Temperament in full-term and preterm infants: stability over ages 6 to 24 months.
Temperament stability over successive ages in the first 2 years of life was evaluated for 109 full-term and 81 preterm infants who were assessed at 6, 9, 12, 18, and 24 months. At each age, the infant was engaged in a series of age-appropriate vignettes in the laboratory, using a structured sequence of activities. Ratings were made of emotional tone, attentiveness, activity, and orientation to staff. Correlations indicated that, for full-term infants, there was significant stability across ages (6 to 9 months, 9 to 12 months, 12 to 18 months, and 18 to 24 months) for all variables. For preterm infants, stability across ages generally was not observed until later infancy, or was sporadic. The findings indicated that, for full-term infants, stable aspects of temperament were apparent during the first year of life. In contrast, individual differences were not as clearly defined for preterm infants until later ages.


Hydrodynamic flow and concentration gradients in the gut enhance neutral bacterial diversity.
The gut microbiota features important genetic diversity, and the specific spatial features of the gut may shape evolution within this environment. We investigate the fixation probability of neutral bacterial mutants within a minimal model of the gut that includes hydrodynamic flow and resulting gradients of food and bacterial concentrations. We find that this fixation probability is substantially increased, compared with an equivalent well-mixed system, in the regime where the profiles of food and bacterial concentration are strongly spatially dependent. Fixation probability then becomes independent of total population size. We show that our results can be rationalized by introducing an active population, which consists of those bacteria that are actively consuming food and dividing. The active population size yields an effective population size for neutral mutant fixation probability in the gut.


Ethnic indicators of dental health for young Asian schoolchildren resident in areas of multiple deprivation.
The aim of the study was to explore the use of two social indicators in a dental caries epidemiological study of 5-year-old Asian schoolchildren in an area of multiple deprivation. The two indicators selected were religious background and the mother's ability to speak English. Six hundred and forty-three 5-year-old schoolchildren from three schools were examined; the mean dmft was 2.84 (SD 3.63). Children were classified into three groups on broad ethnic/facial characteristics, and the mean dmft for Asians (3.64) differed statistically significantly from those of both Whites (1.83) and Afro-Caribbeans (1.87). When the Asian population was divided into four groups, to explore the effects of religion and the mother's ability to speak English, a statistically significant interaction was observed between religion and language for mean dmft and dental cleanliness. The Asian non-Muslim children whose mothers were English speaking (ES) compared well with the White and Afro-Caribbean group for mean dmft, percentage caries-free and oral cleanliness. When these variables were examined for the two Muslim groups and the non-Muslim group whose mothers were non-English speaking (NES), no statistically significant differences were observed. Oral health promotion should therefore consider that there are three distinct dental high-risk groups for young Asian children: Muslim ES and NES mothers and non-Muslim NES mothers. Each group will require a different health promotion strategy. Non-English speaking mothers need adequate translation, whereas all Muslim mothers need help to find proper alternatives to baby-foods which, although common in the UK, are culturally inappropriate to Muslims.


Comparison of apical left ventricular segments strain imaging by tissue Doppler and speckle tracking echocardiography.
Spatial orientation of left ventricular (LV) apical segments is a potential limitation to assessment by tissue Doppler echocardiography (TDE). Speckle tracking echocardiography (STE) is a recently developed quantification technique and has the advantage of being angle-independent as compared to TDE. To assess matching apical segments' longitudinal strain data from TDE and STE. A 16-segment LV model was used. The study was based on a dataset of 306 myocardial segments from 22 consecutive patients with various degrees of wall motion abnormalities. 82 available apical lateral, septal, anterior and inferior segments from 2-chamber and 4-chamber views were selected for further assessment. The Bland-Altman method was used for comparison of mean strain values of corresponding segments. An acceptable overall agreement between the two modalities was shown by the Bland-Altman method. The correlation ratio was 0.7. The measurements of apical lateral and anterior segments' longitudinal strain showed no significant difference. Speckle tracking echocardiography tended to produce lower strain results than TDE with mean values of -9 and -14%, respectively, p=0.0025. Although angle-dependency of TDE may be a potential limitation in the strain imaging of apical LV segments, the overall agreement between TDE and angle independent STE technique is still acceptable.


In situ method for the determination of nutrient acquisition and its hormonal regulation in the spiral valve of two chondrichthyan fishes.
Chondrichthyans play an important role in nutrient cycling of many marine ecosystems, yet little is known about their nutritional physiology particularly relating to nutrient acquisition in the spiral valve intestine. This unique organ poses challenges for examining nutrient transport physiology using traditional reductionist methods owing to its scroll-like morphology. Thus, we established a method for the characterization of nutrient uptake rates in two representative chondrichthyans, the Pacific spiny dogfish (Squalus suckleyi) and the Pacific spotted ratfish (Hydrolagus colliei). We validated a dual-cannulation method wherein perfusate was circulated through the vasculature of the spiral valve via the anterior and posterior intestinal arteries, and [14C]glucose or [3H]oleic acid was accumulated from the static spiral valve lumen into the anterior and posterior intestinal veins. Radiotracer accumulated at a stable rate in the venous effluent in comparison with measures of mucosal disappearance. Interestingly, similar anterior and posterior glucose uptake was observed in dogfish, yet significantly more oleic acid was accumulated in the posterior veins of ratfish. Further validation of the preparation in dogfish demonstrated sodium dependence of glucose transport as well as an effect of bovine insulin administration to the arterial circulation. Each of these manipulations resulted in significant differences in glucose handling between the anterior and posterior veins, suggestive of heretofore unknown heterogenous functions along the intestine. This preparation demonstrates a new and reliable method for the measurement of nutrient acquisition and regulation thereof in a unique digestive organ. Furthermore, it presents avenues for investigation of differential functional along the spiral valve.NEW & NOTEWORTHY We describe a novel dual cannulation method for investigating radiolabeled nutrient uptake from a unique organ, the spiral valve. Furthermore, we identify functional differences in nutrient transport along the length of the spiral valve which consists of a homogenous gross morphology. Finally, this method reveals a useful way in which to manipulate the arterial supply to better understand postprandial physiology as it varies with metabolites and endocrine factors.


A Comparative Study on Breast Milk Feeding and Formula Milk Feeding in Infants With Congenital Heart Disease After Surgery: A Retrospective Study.
To explore the effects of breast milk feeding and formula milk feeding on infants after cardiac surgery in the cardiac intensive care unit (ICU). Infants who underwent cardiac surgery in our ICU were divided into two groups, according to feeding type. Breast milk feeding and formula milk feeding were separately implemented in the two groups, and the remaining treatment regimens were the same. The related clinical data and feeding effects were recorded and compared. The prealbumin (147.3 ± 15.2 versus 121.5 ± 18.3mg/L) and albumin (46.4 ± 4.2 versus 40.5 ± 5.1 g/L) levels in the breast milk feeding group were better than those in the formula milk feeding group (P < .05). Infants in the breast milk feeding group achieved a better total enteral nutrition time (3.0 ± 1.2 versus 5.2 ± 2.1 d), average daily weight gain (19.0 ± 3.4 versus 14.4 ± 2.3 g/kg·d), length of ICU stay (6.0 ± 2.2 versus 8.1 ± 2.9 d) and length of hospital stay (13.9 ± 4.2 versus 17.8 ± 5.6 d) than those in the formula milk feeding group (P < .05). The incidence of complications such as feeding intolerance, anemia, dyspeptic diarrhea, and nosocomial infection was lower in the breast milk feeding group than in the formula milk feeding group (P < 0.05). Breast milk feeding has a definite nutritional effect on infants after cardiac surgery. It is better than formula milk feeding, making it worthy of popularization and application.


White Matter Microstructure is Associated with Serum Clusterin and Everyday Functioning in a Sample of Nondemented Older Adults.
Although clusterin-a protein involved in lipid metabolism, amyloid beta clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at risk for Alzheimer's disease, research exploring associations with white matter (WM) micro- and macro- structural markers are largely limited. The current study explored associations between serum clusterin protein levels and WM micro- and macro- structural markers, and clarified whether variations in WM fractional anisotropy (FA) were associated with functional abilities within in a racially homogenous sample of relatively well-educated older adults free of dementia. Participants underwent magnetic resonance imaging (MRI) brain exams and a blood draw and completed a performance-based measure of everyday functioning. Multiple linear regression adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin associations with WM metrics, as well clarify potential links between WM microstructure and everyday functioning. Higher serum clusterin was associated with lower FA in several thalamocortical (anterior and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02). Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but higher FA of several WM tracts was associated with better performance on the Independent Living Scale (ßs = .37 to .53, ps = .006 to .03). Serum clusterin is differentially associated with WM metrics, and WM microstructure is associated with everyday functioning.


Laryngopharyngeal reflux disease treated with laparoscopic fundoplication.
The objective of this clinical prospective study was to find out if laparoscopic Nissen fundoplication is an effective treatment in laryngopharyngeal reflux disease. Twenty-two consecutive patients, 16 female and 6 male, who were referred to laparoscopic fundoplication and operated by a senior gastroenterology surgeon were included in this study. Their mean age was 41 years (SD 13), and ranged from 18 to 64. The patients selected for surgical treatment had LPRD with several vocal and laryngeal symptoms. The status findings were typical for laryngopharyngeal reflux and the symptoms and signs had responded to antireflux medication. Vocal symptoms were interviewed and patients underwent laryngoscopy, esophagogastroscopy, and 24-h esophageal pH monitoring. The follow-up of symptoms and signs were 3 months after beginning of medication, before surgery, 3 months, and 1 year after surgery. The number of patients experiencing vocal symptoms decreased during the medical treatment, from the situation before medical treatment to the situation before surgery (P < 0.001), from the situation before surgery to the situation 3 months (P < 0.001) and 1 year post operation (P < 0.001), but no significant changes were found from the situation 3 months to 1 year post operation. Voice quality improved significantly only from the time point before surgery to 3 months post operation. Three months after medical treatment, laryngeal and pharyngeal findings did not decrease significantly, but several findings decreased significantly (P < 0.001) from the time point before surgery compared to 3 months and to 1 year post operation. Based on this study, the laparoscopic fundoplication is an effective and safe treatment of LPRD.


Long-term therapeutic efficacy of lipoprotein apheresis on circulating oxidative stress parameters--A comparison of two different apheresis techniques.
A chronic lipoprotein apheresis therapy leads to an expressed reduction in the incidence of cardiovascular events in high-risk patients. In addition to the elimination of atherogenic lipoproteins such as LDL and lipoprotein(a), an antioxidative effect of lipoprotein apheresis has been suspected. We investigated long-term biochemical effects in sixteen patients undergoing lipoprotein apheresis - lipid filtration (LF, n = 7) or dextran sulfate adsorption (DSA, n = 9). Systemic oxidative stress markers (blood phagocyte chemiluminescence, levels of oxidized LDL and antioxLDL antibodies) were examined at the 1st, 40th and 80th apheresis sessions. In DSA patients, the 80th apheresis session was associated with significantly higher LDL cholesterol removal and lower HDL cholesterol deprivation as compared to LF patients. In contrast to LF patients, DSA patients showed a long-term progressive decrease in circulating oxidant generating activity as evaluated by whole blood chemiluminescence (p < 0.05). Moreover, a single LF apheresis session was associated with higher systemic generation of reactive oxygen species over time. Compared to LF, long-term DSA apheresis is associated with a gradual reduction of circulating oxidative burden and may be considered a beneficial molecular mechanism of this technique.


[Spermatogenesis--physiology and pathophysiology].
Spermatogenesis takes place within the testicular seminiferous tubules which consist of the peritubular lamina propria and the seminiferous epithelium. The latter is composed of germ cells and somatic Sertoli cells. Sertoli cells trigger germ cell development by mediating follicle-stimulating hormone and androgen hormonal stimuli.Spermatogenesis comprises proliferation of spermatogonia, meiosis of spermatocytes, and differentiation of spermatids into spermatozoa (spermiogenesis). There are six distinct and specific germ cell associations (I-VI). These "stages of spermatogenesis" occur sequentially along the length of a tubule. Different defects in spermatogenesis occur in adjacent seminiferous tubules (mixed atrophy) and are associated with deficits in differentiation of Sertoli cells. Biopsy specimens should be fixed in Bouin's solution. Diagnosis of preinvasive carcinoma in situ is based on the immunohistochemical demonstration of placental-like alkaline phosphatase (PLAP), which is expressed exclusively in carcinoma in situ cells. Histological evaluation should be performed using a score count system, and the use of histological techniques for protein and mRNA expression. Testicular biopsy should only be performed in accordance with strict indication criteria, and histological evaluation should be carried out in specialist centres, i.e. as recommended by the European Academy of Andrology (EAA).


New flavonol glycosides from the leaves and flowers of Primula sieboidii.
Three flavonol glycosides were isolated from the leaves of Primula sieboldii. They were identified as quercetin 3-O-β-[xylopyranosyl-(1-->2)-β- glucopyranosyl-(1-->6)-β-glucopyranoside] (1), kaempferol 3-O-β-[glucopyranosyl-(1-->2)-β-glucopyranosyl-(1-->6)-β-glucopyranoside] (2) and kaempferol 3- O-β-[xylopyranosyl-(1-->2)-β-glucopyranosyl-(1-->6)-β-glucopyranoside] (3). Their chemical structures were determined by UV, 1H and 13C NMR spectroscopy, LC-MS and acid hydrolysis. Compounds 1 and 3 are found in nature for the first time. They were also detected in the flowers, together with two anthocyanins, malvidin 3,5-di-O-glucoside and a minor petunidin dihexoside.


Dynamic adsorption of monoclonal antibody layers on hydrophilic silica surface: a combined study by spectroscopic ellipsometry and AFM.
Spectroscopic ellipsometry (SE) and atomic force microscopy (AFM) have been used to investigate the adsorption of a mouse monoclonal antibody (type IgG1, anti-beta-hCG) on hydrophilic silica (bearing weak negative charges above pH 3), followed by the assessment of binding of human chorionic gonadotrophin (hCG). The antibody is a relatively large molecule with a molecular weight of 150 kDa and the isoelectric point (IP) around pH 6. The antibody adsorption was conducted at pH 4.0, 6.0 and 8.0 to examine the role of charge interaction. Ellipsometric results show that away from the IP, both initial adsorption rate and surface excess decreased, with the reduction at pH 8.0 being more pronounced than that at pH 4.0 due to the electrostatic repulsion not only between the charged antibody molecules within the adsorbed layer but also between antibody and the silica surface. Whilst parallel AFM measurements confirmed the main trend of pH dependent antibody adsorption, they also revealed the tendency of surface aggregation with increasing surface coverage. AFM height profiling at low surface coverage confirmed the "flat-on" orientation of adsorbed antibody molecules, consistent with the previous study by neutron reflection. Interestingly, the antibody height at pH 4.0 was found to be lower than that at pH 8.0, showing the influence from different electrostatic interactions under the two pH conditions. Subsequent hCG binding to the adsorbed antibodies was found to decrease with increasing surface coverage due to the steric hindrance. Under similar antibody surface coverage, the hCG binding ratio at pH 8 was higher than that at pH 4.0, a difference that could only be accounted for by the tighter surface confinement at pH 4.0.


Wastewater cleanup using Phlebia acerina fungi: An insight into mycoremediation.
The scarcity of available drinking water has led the researchers to develop novel and cost-effective ways of bioremediation process for wastewater treatment. Bioremediation is a cost-effective and environmentally sound method for the removal of toxic compounds. Such approach is not only a chemical-less effort but also an energy savior. In the present work Phlebia acerina, a white rot wood rotting fungi have been used to degrade the toxic wastewater pollutants. Congo Red (CR) and Eriochrome Black T (EBT) have been selected as model pollutants to test the wastewater cleaning ability of the fungus. The Lignin modifying enzyme (LME) and Cellulolytic enzyme assays (CMC) potential of Phlebia acerina helped in understanding the dye degradation mechanism. Under the optimum conditions, the fungi was able to degrade as high as 92.4% CR while the EBT was degraded to a maximum of 50%. Phlebia acerina was found to show first-order kinetics of dyes degradation. Further, the seed germination and antimicrobial assay of treated and untreated water were carried out in order to establish the formation of non-toxic end product after degradation.


Retroperitoneal Hematoma: A Sequela of Acute Hemorrhagic Pancreatitis Post Endoscopic Retrograde Cholangiopancreatography.
Endoscopic retrograde cholangiopancreatography (ERCP) is a diagnostic and therapeutic tool for pancreaticobiliary diseases. Like every other procedure, ERCP can lead to complications that include pancreatitis, cholecystitis, perforation, and rarely, retroperitoneal hematoma. We present a case of post-ERCP acute hemorrhagic pancreatitis resulting in retroperitoneal hematoma and sequelae of unilateral hydronephrosis and ileus. The patient was treated supportively and had good clinical improvement with resolution of hydronephrosis, ileus and more importantly tolerating oral diet without further episodes of abdominal pain. The most common complications of endoscopic retrograde cholangiography are acute pancreatitis and hemorrhage. In high-risk patients, acute pancreatis can be prevented with rectal non-steroidal anti-inflammatory suppository before the procedure.Occurrence of Grey-Turner or Cullen sign should prompt immediate search for retroperitoneal hematoma especially in the setting of acute hemorrhagic pancreatitis.Apart from hemodynamic instability or compressive symptoms, retroperitoneal hematoma can also cause complications due to inflammatory reactions resulting in hydronephrosis or ileus.


Peri-implantation expression and regulation of ITGB8 in goat uterus.
Ruminants have a superficial implantation pattern. The extended conceptus attaches to the receptive endometrium to form the cotyledonary placenta. During the attachment, a large number of events occur at the maternal-fetal interface. However, the related molecular mechanisms have not been fully understood. Integrin beta8 (ITGB8) is a subunit of integrin beta involved in embryo implantation. In this study, we determined peri-implantation expression and regulation of ITGB8 in goat uterus. The mRNA and protein levels of ITGB8 were both high in goat endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) during the adhesion period (Days 16-19 of pregnancy). Such expression profile was opposite to that of microRNA-187 (miR-187). Then, we validated that miR-187 targeted the 3' untranslated region (UTR) of ITGB8 in primary goat endometrial epithelial cells (EECs). In EECs, inhibition of miR-187 resulted in not only up-regulated ITGB8 level but also reduced cell proliferation and focal adhesion kinase (FAK) activity. Moreover, ITGB8 and miR-187 were regulated by interferon tau (IFNT). Altogether, in goat, the miR-187/ITGB8 axis may be involved in conceptus attachment and is downstream of IFNT. Our results will help us better understand the mechanisms of ruminant implantation and may provide a useful tool to improve the reproduction ratio for ruminants.


A useful technique of starting internal limiting membrane peeling from the edge of the internal limiting membrane defect in epiretinal membrane surgery.
Clinicians should be aware that internal limiting membrane (ILM) defects may occur concurrently with epiretinal membrane, and starting ILM peeling at the ILM defect margin may be useful in such cases. We describe a useful surgical technique for the treatment of idiopathic epiretinal membrane with concurrent internal limiting membrane (ILM) defect, in which ILM peeling was started from the ILM defect margin. A dissociated optic nerve fiber layer-like appearance on fundus examination and optical coherence tomography may suggest an ILM defect.


Impact of surgical instrumentation on hospital length of stay and cost of total knee arthroplasty.
We aimed to analyze the impact of two different types of surgical instrumentation (conventional manual instrumentation (CI) and patient-specific instrumentation (PSI)) on length of stay (LOS) and objectify differences in cost. We hypothesized that there are no differences in the LOS and cost due to the instrumentation system used. LOS was registered using inpatient admission data provided by the Institutional Management Control Department. We recorded the costs associated with each procedure that could be influenced by the use of one system or another during the in-hospital stay. We conducted a prospectively single-center cohort study of 305 TKAs. Surgery was performed with conventional CI in 122 cases and with PSI in 183 cases. The mean LOS for the CI group was 4.29 days (SD 1.65) and 4.22 days (SD 1.26), for the PSI group. No significant difference among both instrumentation systems was obtained. When comparing global costs, the mean cost was slightly higher (without a significant difference) for the PSI cases (€3110.24 vs. €2852.7 for the CI cases). LOS and overall cost, in hospitals with a low annual TKA surgery volume, are unrelated to conventional or patient-specific instrumentation.


Point-of-care ultrasound in diagnosing pyomyositis: a report of three cases.
Pyomyositis is a bacterial infection of skeletal muscle that often results in deep intramuscular abscesses. The absence of external dermatologic manifestations in the early stages of pyomyositis makes this a challenging diagnosis. In addition, physical examination findings can be difficult to distinguish from more common processes, such as soft-tissue cellulitis. Clinicians can fail to diagnose this serious disease in a timely manner, resulting in delayed treatment and potential clinical deterioration from sepsis. Although advanced imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI) provide excellent detail, ultrasound (US) can also be used to detect this disease. US can be performed expeditiously at the bedside and is less expensive than CT or MRI. It allows the clinician to examine the deeper tissue planes of muscle, in which purulent fluid collections will develop as pyomyositis advances. Three patients presenting with leg pain were evaluated with point-of-care (POC) US and diagnosed with pyomyositis. The early diagnosis of this condition prompted rapid treatment with administration of appropriate antibiotics and involvement of orthopedic surgery. Aspiration of fluid allowed for detailed fluid analysis and bacterial cultures. Additional diagnostic imaging was performed, confirming the initial US diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POC US can be helpful in identifying and further delineating intramuscular abscesses and can subsequently lead to expedited and appropriate care in patients who present with extremity pain, but lack significant dermatologic changes.


Ethanol perturbs lipid organization in models of stratum corneum membranes: An investigation combining differential scanning calorimetry, infrared and (2)H NMR spectroscopy.
Ethanol is used in a variety of topical products. It is known to enhance the permeability of the skin by altering the ability of the stratum corneum (SC) intercellular membranes to form an effective barrier. In addition, ethanol and other alcohols are key components of antiseptic gels currently used for hand wash. Using infrared and deuterium NMR spectroscopy as well as calorimetry, we have investigated the effect of ethanol on a model membrane composed of lipids representing the three classes of SC lipids, an equimolar mixture of N-palmitoylsphingosine (ceramide), palmitic acid and cholesterol. Ethanol is found to influence the membrane in a dose dependent manner, disrupting packing and increasing lipid motion at low concentrations and selectively extracting lipids at moderate concentrations.


Studies on antibacterial dressings obtained by fluorinated post-discharge plasma.
Surface modification of wool, polyamide 6 and cotton fabrics was investigated with an Ar-CF(4) post-discharge plasma. The radical F, as determined by optical emission spectroscopy, is considered to be the main active species acting on the fabrics and producing different effects as a function of the textile substrate. Fluorination of the surface is achieved on the three materials studied, but only wool and polyamide 6 fluorinated surfaces become hydrophobic at long treatment times, and show antibacterial properties. The treatment conditions used are mild enough so as not to alter surface topography, as confirmed by scanning electron and atomic force microscopy.


Echo Memory-Augmented Network for time series classification.
Echo State Networks (ESNs) are efficient recurrent neural networks (RNNs) which have been successfully applied to time series modeling tasks. However, ESNs are unable to capture the history information far from the current time step, since the echo state at the present step of ESNs mostly impacted by the previous one. Thus, ESN may have difficulty in capturing the long-term dependencies of temporal data. In this paper, we propose an end-to-end model named Echo Memory-Augmented Network (EMAN) for time series classification. An EMAN consists of an echo memory-augmented encoder and a multi-scale convolutional learner. First, the time series is fed into the reservoir of an ESN to produce the echo states, which are all collected into an echo memory matrix along with the time steps. After that, we design an echo memory-augmented mechanism employing the sparse learnable attention to the echo memory matrix to obtain the Echo Memory-Augmented Representations (EMARs). In this way, the input time series is encoded into the EMARs with enhancing the temporal memory of the ESN. We then use multi-scale convolutions with the max-over-time pooling to extract the most discriminative features from the EMARs. Finally, a fully-connected layer and a softmax layer calculate the probability distribution on categories. Experiments conducted on extensive time series datasets show that EMAN is state-of-the-art compared to existing time series classification methods. The visualization analysis also demonstrates the effectiveness of enhancing the temporal memory of the ESN.


Mechanisms and kinetics of humic acid adsorption onto chitosan-coated granules.
Chitosan, a naturally abundant biopolymer, has widely been studied for metal adsorption from various aqueous solutions, but the extension of chitosan as an adsorbent to remove humic substances from water has seldom been explored. In this study, chitosan was coated on the surface of polyethyleneterephthalate (PET) granules through a dip and phase inversion process and was examined for humic acid removal in a series of batch adsorption experiments. Scanning electron microscopic (SEM) images showed that the PET granules were uniformly covered with a layer of chitosan and the chitosan layer possessed numerous open pores on the surface. Zeta potential study indicated that the chitosan-coated granules had positive zeta potentials at pH < 6.6 and negative zeta potentials at pH > 6.6. Adsorption of humic acid onto the chitosan-coated granules was found to be strongly pH-dependent. Significant amounts of humic acid were adsorbed under acidic and neutral pH conditions, but the adsorption capacity was reduced remarkably with increasing solution pH values. The adsorption isothermal data under various initial humic acid concentrations (at the same solution pH value) can be adequately modeled by the Langmuir and Freundlich models. X-ray photoelectron spectroscopy (XPS) revealed that the amino groups of the chitosan layer were protonated due to humic acid adsorption, suggesting the formation of organic complex between the protonated amino groups and humic acid. Kinetic study indicated that the adsorption process was transport-limited at low solution pH values, but became both transport- and attachment-limited at high solution pH values.


Possible role of the carbohydrate residues in the display of the MN blood group determinants by glycophorin A.
Heterozygous glycophorin AM,N and homozygous glycophorin AM were reductively methylated with 13C-enriched formaldehyde in the presence of cyanoborohydride. Total reductive methylation modified the five lysine residues, and the N-terminal amino acid residues (serine and leucine) of glycophorins AM and AN, respectively. The 13C resonances of the incorporated labels were monitored as a function of the degree of glycosylation of the glycoprotein. While minimal, if any, structural changes were observed near the N-terminal amino acid upon removal of alpha-D-N-acetylneuraminic acid residues, gross structural changes were observed when most of the oligosaccharide chains were removed. We also found that progressive methylation of the lysine residues of glycophorin AM may influence either the chemical shift of one of the nonequivalent methyl groups of the N alpha, N-[13C]dimethyl serine residue, or one of the two states of glycophorin AM.


Defining and assessing competence: the distraction of outcomes and the importance of educational process.
The concept of competence is in common usage in various areas of education and training at present, and it is evident from these different usages that it has a variety of meanings. These meanings are explored, with particular attention being paid to the increasing influence of the National Vocational Qualification (NVQ) initiative and the rise of vocational education. It is concluded that the utilization of competence within these fields offers little to nurse/midwifery education (with the exception of a refocusing on the concept of skills) because it is exactly that: education, and is therefore different in some significant aspects from training and vocational approaches. It is suggested that a holistic conceptualization of competence is the most appropriate for nurse/midwifery education: one that empowers students and practitioners, facilitating critical thinking, rather than emphasizing, as the NVQ initiative does, outcomes over the importance of educational process and the use of a variety of forms of knowledge in practice. It is acknowledged that there is probably a skills deficit in some areas of nursing/midwifery education, although definition of this term 'skills' remains problematic, and that this should be addressed through the increased use of skills laboratories.


Individual capacity differences predict working memory performance and prefrontal activity following dopamine receptor stimulation.
Dopamine receptors are abundant in the prefrontal cortex (PFC), a critical region involved in working memory. This pharmacological fMRI study tested the relationships between dopamine, PFC function, and individual differences in working memory capacity. Subjects performed a verbal delayed-recognition task after taking either the dopamine receptor agonist bromocriptine or a placebo. Behavioral effects of bromocriptine treatment depended on subjects' working memory spans, with the greatest behavioral benefit for lower span subjects. After bromocriptine, PFC activity was positively correlated with a measure of cognitive efficiency (RT slope) during the probe period of the task. Less efficient subjects with slower memory retrieval rates had greater PFC activity, whereas more efficient subjects had less activity. After placebo, these measures were uncorrelated. These results support the role of dopamine in verbal working memory and suggest that dopamine may modulate the efficiency of retrieval of items from the contents of working memory. Individual differences in PFC dopamine receptor concentration may thus underlie the behavioral effects of dopamine stimulation on working memory function.


Synthesis and evaluation of resveratrol derivatives as new chemical entities for cancer.
Resveratrol has been shown to be active in inhibiting multistage carcinogenesis. The potential use of resveratrol in cancer chemoprevention or chemotherapy settings has been hindered by its short half-life and low bioavailability. Considering the above remarks, using resveratrol as a prototype, we have synthesized two derivatives of resveratrol. Their activity was evaluated using in vitro and in silico analysis. Biological evaluation of resveratrol analogues on U937 cells had shown that two synthesized analogues of resveratrol had higher rates of inhibition than the parental molecule at 10μM concentration. EMSA conducted for NF-kB revealed that these molecules significantly interfered in the DNA binding ability of NF-kB. It was found that these molecules suppressed the expression of TNFα, TNFR, IL-8, actin and activated the expression of FasL, FasR genes. To understand possible molecular mechanism of the action we performed docking and dynamic studies, using NF-kB as a receptor. Results showed that resveratrol, RA1 and RA2 interacted with the residues involved in DNA binding. Resveratrol analogues by interacting NF-kB might have prevented its translocation and also by interacting with the residues involved in DNA binding might have prevented the binding of NF-kB to DNA. This may be the reason for suppression of NF-kB binding to DNA.


A simple in vitro method of radiolabelling human erythrocytes in whole blood with 113mIn-tropolonate.
A simple and rapid in vitro procedure has been developed for selectively radiolabelling erythrocytes in whole blood using 113mIn-tropolonate. A maximum labelling efficiency of 97% was achieved, of which 95.5% was on the erythrocytes after only 5 min incubation of whole blood at room temperature. The optimum amount of tropolone for labelling whole blood was 10 micrograms of tropolone per ml of blood using acid-citrate dextrose (ACD) as the anticoagulant and 50 micrograms of tropolone per ml of blood using heparin. Under these optimum conditions, only 2.5% of the cell-bound 113mIn was released from the labelled cells during a 1 h in vitro incubation in cell-free plasma, irrespective of the anticoagulant used. These results suggest that 113mIn-tropolonate may prove to be a useful in vitro agent for labelling erythrocytes for short-term clinical investigations, especially at centres where 99mTc and 111In are unavailable.


Development of novel dipeptide nitriles as inhibitors of rhodesain of Trypanosoma brucei rhodesiense.
In this paper, we developed a new series of dipeptide nitriles that were demonstrated to be reversible rhodesain inhibitors at nanomolar level, with EC50 values against cultured T. b. brucei in the micromolar range. We also proved that our dipeptide nitriles directly bind to the active site of rhodesain acting as competitive inhibitors. Within the most interesting compounds, the dipeptide nitrile 2b showed the highest binding affinity towards rhodesain (Ki = 16 nM) coupled with a good antiparasitic activity (EC50 = 14.1 μM). Moreover, for the dipeptide nitrile 3e, which showed a Ki = 122 nM towards the trypanosomal protease, we obtained the highest antiparasitic activity (EC50 = 8.8 μM). Thus, given the obtained results both compounds could certainly represent new lead compounds for the discovery of new drugs to treat Human African Trypanosomiasis.


From the American Epicenter: Coronavirus Disease 2019 in Patients with Inflammatory Bowel Disease in the New York City Metropolitan Area.
We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn's disease or older men with comorbidities, and 1 patient expired. In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.


Long-term retention after structured curriculum on attainment of critical view of safety during laparoscopic cholecystectomy for surgeons.
Obtaining a clear Critical View of Safety helps prevent bile duct injuries during laparoscopic cholecystectomy, which can be improved with a structured Safe Critical View of Safety curriculum. We aimed to determine whether the improvement in obtaining Critical View of Safety postcurriculum is retained long-term. A safe Critical View of Safety curriculum was previously implemented for all surgeons who perform laparoscopic cholecystectomy at a regional health system. Recordings of laparoscopic cholecystectomy cases were collected 1 year after completion of the curriculum, deidentified and randomly ordered, and then graded by 2 blinded expert surgeons using a 6-point Critical View of Safety assessment tool. A total of 12 surgeons with average experience of 17.9 ± 6.3 years in practice participated in the study. The majority (83%) had performed >700 laparoscopic cholecystectomies, and 4 surgeons (33%) reported 2 or more bile duct injuries in their career. Controlling for gallbladder pathology, Critical View of Safety scores improved from 1.7 ± 0.4 to 4.0 ± 0.4 (P < .001) immediately after completion of the curriculum. However, there was a small decrease in Critical View of Safety score after 1 year (3.2 ± 0.3 from 4.0 ± 0.4, P = .055), while still significantly higher compared to precurriculum (3.2 ± 0.3 vs 1.7 ± 0.4, P < .001). Acute care surgeons had lower Critical View of Safety retention scores compared to general surgeons (1.8 ± 0.5 vs 3.3 ± 0.4, P = .01) and minimally invasive surgeons (1.8 ± 0.5 vs 3.8 ± 0.5, P < .01). A structured curriculum helped improve practicing surgeons' attainment of obtaining the Critical View of Safety during laparoscopic cholecystectomy. However, this improvement decreased after 1 year, suggesting some decay in knowledge retention over time. Therefore, continued educational interventions on Critical View of Safety and safe laparoscopic cholecystectomy may be needed to enhance long-term retention.


High-efficiency microstructured semiconductor neutron detectors that are arrayed, dual-integrated, and stacked.
Silicon diodes with large aspect ratio 3D microstructures backfilled with 6LiF show a significant increase in neutron detection efficiency beyond that of conventional thin-film coated planar devices. Described in this work are advancements in the technology using detector stacking methods and summed-detector 6×6-element arraying methods to dramatically increase the sensitivity to thermal neutrons. The intrinsic detection efficiency of the 6×6 array for normal-incident 0.0253 eV neutrons was found 6.8% compared against a calibrated 3He proportional counter.


Nonlinear features of the superconductor-ferromagnet-superconductor φ0 Josephson junction in the ferromagnetic resonance region.
We demonstrate the manifestations of nonlinear features in magnetic dynamics and I-V characteristics of a φ0 Josephson junction in the ferromagnetic resonance region. We show that at small values of the system parameters damping, spin-orbit interaction, and Josephson-to-magnetic energy ratio, the magnetic dynamics is reduced to the dynamics of a scalar Duffing oscillator driven by the Josephson oscillations. The role of the increasing superconducting current in the resonance region is clarified. Shifting of the ferromagnetic resonant frequency and the reversal of its damping dependence due to nonlinearity are demonstrated by the full Landau-Lifshitz-Gilbert-Josephson system of equations and in its different approximations. Finally, we demonstrate the negative differential resistance in the I-V characteristics and its correlation with the fold-over effect.


The genetic code as expressed through relationships between mRNA structure and protein function.
Structured RNA elements within messenger RNA often direct or modulate the cellular production of active proteins. As reviewed here, RNA structures have been discovered that govern nearly every step in protein production: mRNA production and stability; translation initiation, elongation, and termination; protein folding; and cellular localization. Regulatory RNA elements are common within RNAs from every domain of life. This growing body of RNA-mediated mechanisms continues to reveal new ways in which mRNA structure regulates translation. We integrate examples from several different classes of RNA structure-mediated regulation to present a global perspective that suggests that the secondary and tertiary structure of RNA ultimately constitutes an additional level of the genetic code that both guides and regulates protein biosynthesis.


Transient expression of glial fibrillary acidic protein in developing oligodendrocytes in vitro.
Expression of galactocerebroside (GC) and glial fibrillary acidic protein (GFAP) was studied in oligodendrocyte-enriched cultures of newborn mouse brains. In the cultures, GC was detectable as early as 1 day in vitro (1-DIV). Using double immunofluorescence labeling, some GC-positive cells were also stained homogeneously by the anti-GFAP serum. The intensity of GFAP staining increased until 9-DIV when the GC-positive cells revealed the typical morphology of oligodendrocytes, and the GFAP staining faded thereafter. The GFAP staining pattern of the GC-positive cells was not changed upon exposure to demecolcine, even though the GC-negative, GFAP-positive astrocytes showed perinuclear aggregation of GFAP. No intermediate filaments were observed in the oligodendrocytes by electron microscopy. The results suggest that the oligodendrocytes may have soluble GFAP in a certain period of early development.


Genetic background of ochratoxin A production inPenicillium.
A part of the gene cluster responsible for the production of ochratoxin A inP. nordicum has been characterised recently. The analysed DNA region contains three putative genes: an alcaline proteinase (aspPN), a non-ribosomal peptide synthetase (npsPN) and an polyketide synthase (otapksPN). The last two genes are putative genes of the ochratoxin A biosynthetic pathway. Interestingly theotapksPN gene is present in this form only inP. nordicum but not inP. verrucosum indicating genetic differences between both ochratoxin A producingPenicillium species. The genes in ochratoxin A producingAspergillus species seems to be completely different. It has been demonstrated that thenpsPN gene is actively transcribed inP. nordicum under ochratoxin A producing conditions, indicating that this gene is involved in ochratoxin A biosynthesis.


Antarctic environment and nail growth.
Nail growth of all fingers was measured on 13 men wintering in Antarctica. A mean rate of 109-5 micrometer/day was found with the longer digits having faster growth. No significant difference was demonstrated between the warmer and colder months of the study period. Monthly variations suggested that subjects had an individual rate irrespective of environmental influences. Comparison with previous studies both in polar and temperature conditions showed growth rates in Antarctica have increased progressively; present values being comparable with observations in temperate climates.


Development of a dual specific growth rate-based fed-batch process for production of recombinant human granulocyte colony-stimulating factor in Pichia pastoris.
A number of limitations exist for production of human granulocyte colony-stimulating factor (G-CSF) in Pichia pastoris. In this study, two different specific growth rates (0.015 h-1, 0.01 h-1) were used sequentially in the mixed substrate feeding period during methanol induction phase to enhance the G-CSF titer in the culture broth. Necessary parameters required for implementing the feeding strategy, such as specific product yield on biomass (YP/X) and maintenance coefficient (m) on glycerol, methanol, and sorbitol were estimated using continuous culture technique. Using this strategy, for the same volumetric productivity, about 20% increase in protein titer was achieved over that obtained from the run carried out at a single pre-set value of 0.015 h-1 alone. Thus, implementation of higher specific growth rate (0.015 h-1) set during initial stages of the methanol induction phase followed by a lower specific growth rate (0.01 h-1) helped in achieving increased protein titers.


L-Carnitine improves mechanical responses of cardiomyocytes and restores Ca2+ homeostasis during aging.
L-Carnitine (β-hydroxy-γ-trimethylaminobutyric acid, LC) is a crucial molecule for the mitochondrial oxidation of fatty acids. It facilitates the transport of long-chain fatty acids into the mitochondrial matrix. The reduction in LC levels during the aging process has been linked to numerous cardiovascular disorders, including contractility dysfunction, and disrupted intracellular Ca2+ homeostasis. The aim of this study was to examine the effects of long-term (7 months) LC administration on cardiomyocyte contraction and intracellular Ca2+ transients ([Ca2+]i) in aging rats. Male albino Wistar rats were randomly assigned to either the control or LC-treated groups. LC (50 mg/kg body weight/day) was dissolved in distilled water and orally administered for a period of 7 months. The control group received distilled water alone. Subsequently, ventricular single cardiomyocytes were isolated, and the contractility and Ca2+ transients were recorded in aging (18 months) rats. This study demonstrates, for the first time, a novel inotropic effect of long-term LC treatment on rat ventricular cardiomyocyte contraction. LC increased cardiomyocyte cell shortening and resting sarcomere length. Furthermore, LC supplementation led to a reduction in resting [Ca2+]i level and an increase in the amplitude of [Ca2+]i transients, indicative of enhanced contraction. Consistent with these results, decay time of Ca2+ transients also decreased significantly in the LC-treated group. The long-term administration of LC may help restore the Ca2+ homeostasis altered during aging and could be used as a cardioprotective medication in cases where myocyte contractility is diminished.


A novel ENG mutation causing impaired co-translational processing of endoglin associated with hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant vascular dysplasia caused by mutations in mainly the endoglin gene (ENG) or activin-like kinase receptor 1 (ALK1) gene (ACVRL1). We investigated the molecular basis of HHT in a Japanese patient, and identified a novel missense mutation in ENG (c.38T>A, p.Leu13Gln) located in the signal peptide's hydrophobic core, but not in ACVRL1. In experiments in COS-1 cells, the Leu13Gln (L13Q) mutant endoglin appeared to be expressed as a precursor form, probably due to impaired protein processing. Flow cytometry analyses of the COS-1 cells transiently expressing recombinant endoglins revealed that the wild-type endoglin was detected on the cell surface, but the L13Q mutant was not. We also analyzed expression patterns of the recombinant endoglins by immunofluorescent staining, and found that the wild-type co-localized with the endoplasmic reticulum (ER), but the L13Q mutant did not. These results implied that the L13Q mutant endoglin fails to insert into the ER, probably due to destruction of the hydrophobic core structure in the signal peptide to be recognized by signal recognition particles. Thus, the Leu13 in the signal peptide of endoglin might be essential for correct protein processing through the ER and cell-surface expression. Taken together, the novel c.38T>A mutation in ENG would impair co-translational processing of the endoglin, and could be responsible for HHT in this patient.


Oral administration of vanadate to streptozotocin-diabetic rats restores the glucose-induced activation of liver glycogen synthase.
Isolated hepatocytes from streptozotocin-diabetic rats failed to respond to a glucose load with an activation of glycogen synthase. This lesion was associated with severely decreased activities of glycogen-synthase phosphatase and of glucokinase. All these defects were abolished after consumption for 13-18 days of drinking water containing Na3VO4 (0.7 mg/ml), and they were partially restored after 3.5 days, when the blood glucose concentration was already normalized. In all conditions the maximal extent of activation of glycogen synthase in cells closely parallelled the activity of glycogen-synthase phosphatase.


REIN: a tool at the service of the patients
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of patients' perspectives, the following key messages were retained. As shown by the SONG (Standardised Outcomes in Nephrology) initiative, the criteria for judging the dialysis treatment that patients and care-givers prefer are not those that are traditionally found in published studies. For example, for haemodialysis, they are fatigue, ability to travel, time without dialysis, impact on family and ability to work. The concern to give the patients a voice has been at the heart of the REIN registry right from the outset. In addition, there are patient representatives in the REIN Scientific Council and the Steering Group. Although mainly focused on quantitative health data collected from professionals, REIN has also supported studies pertaining to data collected directly from patients. These studies enable addressing questions pertaining to the problems faced by patients in their care pathway and their life with the disease. The setting up of a tool for routine and electronic collection of the patients' point of view in the evaluation of their treatment and the support of patient-initiated research contribute to positioning the REIN as a partner tool at the service of patients, unique in France.


PROTAC: A Novel Drug Delivery Technology for Targeting Proteins in Cancer Cells.
The treatment measures of malignant carcinomas are most important for human health. In recent years the use of targeted therapy based on small molecule compounds and identical immunoglobulin has been the most frequently used tool to combat cancerous cells. But there are still several limitations in their clinical development and applications, including their ability to bind multiple molecular target sites, both cell surface receptors and intracellular proteins, promoting a greater risk of toxicity. PROTAC is a novel technology that maintains a balance between protein synthesis and degradation and uses molecules instead of conventional enzyme inhibitors, containing two active domains and a linker to destroy unwanted selective protein (like kinase, skeleton protein and regulatory protein). PROTACs are heterobifunctional nano molecules with a size range of about 10 nanometres that eliminate the protein complexes formed by protein-protein interaction through large and flat surfaces generally defined as "undruggable" in conventional drug delivery systems, which include around 85% of proteins present in humans, suggesting their wide application in the field of drug development. Such peptide-based PROTACs have successfully shown targets' destruction in cultured cells (e.g., MetAP-2, and FKBP12F36V, receptors for estrogens and androgen). However, some obstacles prevent this technology from transferring from the laboratory to its actual clinical utility, such as delivery system and bioavailability. The scope of the presented review is to give an overview of novel PROTAC technology with its limitations, advantages, mechanism of action, and development of photocontrolled PROTACs and to summarize its futuristic approach to targeting proteins in cancer cells.


Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies.
To evaluate the cost effectiveness of on-demand treatment with esomeprazole 20mg compared with two alternative omeprazole treatment strategies for the long-term management of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis. A simple Markov model was designed to compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6 months with a strategy consisting of intermittent 4-week acute treatment courses of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole treatment (20mg once daily) following acute treatment of first relapse while on no drug treatment (a commonly used conventional care strategy). Relapse probabilities were based on pooled results from two 6-month placebo-controlled clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD without oesophagitis and on results from a GORD study with a 6-month untreated follow-up. The expected number of relapses per patient was used as the effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions were based on a UK physician survey. The cost-effectiveness analysis considered UK direct medical costs from the perspective of the National Health Service. The pooled analysis showed that after 6 months treatment, 90% of patients could control symptoms effectively with on-demand esomeprazole 20mg. The expected number of relapses per patient was estimated at 0.10 for on-demand esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for conventional omeprazole treatment. The esomeprazole strategy incurred considerably lower direct medical costs (16 to 61%) than either omeprazole strategy. On-demand treatment with esomeprazole 20mg is cost effective compared with two alternative omeprazole treatment strategies in patients with GORD without oesophagitis.


Trace element levels in the blood of workers in two steel works and a non-ferrous plant handling lead and cadmium compared with a non-exposed population.
The concentrations of 14 elements in the blood of steelworkers and industrial workers exposed to lead- and cadmium-containing dusts were measured and compared with a control group drawn from University and hospital laboratory staff. Measurements were also made of the concentrations of 20 elements in the dusts. Significantly elevated levels were observed for cadmium and lead in whole blood, but no other significant variations were noted. The concentrations of these two elements in the dusts confirmed the exposure of those groups showing high levels of cadmium and lead. High levels of iron or chromium in some of the dusts were not correlated with any changes in the mean blood levels of the exposed groups.


Temporal transcriptomic profiling of the ant-feeding assassin bug Acanthaspis cincticrus reveals a biased expression of genes associated with predation in nymphs.
Acanthaspis cincticrus (Stål) is an assassin bug with a specialized camouflaging behavior to ambush ants in the nymphal stages. In this study, we comprehensively sequenced all the life stages of A. cincticrus, including the eggs, five nymph instars, female and male adults using Illumina HiSeq technology. We obtained 176 million clean sequence reads. The assembled 84,055 unigenes were annotated and classified functionally based on protein databases. Among the unigenes, 29.03% were annotated by one or more databases, suggesting their well-conserved functions. Comparison of the gene expression profiles in the egg, nymph and adult stages revealed certain bias. Functional enrichment analysis of significantly differentially expressed genes (SDEGs) showed positive correlation with specific physiological processes within each stage, including venom, aggression, olfactory recognition as well as growth and development. Relative expression of ten SDEGs involved in predation process was validated using quantitative real-time PCR (qRT-PCR).


Reflection in Rural Family Medicine Education.
Reflection in medical education is vital for students' development as professionals. The lack of medical educators in rural family medicine can impinge on the effective reflection of residents' learning. Hence, based on qualitative research, we proposed a framework regarding reflection in rural family medicine education, indicating when, where, and how reflection is performed and progresses. The contents of reflection include clinical issues regarding knowledge and skills, professionalism in clinical decisions, and work-life balance. The settings of reflection include conference rooms, clinical wards, residents' desks, and hospital hallways. The timing of educational reflection includes during and after patient examination and discussion with various professionals, before finishing work, and during "doorknob" times (right before going back home). Rural medical teachers need competence as clinicians and medical educators to promote learning in medical residents and sustain rural medical care. Furthermore, medical teachers must communicate and collaborate with medical residents and nurses for educational reflection to take place in rural family medicine education, especially regarding professionalism. In rural family medicine education, reflection can be performed in various clinical situations through collaboration with learners and various medical professionals, aiding the enrichment of residents' learning and sustainability of rural medical care.


[Bone scintigraphy in patients with hip joint prostheses. Use of bone scintigraphy in hip pain after total hip replacement].
A retrospective investigation was undertaken to assess the value of bone scintigraphy with 99mtechnetium methylene-diphosphonate in patients referred with hip pain after total hip replacement. The material comprized 68 patients with a total of 68 prostheses. This review revealed that 10/25 of the patients with pathological scintigrams and 6/28 of the patients with normal scintigrams were submitted to replacement of the prostheses. In the way in which it was carried out and interpreted in this department, scintigraphy was of limited value in selection of the patients who required replacement of the prostheses.


Simplification of the Doppler continuity equation for calculating stenotic aortic valve area.
Determination of aortic valve area by the continuity equation is feasible and accurate but requires planimetry. Because the ratio of maximum velocities in the left ventricular outflow tract (LVOT) to aortic jet is quite similar to the ratio of velocity-time integrals at these sites, the continuity equation can be simplified by substituting maximum velocities for velocity-time integrals. Agreement with invasively determined aortic valve areas is similar with the conventional and simplified forms of the continuity equation. However, substitution of the average or sex-specific LVOT diameter for measured LVOT diameter in individual patients leads to less accurate aortic valve area determination. We conclude that simplification of the continuity equation, with measured LVOT diameter and maximum velocity and aortic jet maximum velocity, allows noninvasive calculation of the aortic valve area in a way that is simple and accurate.


Modulation of interaction of mutant TP53 and wild type BRCA1 by alkaloids: a computational approach towards targeting protein-protein interaction as a futuristic therapeutic intervention strategy for breast cancer impediment.
Protein-protein interactions (PPI) are a new emerging class of novel therapeutic targets. In order to probe these interactions, computational tools provide a convenient and quick method towards the development of therapeutics. Keeping this in view the present study was initiated to analyse interaction of tumour suppressor protein p53 (TP53) and breast cancer associated protein (BRCA1) as promising target against breast cancer. Using computational approaches such as protein-protein docking, hot spot analyses, molecular docking and molecular dynamics simulation (MDS), stepwise analyses of the interactions of the wild type and mutant TP53 with that of wild type BRCA1 and their modulation by alkaloids were done. Protein-protein docking method was used to generate both wild type and mutant complexes of TP53-BRCA1. Subsequently, the complexes were docked using sixteen different alkaloids, fulfilling ADMET and Lipinski's rule of five criteria, and were compared with that of a well-known inhibitor of PPI, namely nutlin. The alkaloid dicentrine was found to be the best docked alkaloid among all the docked alklaloids as well as that of nutlin. Furthermore, MDS analyses of both wild type and mutant complexes with the best docked alkaloid i.e. dicentrine, revealed higher stability of mutant complex than that of the wild one, in terms of average RMSD, RMSF and binding free energy, corroborating the results of docking. Results suggested more pronounced interaction of BRCA1 with mutant TP53 leading to increased expression of mutated TP53 thus showing a dominant negative gain of function and hampering wild type TP53 function leading to tumour progression.


Internal cardioversion shortens periods of postoperative atrial fibrillation: results of a prospective, multicenter trial.
Atrial fibrillation (AF) commonly occurs following open heart surgery especially in the high-risk group of old patients with reduced left ventricular function. Via Syncrus heart wires implanted on the left and right atrium internal cardioversion shocks can be applied. This prospective nonrandomized multicenter study compares duration of AF periods and clinical outcome in patients treated with Syncrus wires to a control group treated conventionally. In 88 patients Syncrus heart wires were implanted. Upon detection of AF antiarrhythmic medication was started for at least 6 hours followed by internal cardioversion. The results of this treatment were compared to a control group of 86 patients with an identical risk profile. In the Syncrus group 53.4% of patients suffered from postoperative AF compared with 50.0% in the control group. Internal cardioversion led to restoration of sinus rhythm in 60% of patients at the first series of shocks (mean energy 7.7 +/- 1.3 J) and 95.8% with the second series (mean energy 8.6 +/- 0.5 J). Length of AF periods was 12.4 +/- 7.2 hours in the Syncrus group versus 42.9 +/- 19.6 hours in control patients. Internal cardioversion using Syncrus heart wires demonstrated effectiveness in treating postoperative AF. Especially, length of AF periods could be diminished by the system with the expectation of reduction in hospital length of stay.


Anomalous metallic behaviour in the doped spin liquid candidate κ-(ET)4Hg2.89Br8.
Quantum spin liquids are exotic Mott insulators that carry extraordinary spin excitations. Therefore, when doped, they are expected to afford metallic states with unconventional magnetic excitations. Here, we report experimental results which are suggestive of a doped spin liquid with anomalous metallicity in a triangular-lattice organic conductor. The spin susceptibility is nearly perfectly scaled to that of a non-doped spin liquid insulator in spite of the metallic state. Furthermore, the charge transport that is confined in the layer at high temperatures becomes sharply deconfined on cooling, coinciding with the rapid growth of spin correlations or coherence as signified by a steep decrease in spin susceptibility. The present results substantiate the desired doped spin liquid and suggest a strange metal, in which the coherence of the underlying spin liquid promotes the deconfinement of charge from the layers while preserving the non-Fermi-liquid nature.It is expected that introducing charge carriers into an exotic quantum spin liquid state may lead to an unconventional metal but there are no clear realizations of a metallic spin liquid. Here, the authors present a spin liquid candidate that also shows evidence of strange metal behavior.


Comparison of RNA synthesis by liver nuclei from rats of various ages.
RNA synthesis was studied in nuclei isolated from male Fischer F344 rats of various ages. Both the initial rate and the extent of RNA synthesis were determined in two distinct media that result in the preferential synthesis of either mRNA or rRNA by hepatocytes. Synthesis of mRNA and rRNA, as determined by [3H]-UMP incorporation into acid-insoluble material, was shown to increase 1.6- to 3-fold from 3- to 6-months. The increase in RNA synthesis during maturation was followed by a 1.6 to 2.7-fold decrease from 6- to 31-months of age depending upon the assay medium and time of incubation. The age-related changes in RNA synthesis by rat liver nuclei were shown not to be due to changes in RNase activity, UTP uptake, or UTP degradation. RNA synthesized by liver nuclei from rats of various ages was characterized by SDS--polyacrylamide gel electrophoresis. Slight age-related differences in the size distribution of RNA isolated from liver nuclei were observed when nuclei from rats of various ages were incubated with [3H]-UTP in either assay medium.


Self-assembling crystals of an extract of Flos Sophorae Immaturus for improving the antioxidant, mechanical and barrier properties of a cassia gum film.
A novel antioxidative film was prepared by drying a film-forming solution containing the Flos Sophorae Immaturus extract (FSIE) (0-3.5%) and cassia gum (CG). Scanning electron microscopy (SEM) showed that FSIE was successfully compounded with CG. Although the addition of FSIE slightly increased the water vapor permeability (WVP) and O2 permeability (OP) of the film, it also improved its ability to block ultraviolet light significantly. The appropriate amounts of FSIE increased the tensile strength (TS) from 20.9 MPa to 30.2 MPa but reduced the elongation at break (EB) from 38.7% to 27.6%. The films doped with FSIE exhibited strong antioxidative activity and high rates of free radical scavenging. Total phenols exhibited a positive trend as the amount of FSIE increased in 50% of ethanol. The practical application of these composite films was investigated by evaluating the quality of lard wrapped in the films. After 25 d, the acid value (XAV) and peroxide value (POV) of lard packaged in CG/FSIE2% were lower than the values for lard packaged in CG/FSIE0% and plastic bag. These results showed that the CG/FSIE film had superior antioxidative activity compared to films made from plastic and pure CG.


Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.
Neurotransmitter receptors alter membrane excitability and synaptic efficacy by generating intracellular signals that ultimately change the properties of ion channels. Through expression studies in Xenopus oocytes and mammalian cells, we found that the G protein-coupled m1 muscarinic acetylcholine receptor potently suppresses a cloned delayed rectifier K+ channel through a pathway involving phospholipase C activation and direct tyrosine phosphorylation of the K+ channel. Furthermore, analysis of neuroblastoma cells revealed that a similar tyrosine kinase-dependent pathway links endogenous G protein-coupled receptors to suppression of the native RAK channel. These results suggest a novel mechanism by which neurotransmitters and hormones may regulate a specific type of K+ channel that is widely expressed in the mammalian brain and heart.


Norms for emotion-false memory lists.
False memory has been a flourishing research area for decades, and recently there has been considerable interest in how emotional content affects it. Literature reviews have noted a lack of normed materials that vary in emotional valence and arousal as a factor that contributes to the mixed findings on emotion-false memory effects. We report a pool of normed materials of this sort, the Cornell/Cortland Emotional Lists (CEL). This is a Deese/Roediger/McDermott (DRM) type list pool in which words' mean valence and arousal ratings are factorially manipulated across 32 lists. These lists' levels of mean backward associative strength (MBAS) are all high enough to induce significant levels of false memory. The lists were normed by administering them to 228 subjects at three different universities, all of whom responded to recall and recognition tests for the lists. The norming data revealed that false recall and false recognition were higher for negative lists than for positive lists, whereas true recall and true recognition were higher for positive lists than for negative lists. In addition, high arousal strengthened the valence effects on both true and false recall. These results indicate that the CEL lists are useful tozols for emotion-false memory research.


A Deep-Cycle Aqueous Zinc-Ion Battery Containing an Oxygen-Deficient Vanadium Oxide Cathode.
Rechargeable aqueous zinc-ion batteries are attractive because of their inherent safety, low cost, and high energy density. However, viable cathode materials (such as vanadium oxides) suffer from strong Coulombic ion-lattice interactions with divalent Zn2+ , thereby limiting stability when cycled at a high charge/discharge depth with high capacity. A synthetic strategy is reported for an oxygen-deficient vanadium oxide cathode in which facilitated Zn2+ reaction kinetic enhance capacity and Zn2+ pathways for high reversibility. The benefits for the robust cathode are evident in its performance metrics; the aqueous Zn battery shows an unprecedented stability over 200 cycles with a high specific capacity of approximately 400 mAh g-1 , achieving 95 % utilization of its theoretical capacity, and a long cycle life up to 2 000 cycles at a high cathode utilization efficiency of 67 %. This work opens up a new avenue for synthesis of novel cathode materials with an oxygen-deficient structure for use in advanced batteries.


Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort.
The pandemic coronavirus disease 2019 (COVID-19) has caused a high mortality rate and poses a significant threat to the population. The disease may progress with mild symptoms or may cause the need for intensive care, depending on many factors. In this study, it was aimed to determine if there is a tendency due to genetic factors in COVID-19 patients. Ninety-four of 188 patients with mild clinical and 94 with severe clinical symptoms were included in the study. The targeted panel including coagulopathy (F2, F5), viral invasion (ACE2), and inflammation (CXCL8, IFNAR2, IFNL4, IL10, IL2, IL6, IRF7, TLR3, TLR7, TNF) related genes was performed sequenced by the next generation sequencing (NGS). The variants found were classified and univariate analyses were performed to select candidate variables for logistic model. Risk factors and variants were compared. It was revealed that the presence of 2 or more risk factors caused the disease to progress severely (p < 0.001). Heterozygous IRF7:c.1357-23dup variant had a 2.5 times higher risk for mild disease compared to severe disease. Other variants were found to be more significant in mild disease. Since polymorphic variants were not evaluated in the literature, the findings of our study could not be compared with the literature. However, as variants that may be effective in the severity of infections may differ according to ethnicity. This study has the feature of being a guide for subsequent studies to be carried out especially in Turkish population. Clinical course of the COVID-19 is likely to depend on a variety of risk factors, including age, sex, clinical status, immunology and genetic factors.


1-3-7 surveillance and response approach in malaria elimination: China's practice and global adaptions.
There has been a significant reduction in malaria morbidity and mortality worldwide from 2000 to 2019. However, the incidence and mortality increased again in 2020 due to the disruption to services during the COVID-19 pandemic. Surveillance to reduce the burden of malaria, eliminate the disease and prevent its retransmission is, therefore, crucial. The 1-3-7 approach proposed by China has played an important role in eliminating malaria, which has been internationally popularized and adopted in some countries to help eliminate malaria. This review summarizes the experience and lessons of 1-3-7 approach in China and its application in other malaria-endemic countries, so as to provide references for its role in eliminating malaria and preventing retransmission. This approach needs to be tailored and adapted according to the region condition, considering the completion, timeliness and limitation of case-based reactive surveillance and response. It is very important to popularize malaria knowledge, train staff, improve the capacity of health centres and monitor high-risk groups to improve the performance in eliminating settings. After all, remaining vigilance in detecting malaria cases and optimizing surveillance and response systems are critical to achieving and sustaining malaria elimination.


Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: involvement of α2 adrenergic receptors.
Having previously observed that noradrenaline activation of β adrenergic receptors induces the synthesis of the chemokine monocyte chemoattractant protein (CCL2/MCP-1) in astrocytes, it is our interest to analyze the mechanisms involved in this process, particularly the possible effect of noradrenaline-modulating drugs. The treatment of primary rat astrocyte cultures with the noradrenaline transporter inhibitors desipramine or atomoxetine induced the expression and synthesis of CCL2/MCP-1 in these cells. This effect of both drugs in vitro suggests that CCL2/MCP-1 expression could also be modulated by some mechanism independent of the elevation of brain noradrenaline levels. This was confirmed by measuring a reduction in CCL2/MCP-1 production by the treatment with the α2 adrenergic receptor agonist clonidine. Accordingly, the blockade of α2 adrenergic receptors with yohimbine potentiated the production of MCP-1 stimulated by the activation of β receptors. While the activation of β adrenergic receptors and the subsequent elevation of cAMP levels seem to be the main pathway for noradrenaline to induce CCL2/MCP-1 in astrocytes, our data indicate that the α2 adrenergic receptors also regulate CCL2/MCP-1 expression working as inhibitory mediators.


Amino Acid Nutrition and Metabolism in Health and Disease.
Here an overview of the special issue "Amino acid nutrition and metabolism in health and disease" is given. In addition to several comprehensive and timely reviews, this issue had some original research contributions on fundamental research in animal models as well as human clinical trials exploring how the critical nutrients amino acids affect various traits.


[Posterior atlantoaxial facet screw fixation in rheumatoid arthritis].
To clarify the characteristics of the clinicopathological factors in cases of atlantoaxial instability due to rheumatoid and to introduce a new method for the treatment of this disease. Fifteen patients with atlantoaxial instability due to rheumatoid were treated with posterior facet screws to obtain immediate rigid fixation of C(1 - 2). In this series of patients, screw fixation was augmented with an interspinous C(1 - 2) strut graft which was wired in place to provide three-point stabilization and to facilitate bone fusion. In each patient fixation was satisfactory, and C(1 - 2) alignment and stability were restored without complication due to instrumentation. All patients showed osseous union (a mean follow-up period of 10 months; range 6 - 14 months). Posterior atlantoaxial facet screw fixation provides immediate three-dimension rigid fixation of C(1 - 2) that is biomechanically superior to wiring or other fixation.


Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.
Human LMNA gene mutations result in laminopathies that include Emery-Dreifuss muscular dystrophy (AD-EDMD) and Hutchinson-Gilford progeria, the premature aging syndrome (HGPS). The Lmna null (Lmna(-/-)) and progeroid LmnaΔ9 mutant mice are models for AD-EDMD and HGPS, respectively. Both animals develop severe tissue pathologies with abbreviated life spans. Like HGPS cells, Lmna(-/-) and LmnaΔ9 fibroblasts have typically misshapen nuclei. Unexpectedly, Lmna(-/-) or LmnaΔ9 mice that are also deficient for the inner nuclear membrane protein Sun1 show markedly reduced tissue pathologies and enhanced longevity. Concordantly, reduction of SUN1 overaccumulation in LMNA mutant fibroblasts and in cells derived from HGPS patients corrected nuclear defects and cellular senescence. Collectively, these findings implicate Sun1 protein accumulation as a common pathogenic event in Lmna(-/-), LmnaΔ9, and HGPS disorders.


Snakes and ladders: World development pathways' synergies and trade-offs through the lens of the Sustainable Development Goals.
This paper takes three global visions of world development to 2050 and quantifies their implications for sustainable progress employing the metrics of the Sustainable Development Goals (SDGs). The SDG outcomes are structured through the interconnectivities of the three 'wedding cake' layers of 'economy', 'society' and 'biosphere', as posited by the Stockholm Resilience Centre. The key policy contribution is to quantify the resulting SDG synergies and trade-offs, whilst also decomposing and calculating the part-worth of the market drivers which contribute to these outcomes. The paper employs a global economic simulation model that combines rational market behaviour with environmental constraints (MAGNET) and is further extended with an SDG metrics module. A 'non-sustainable' world reveals trade-offs between economy and biosphere SDGs, with population growth of particular concern to a safe planetary operating space in the world's poorest regions. Sustainable visions could reduce natural resource pressures and emissions and meet energy requirements at potentially limited economic cost. Notwithstanding, these futures do not address income inequalities and potentially increase food security concerns for the most vulnerable members of society. Consequently, developed region led international cooperation and in-kind income transfers to developing countries, constitutes a necessary prerequisite to help remedy the SDG trade-offs exhibited within the more sustainable global pathways.


Immunological effects and tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with optimized allergen/adjuvant ratio.
Subcutaneous immunotherapy (SCIT) traditionally includes an updosing phase injecting increasing doses of allergen over a period of several weeks, followed by a maintenance phase. To establish shorter and more convenient updosing schedules, a fast updosed immunologically enhanced SCIT formulation has been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio. In a randomized, controlled, parallel-group trial, patients with grass pollen induced rhinoconjunctivitis with/without asthma were treated with an immunologically enhanced SCIT formulation (AVANZ, ALK, Denmark). The trial included updosing with five injections (300, 600, 3000, 6000 and 15,000 SQ+) injected either in weekly interval (Group 1) or in 3-4 days interval (Group 2) followed by two maintenance injections (15,000 SQ+), approximately 10 weeks treatment. The immunological effects (primary endpoint) and tolerability (secondary endpoint) of the updosing schedules were evaluated. Four hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an immunological response with statistically significant increases in levels of IgE-blocking factor, IgG(4) and IgE (P < 0.001), was induced from baseline to end of trial. Most frequently reported adverse events were local injection site reactions such as injection site swellings (Group 1: 30% of patients, Group 2: 41% of patients). Other frequently reported adverse events included systemic reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to moderate allergic rhinitis and urticaria. Fast updosed immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced significant immunological effects and had an acceptable safety profile. Clinical efficacy will be investigated in future clinical trials.


Fibrogenic Potential of PW1/Peg3 Expressing Cardiac Stem Cells.
Pw1 gene expression is a marker of adult stem cells in a wide range of tissues. PW1-expressing cells are detected in the heart but are not well characterized. The authors characterized cardiac PW1-expressing cells and their cell fate potentials in normal hearts and during cardiac remodeling following myocardial infarction (MI). A human cardiac sample was obtained from a patient presenting with reduced left ventricular (LV) function following a recent MI. The authors used the PW1nLacZ+/- reporter mouse to identify, track, isolate, and characterize PW1-expressing cells in the LV myocardium in normal and ischemic conditions 7 days after complete ligature of the left anterior descending coronary artery. In both human and mouse ischemic hearts, PW1 expression was found in cells that were mainly located in the infarct and border zones. Isolated cardiac resident PW1+ cells form colonies and have the potential to differentiate into multiple cardiac and mesenchymal lineages, with preferential differentiation into fibroblast-like cells but not into cardiomyocytes. Lineage-tracing experiments revealed that PW1+ cells differentiated into fibroblasts post-MI. Although the expression of c-Kit and PW1 showed little overlap in normal hearts, a marked increase in cells coexpressing both markers was observed in ischemic hearts (0.1 ± 0.0% in control vs. 5.7 ± 1.2% in MI; p < 0.001). In contrast to the small proportion of c-Kit+/PW1- cells that showed cardiogenic potential, c-Kit+/PW1+ cells were fibrogenic. This study demonstrated the existence of a novel population of resident adult cardiac stem cells expressing PW1+ and their involvement in fibrotic remodeling after MI.


A synthesis of 3-deoxydihydrolycoricidine: refinement of a structurally minimum pancratistatin pharmacophore.
The synthesis of 3-deoxydihydrolycoricidine, a key element toward elucidation of the pancratistatin anticancer pharmacophore, is described. Biological evaluation of this compound showed it to be significantly less active against tumor cells than pancratistatin. In addition to those features previously identified, the requirement of a 2,3,4-triol functionalized ring-C is now definitely established as the minimum pharmacophoric element for potent anticancer activity.


A FeS2NPs-Luminol-MnO2NSs system based on chemiluminescence resonance energy transfer platform for sensing glutathione.
In this work, ferrous disulfide nanoparticles (FeS2NPs) with oxidase properties were synthesized, and a FeS2NPs-Luminol-MnO2 nanosheets (MnO2NSs) chemiluminescence resonance energy transfer (CRET) system was successfully established. Because of reaction with MnO2NSs, glutathione (GSH) can inhibit CRET between Luminol and MnO2NSs and recover the luminescence intensity of FeS2NPs-Luminol. Consequently, we developed a GSH sensor based on this chemiluminescence resonance energy transfer (CRET) system. Under optimal conditions, the FeS2NPs-Luminol-MnO2NSs sensing system showed very sensitive response to GSH in the range of 1 μM-500 μM. The limit of detection of GSH reached as low as 0.15 μM. Finally, the sensor was successfully used for the detection of GSH in serum.


Hiccups: an unusual manifestation of an abdominal aortic aneurysm.
A patient with hiccups was found to have an abdominal aortic aneurysm that subsequently ruptured. We believe that a leaking abdominal aortic aneurysm led to an ileus-induced distention of the splenic flexure of the colon with consequent diaphragmatic irritation and phrenic nerve stimulation. This led to persistent hiccups as a result of repetitive stimulation of the reflex arc mediating hiccups. Persistent hiccups require investigation for an underlying organic etiology, and a leaking abdominal aortic aneurysm should be included in the differential diagnosis.


Glossopharyngeal and vagoglossopharyngeal neuralgia: Long-term surgical outcomes in a single institution.
Glossopharyngeal neuralgia (GPN) and vagoglossopharyngeal neuralgia (VGPN) are infrequent syndromes that can have great negative impact on a patient's quality of life. The objective of this study is to describe the characteristics and long-term results of patients with GPN-VGPN who are treated surgically with microvascular decompression (MVD) in one institution. This is a retrospective series of 20 patients with the diagnosis of GPN-VGPN who underwent MVD. Demographic characteristics, surgical results, complications, and long-term follow-up were analyzed. The mean age of symptom onset was 51.25 years and the majority of patients were women (60%). The posterior inferior cerebellar artery was the main offending vessel (75%). The immediate MVD success rate was 100%, but during follow-up, two patients (10%) were diagnosed with VGPN and both cases presented pain recurrence. The mean follow-up was 120.4 (25-333) months. VGPN (P = 0.005) and a ≥5 day hospital stay (P = 0.032) were associated with unsuccessful outcomes. Two complications were documented, which resolved without sequelae. There was no surgical mortality. MVD is an effective and safe treatment for long-term pain relief of GPN-VGPN. VGPN and a prolonged hospital stay were associated with poor outcomes. More studies are required to confirm these findings.


Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis.
Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.


Hepatoprotective activity of Cyperus alternifolius on carbon tetrachloride-induced hepatotoxicity in rats.
The present work explored the potential hepatoprotective activity of total ethanol and successive extracts of Cyperus alternifolius L (Cyperaceae) against carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats and to isolate their bioactive constituents. For isolation and identification of the compounds, column chromatography and spectroscopic analysis were used, a model of hepatotoxicity by CCl(4) in rats was used to evaluate the total ethanol extract and its successive fractions. Phytochemical screening of C. alternifolius revealed the presence of different phytochemical groups. The plant proved to be safe for human use because it did not induce any signs of toxicity or mortality in mice when administered orally at doses up to 5000 mg kg(-1). The total alcoholic extract in doses of 100 and 200 mg kg(-1) and the successive extracts (ether, chloroform and ethyl acetate) in a dose of 10 mg kg(-1) exhibited a significant (p ≤ 0.05) protective effect by lowering the elevated serum levels of aspartate aminotransferase: 230.4, 218.8, 224.6, 227.4 and 231.6 U L(-1), respectively, compared with 111.6 U L(-1) for silymarin (25 mg kg(-1)). Serum levels of alanine aminotransferase were also reduced: 77.4, 72.7, 79.7, 76.0 and 79.7 U L(-1) compared to 63.7 U L(-1) for silymarin. Alkaline phosphatase: 164.6, 158.0, 163.6, 154.7 and 166.4 U L(-1) compared to 138.2 U L(-1) for silymarin. Total bilirubin: 0.50, 0.46, 0.55, 0.52 and 0.57 mg dl(-1) compared to 0.42 mg dl(-1) for silymarin. Cholesterol: 213.1, 200.0, 192.7, 193.6 and 197.1 mg dl(-1) compared to 180.3 mg dl(-1) for silymarin. Triglycerides: 237.3, 222.4, 209.5, 206.8 and 210.2 mg dl(-1) compared to 196.8 mg dl(-1) for silymarin. Eight phenolic compounds were isolated from C. alternifolius for the first time and identified as esculetin 1, umbelliferon 2, imperatorin 3, psoralen 4, xanthotoxin 5, quercetin 6, quercetin-3-O-rutinoside 7 and gallic acid 8. The results concluded that C. alternifolius possesses significant protective effect against hepatotoxicity induced by CCl(4).


The Synthetic and Biological Attributes of Pyrazole Derivatives: A Review.
Pyrazole nucleus is a unique structural scaffold which acts as an interesting template for combinatorial as well as medicinal chemistry. This review presents a detailed overview on the synthesis, QSAR and pharmacological applications of pyrazole. In addition, it covers most recent reports on structural modifications on pyrazole illustrating vital structural activity relationship.


Worsening Wenckebach after calcium gluconate injection: not uncommon but frequently missed diagnosis.
The objective of the study is to demonstrate a common etiology of hyperkalemia and illustrate a potential iatrogenic errors in treatment.


Polystyrene nanoparticles incorporate into the endoplasmic reticulum and disturb translation during meiotic maturation in mouse oocytes.
Polystyrene (PS) is one of the most common polymers that cause plastic pollution after release into the environment. Although a growing body of evidence has shown the adverse effects of PS on living organisms including humans, their effects on mammalian oocytes have not been extensively studied. In this study, we investigated the effect of exposure to PS-nanoparticle (PS-NPs) on meiotic maturation in mouse oocytes. We found that exogenous PS-NPs internalized into oocytes after penetrating the zona pellucida and accumulated in the cytoplasm of oocytes during meiotic maturation. Exposure to PS-NPs did not affect meiotic resumption but inhibited meiotic maturation by impairing spindle assembly and chromosome alignment. Moreover, exposure to PS-NPs increased oxidative stress and mitochondrial aggregation during meiotic maturation. Notably, internalized PS-NPs localized around the endoplasmic reticulum (ER) and disturbed translation in oocytes. Therefore, it is suggested that PS-NPs impair meiotic maturation not only by increasing oxidative stress and mitochondrial dysfunction, but also by decreasing translation efficiency after incorporating into the ER during meiotic maturation in mouse oocytes.


Coordination of the unfolded protein response during hepatic steatosis identifies CHOP as a specific regulator of hepatocyte ballooning.
The unfolded protein response (UPR) is an adaptive response that is implicated in multiple metabolic pathologies, including hepatic steatosis. In the present study, we analyzed publicly available RNAseq data to explore how the execution of the UPR is orchestrated in specimens that exhibit hepatocyte ballooning, a landmark feature of steatosis. By focusing on a panel of well-established UPR genes, we assessed how the UPR is coordinated with the whole transcriptome in specimens with or without hepatocyte ballooning. Our analyses showed that neither average levels nor correlation in expression between major UPR genes such as HSPA5 (BiP/GRP78), HSP90b1 (GRP94), or DDIT3 (CHOP) is altered in different groups. However, a panel of transcripts depending on the stringency of the analysis ranged from 16 to 372 lost its coordination with HSPA5, the major UPR chaperone, when hepatocyte ballooning occurred. In 13 genes, the majority of which is associated with metabolic processes, and the coordination with the HSPA5 was reversed from positive to negative in livers with ballooning hepatocytes. In order to examine if during ballooning, UPR genes abolish established and acquire novel functionalities, we performed gene ontology analyses. These studies showed that among the various UPR genes interrogated, only DDIT3 was not associated with conventional functions linked to endoplasmic reticulum stress during ballooning, while HSPA90b1 exhibited the highest function retention between the specimens with or without ballooning. Our results challenge conventional notions on the impact of specific genes in disease and suggest that besides abundance, the mode of coordination of UPR may be more important for disease development.


Antenatal exposure to the phenothiazines in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score.
In a prospective cohort study of 50,282 gravidas and their offspring, over-all rates of congenital malformations were similar in 1,309 children of women exposed to phenothiazine drugs during the first four lunar months of pregnancy and in 48,973 children of women who were not exposed. There was a suspicion of association between phenothiazine exposure and cardiovascular malformations. In a cohort reduced to 41,337 mother-child pairs for technical reasons, perinatal mortality rates and mean birth weight were similar according to phenothiazine exposure or nonexposure, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter the findings.


Activity of cefotaxime/desacetylcefotaxime with two aminoglycosides against gram-negative pathogens: an example of interactive synergy.
The susceptibility patterns of clinical Gram-negative isolates were determined to cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination with gentamicin (GENT) or tobramycin (TOB) by an agar dilution technique. A constant ratio of 1:1 (CTX to dCTX) was tested throughout the study. Isolates were challenged with subinhibitory levels of TOB or GENT in combination with clinically achievable levels of CTX, dCTX and CTX/dCTX to examine the interactions of the agents. Results of this study demonstrate that CTX/dCTX interacts synergistically with aminoglycosides against many Gram-negative pathogens. Synergy (defined as a fourfold or greater decrease in minimum inhibitory concentration (MIC) when CTX/dCTX was compared to CTX/dCTX/TOB) was demonstrable for 55% of isolates tested. Similarly, 45% were synergistically inhibited by CTX/dCTX/GENT. Additivism (a 2-fold decrease in MIC with the same comparisons) was evident for an additional 18 isolates for CTX/dCTX/TOB and 19 with CTX/dCTX/GENT. When data for Pseudomonas spp. were excluded from the analysis, synergy or additivism was evident with CTX/dCTX/TOB for 88% of the organisms tested and 72% with CTX/dCTX/GENT. Synergistic synergy for CTX/dCTX/TOB (an 8- to greater than 16-fold decrease in MIC for CTX) was demonstrable for 35 and 32 of 82 nonspeudomonal isolates respectively with the TOB and GENT combinations. Ninety nine percent of the nonspeudomonal isolates were inhibited by less than 4 micrograms/ml of CTX, 4 micrograms/ml of dCTX and 0.12 micrograms/ml of TOB, or 0.25 micrograms/ml of GENT, respectively.


[Stimulation of postradiation regeneration of erythropoiesis in mice with Bordetells pertussis vaccine].
Inoculation into mice of killed B. pertussis vaccine (10(10) microbial cells) one day before their sublethal irradiation (6.0 Gy) was accompanied by accelerated regeneration of erythropoiesis in the bone marrow, particularly in the spleen as was judged by the 59Fe incorporation. B. pertussis also induced an increase in endocolonization when inoculated 4-5 days after irradiation. The latter suggests a possible effect of vaccine on the hematopoietic cells, less differentiated than erythropoietin-sensitive cells (ESC), inasmuch the sensitivity of the ESC to erythropoietin commonly appeared at the later stages. When B. pertussis was inoculated into BALB/c mice one day before their infection by Rauscher's leukemia virus noticeable activation of leukemogenicity was observed. It is believed that the reason for this is the stimulation of erythroid target cells for the virus after B. pertussis vaccination. The data obtained indicate that B. pertussis vaccine activates erythropoiesis in both normal and irradiated mice.