.
MED1 is a fully implemented, medical expert system providing assistance in the diagnosis of patients complaining of chest pain. Its reasoning strategy combines efficient mechanisms for hypothesis generation and hypothesis evaluation in a model simulalting the basic features of the hypothesize-and-test approach found to be applied by diagnosing physicians. The knowledge acquisition facility of the program is comfortable enough to allow the expert physician to alter the knowledge base without understanding the basic code (LISP) of the program.


A higher dose of PEGylated gold nanoparticles reduces the accelerated blood clearance phenomenon effect and induces spleen B lymphocytes in albino mice.
Polyethylene glycol (PEG) is a multifunctional polymer that has many uses in medical and biological applications. Recently, PEG has been mainly used in developing nanomaterial-based drug delivery systems (DDS). PEG is characterized by its high solubility, biological inertness, and ability to escape from immune cells (stealthiness) after systemic injection. The most challenging problem for PEGylated nanomaterials is their rapid elimination from the bloodstream after repeated doses of systemic injection, called accelerated blood clearance (ABC). Therefore, in this study, the effect of PEGylated nanomaterial dose concentration on ABC induction will be investigated using quantitative, histological, and immunohistochemical analyses. A higher dose concentration (2 mg/kg) of PEGylated gold nanoparticles (PEG-coated AuNPs) reduced the ABC phenomenon when intravenously injected into mice preinjected with the same dose. In contrast, a lower dose concentration (< 1 mg/kg) significantly induced the ABC phenomenon by the rapid elimination of the second dose of PEG-coated AuNPs from the bloodstream. To explain the relationship between the dose concentration (from PEG and AuNPs) and the induction of ABC, the biodistribution of PEG-coated AuNPs in liver and spleen [reticuloendothelial systems (RES)-rich organs] was investigated. The injected dose of PEG-coated AuNPs accumulated mainly in the hepatic Kupffer cells and hepatocytes. Similarly, spleen red pulp received a higher amount of the injected dose of PEG-coated AuNPs. However, the biodistriution profiles of PEG-coated AuNPs after the first and second dose for different dose concentrations varied in RES-rich organs. Additionally, the number of B lymphocytes, which have an important role in producing anti-PEG immunoglobulin (Ig)M, was affected by the repeated dose of PEG-coated AuNPs in the spleen. Therefore, for effective nanomaterial-based DDS development, dose optimization of PEG molecules that express PEGylated nanomaterials is important to reduce the ABC phenomenon effect. The ideal concentration of PEG molecules used to coat nanomaterials and the role of RES-rich organs must be determined to control the ABC phenomenon effect of PEGylated nanomaterials.


Renal loss following extracorporeal shock wave lithotripsy.
A patient with life-threatening retroperitoneal hemorrhage after extracorporeal shock wave lithotripsy is presented. Despite angioinfarction of the involved renal unit, nephrectomy ultimately was required to control bleeding. The urological and hematological aspects of the management are discussed.


Spectrophotometric determination of lymphocyte mediated sheep red blood cell hemolysis in vitro.
An assay has been developed in which the degree of in vitro spleen cell-mediated sheep red blood cell (SRBC) hemolysis is quantitated spectrophotometrically (QHS). Immune mouse spleen cells, SRBC and guinea pig complement were incubated at 37 degrees C for 1 h in buffer, centrifuged, and the supernatant solutions read at 413 nm. The greatest degree of cell-mediated SRBC hemolysis was observed in day +5 harvested spleens following a day 0, 5% SRBC i.p. injection. In the assay system, it was found that a stimulator SRBC dose of 0.2% resulted in maximal stimulation with little non-specific hemolysis. This assay is presented as an alternative to the well established plaque forming and rosette assays.


The Effect of Pregnancy in the Hemoglobin Concentration of Pregnant Women: A Longitudinal Study.
The objective of this study was to estimate and identify the determinants of hemoglobin concentration before pregnancy, during pregnancy, and after labor and delivery. A prospective cohort study design was implemented. Data were collected from May 2015 to September 2018. A simple random sampling technique was used to select the participants. An interview technique was used to collect the data. Blood samples were collected before pregnancy, during each trimester, during labor and delivery, after third stage of labor, and at the 6-week postpartum period. Descriptive statistics were used to describe the profile of study participants. Generalized estimating equations were used to identify the determinants of hemoglobin concentration during each phase of pregnancy. The mean hemoglobin concentrations of primigravida and multigravida before pregnancy were 12.41 g/dl and 10.78 g/dl, respectively. The hemoglobin concentration decreases with consecutive trimester reaching the lowest level at 42 days after delivery. The hemoglobin concentrations of pregnant women were decreased by hookworm 0.24 g/dl [95% CI:0.18-0.29], multiple pregnancy 0.16 g/dl [95% CI: 0.07-0.24], episiotomy 0.05 g/dl [95% CI: 0.01-0.09], gravidity 0.15 g/dl [95% CI: 0.09-0.21], age 0.03 g/dl [95% CI: 0.03-0.04], and gestational age 0.1 g/dl [95% CI: 0.09-0.11]. The hemoglobin concentration increased by iron supplementation 1.02 g/dl [95% CI: 0.97-1.07] and birth weight 0.14 g/dl [95% CI: 0.02-0.11]. Pregnancy significantly decreases the hemoglobin concentration of pregnant women reaching the lowest point during labor and delivery. Recommendation. Regular anemia screening intervention should be implemented after delivery.


[Postoperative peritonitis (author's transl)].
Postoperative peritonitis is still one of the most common complications following abdominal surgery. The main reason is leakage of an anastomotic suture line. The diagnosis can be masked by a delayed appearance, by veiling of otherwise typical symptoms, or by misjudging minor symptoms. Therefore, the critical evaluation of sometimes minimal intestinal disorders or small changes in heart and respiratory rate seem to be very important. Only early relaparotomy yields satisfactory results. The aims of an operation for peritonitis should be definitive rather than palliative. The cause of peritonitis has to be corrected surgically to manage this severe clinical picture successfully.


Adrenergic lipolysis in human adipose tissue in vitro.
In human adipose tissue in vitro, dose-response curves of lipolytic agents in releasing free fatty acids and glycerol into an albumine-containing medium were followed. Norepinephrine and adrenaline produced about 20% of the maximal effect of isoproterenol, isopropylnorsynephrine about 40%, theophylline more than 100%. Found pD2 values were approximately 7.4 for isoproterenol and norepinephrine, approximately 5.9 for isopropylnorsynephrine. Phentolamine (1 times 10-5 M) elevated the maximal norepinephrine effects up to the isoproterenol maxima. Phenoxybenzamine (1 times 10-5 M) had significantly lower potentiating effects. Phenylephrine depressed lipolytic actions of isoproterenol (1 times 10-6 M) showing the same pI2 value 3.0 as well in human as in rat adipose tissue and exerted per se weak lipolytic effects also. It is concluded neither potentiating actions of alpha-blockers nor depressing effects of phenylephrine in human adipose tissue seem related to affecting adrenergic alpha-receptors. The existence of antilipolytic actions of adrenergic alpha-receptors is questioned.


Recurrent bacterial translocation from gut and sepsis in Head and neck cancer patients and its prevention by probiotics.
Head and neck cancers are the 6th most common cancer type in human malignant tumors and treated with chemoradiotherapy and surgery. Chemotherapy during these treatment modalities leads to damage of intestinal epithelial barriers and results in translocation of intestinal bacteria in bloodstream through invasion in these damaged regions. In this report, we report two cases of hypopharyngeal cancer patients, both of whom received chemotherapy before surgery. The patients demonstrated repeated sepsis before and after surgery, supporting translocation of intestinal bacteria. Proper continuous probiotic use prevented proliferation and intestinal bacterial translocation. Hypothesis of bacterial translocation and prevention by probiotics are discussed.


Monoterpene cyclases: physicochemical features required for pyrophosphate binding determined from inhibition by structural analogs.
Monoterpene cyclases catalyze the divalent metal ion-dependent conversion of geranyl pyrophosphate, the ubiquitous C10 intermediate of isoprenoid biosynthesis, to a variety of monoterpene skeletons, and the pyrophosphoryl moiety is a primary determinant for substrate binding by these enzymes. To determine what specific features of this functional group are critical for enzymatic recognition, inorganic pyrophosphate and a series of structurally related analogs were examined as inhibitors of geranyl pyrophosphate:(+)-alpha-pinene cyclase and geranyl pyrophosphate:(+)-bornyl pyrophosphate cyclase from sage (Salvia officinalis). Analysis of trends in the magnitude of inhibition by the analogs relative to inorganic pyrophosphate indicated that the combination of ionization state (formal charge) at the enzymatic pH optimum, ability to chelate divalent metal ions, and intramolecular flexibility is required for effective interaction with both cyclases. Only when all of these criteria are met is inhibition of cyclization comparable to that observed with inorganic pyrophosphate.


The bookmark method to establish minimum performance standards for intensive care flight paramedics performing helicopter winch rescue.
We aimed to use the bookmark method to establish minimum standards for selecting intensive care flight paramedics. Two subject matter expert (SME) focus groups reviewed nine videos of decreasing duration showing land and water helicopter rescue tasks. Focus Group 1 (FG1, n = 10) viewed videos individually off-site, whilst Focus Group 2 (FG2, n = 9) attended a face-to-face session. All SMEs selected the video they judged as the appropriate pace for the task then reviewed feedback. For both groups, the process was repeated until 80% agreement was achieved, or three rounds were completed (whichever occurred first). FG1 and FG2 achieved agreement after two rounds for the land task. For the water task, FG1 did not reach agreement. FG2 reached consensus after two rounds. The selected task durations were similar. The bookmark method is valuable to determine performance standards for performing winch rescue, and SMEs are more likely to reach consensus when face-to-face.


Potent γ-amino butyric acid producing psychobiotic Lactococcus lactis LP-68 from non-rhizospheric soil of Syzygium cumini (Black plum).
Gamma amino butyric acid (GABA) is a chemical messenger that plays a significant role in muscle relaxation and brain health. Certain lactic acid bacteria (LAB) produce significant levels of GABA and thus act as potential psychobiotic cultures. In the present study, LAB were isolated from non-rhizospheric soil sample of Syzygium cumini (Black plum). A total of 57 LAB were isolated on the basis of their morphological and acid producing characteristic on de Man Rogosa Sharpe (MRS) agar. Only seven isolates were found to produce GABA (0.09-1.13 gL-1) in MRS broth and were identified as Lactococcus. However, L. lactis LP-68 produced highest amount of GABA and was selected for further optimization of culture conditions (pH, temperature and MSG) by response surface methodology (RSM). The optimization resulted in approximately four-fold increase in GABA production (4.11 gL-1). The results indicate that the L. lactis LP-68 can be used as starter culture for production of GABA-enriched functional foods.


Synthesis of phosphatidly-dCMP in permeabilized normal human lymphocytes.
When peripheral lymphocytes stimulated with phytohemagglutinin were permeabilized in vitro, (3H) dCTP acted as a precursor for DNA synthesis, but the formation of a compound soluble in organic solvents could also be demonstrated. The structure of the latter compound was studied analyzing the products formed after alkaline hydrolysis or an enzymatic treatment with nucleotide pyrophosphatase. Both treatments led to the formation of (3H)dCMP. When stimulated lymphocytes were labeled in vivo with (14C)glycerol before permeabilization and ulterior labeling with (3H)dCTP a double labeled compound was obtained. When this compound was submitted to alkaline hydrolysis, (3H)dCMP and (14C)glycerol-3-phosphate were obtained. It was concluded that the compound soluble in organic solvents was phosphatidyl-dCMP.


Post-death burial and funeral practices in rural Alberta.
Burial and funeral practices are important customary mortuary rituals, especially in rural areas as people are likely to have different values and interests than people who live in larger cities. However, little is known about rural post-death practices in Canada. This review gathered information on funeral and burial practices in rural Alberta, a western Canadian province with a diverse rural population. A literature review of community print sources, including obituaries and funeral home websites, was conducted for select representative rural communities. This review found that cremations outnumber burials, and mortuary ceremonies more commonly occur in non-religious settings. Furthermore, personalised post-death rituals were identified as highly significant to rural people as they allow the dead to remain connected to their rural land, family and community. It is important to understand rural mortuary rituals to help prepare dying rural people and their families.


Formation of lipoidal steroids in follicular fluid.
The presence of high levels of lipoidal pregnenolone in follicular fluid has recently been established although no evidence has been presented concerning its possible origin. The following investigation focuses on the enzymatic conversion of non-conjugated steroids into their lipoidal derivatives in preovulatory follicular fluid obtained from women undergoing in vitro fertilization. Our observations indicated that pregnenolone, an important precursor steroid, was acylated at a similar rate as cholesterol in follicular fluid. Similar studies were subsequently conducted with serum obtained from a pool of normal women and women undergoing follicular stimulation which showed little difference to the results obtained in follicular fluid. Further studies using dehydroepiandrosterone, androst-5-ene-3 beta,17 beta-diol, estradiol and dihydrotestosterone were were also performed to monitor their respective lipoidal conversion percentages in follicular fluid which revealed a marked difference of conversion rates between steroids. The indirect identification of the lipoidal pregnenolone derivatives formed in follicular fluid was also conducted by incubating radiolabelled pregnenolone in follicular fluid. The fatty acid components of the resulting lipoidal pregnenolone derivatives showed a marked resemblance to those of cholesteryl esters formed in plasma by the enzymatic activity of lecithin:cholesterol acyltransferase. The pregnenolone derivatives were comprised predominantly of unsaturated fatty acids such as linoleate, palmitoleate, oleate, linolenate and arachidonate while saturated fatty acids, namely palmitate, constituted 20% of the total lipoidal pregnenolone.


A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation.
Four small ubiquitin-related modifier (SUMO) genes have been identified in humans. However, little is known about the basic biology of SUMO-4. Here, we report that SUMO-4 differs from SUMO-1, -2, and -3 in that the maturation process of SUMO-4 to active form containing C-terminal di-glycine residues is inhibited by a unique proline residue located at position 90 (Pro-90). Although, both the hydrolase and isopeptidase activities of SUMO peptidases are significantly diminished by Pro-90 as compared to Gln-90 (glutamine) in mutated SUMO genes, only the defective hydrolase activity appears to be biologically relevant. Native SUMO-4, thus, appears to be unable to form covalent isopeptide bonds with substrates. A biological role of SUMO-4, through non-covalent interactions is proposed.


Pharmacy Practice Standards for Outpatient Nephrology Settings.
Patients with kidney disease represent a medically complex group of patients with high medication burdens that could benefit from clinical pharmacy services as part of the interdisciplinary care team to optimize medication use. The "Advancing American Kidney Health" executive order includes new value-based reimbursement models to be tested by the Center for Medicare and Medicaid Innovation beginning January 2021 and January 2022. Advancing American Kidney Health executive order poses opportunities for the inclusion of comprehensive medication management. Following an iterative process integrating input from a diverse expert panel, published standards, clinical practice guidelines, peer review, and stakeholder feedback, our group developed practice standards for pharmacists caring for patients with kidney disease in health care settings. The standards focus on activities that are part of direct patient care and also include activities related to public health and advocacy, population health, leadership and management, and teaching, education and dissemination of knowledge. These standards are intended to be used by a variety of professionals, from pharmacists starting new practices to practice managers looking to add a pharmacist to the clinical team, to create standardization in services provided.


One-stage multiple root canal treatment of adjacent teeth combined with surgical apicectomies may be preferred in patients with severe anxiety under local anaesthesia: a case report.
A female patient referred to the clinic for assessment of a unilateral painful swelling formation on the left anterior maxilla. Anxiety is a psychological condition commonly seen in dental practice. When this psychological alteration affects the patient severely, any dental operation may be found difficult under local anaesthesia. We report a case of one-stage management in a patient with periapical lesion and anxiety.


Evaluation of cultivar susceptibility and storage periods towards aflatoxin B1 contamination on pistachio nuts.
Aflatoxins (AFs) are potent sources of health risks to both humans and animals. Among them, AFB1 is the most hazardously toxic and the most frequent in various food commodities, including pistachio nuts. In this survey, the effect of the storage period on AFB1 accumulation on pistachio nuts was investigated. A total of 49 samples collected during the crop year of 2005 from the most cultivated pistachio cultivars in Tunisia were rapidly screened by enzyme-linked immunosorbent assay (ELISA) combined with an immunoaffinity step. The obtained results showed that the contamination of pistachio nuts has occurred clearly after two years of storage for all the tested cultivars except the case of Mateur variety and Thyna ecotypes. In this study, the cultivar Mateur was found to be the most susceptible cultivar to contamination by AFB1. After 4 years of storage, the average contamination levels in nut samples ranged from 2.7 ± 0.3 to 12.7 ± 2.2 µg/kg for AFB1, according to the cultivar. These levels exceeded the maximum permitted limit of 2 µg/kg set by the European Commission in nuts.


Adversarial feature hybrid framework for steganography with shifted window local loss.
Image steganography is a long-standing image security problem that aims at hiding information in cover images. In recent years, the application of deep learning to steganography has the tendency to outperform traditional methods. However, the vigorous development of CNN-based steganalyzers still have a serious threat to steganography methods. To address this gap, we present an end-to-end adversarial steganography framework based on CNN and Transformer learned by shifted window local loss, called StegoFormer, which contains Encoder, Decoder, and Discriminator. Encoder is a hybrid model based on U-shaped network and Transformer block, which effectively integrates high-resolution spatial features and global self-attention features. In particular, Shuffle Linear layer is suggested, which can enhance the linear layer's competence to extract local features. Given the substantial error in the central patch of the stego image, we propose shifted window local loss learning to assist Encoder in generating accurate stego images via weighted local loss. Furthermore, Gaussian mask augmentation method is designed to augment data for Discriminator, which helps to improve the security of Encoder through adversarial training. Controlled experiments show that StegoFormer is superior to the existing advanced steganography methods in terms of anti-steganalysis ability, steganography effectiveness, and information restoration.