Lysyl oxidase-mediated VEGF-induced differentiation and angiogenesis in human dental pulp cells.
To investigate the effects of recombinant human vascular endothelial growth factor (rhVEGF) on odontoblastic differentiation, in vitro angiogenesis, and expression and activity of lysyl oxidase (LOX) in human dental pulp cells (HDPCs), compared with rhFGF-2. To identify the underlying molecular mechanisms, the study focused on whether LOX was responsible for the actions of rhVEGF. Recombinant human vascular endothelial growth factor (rhVEGF) was constructed using the pBAD-HisA plasmid in Escherichia coli. HDPCs were treated with 1-50 μg mL-1 rhVEGF for 14 days. Alkaline phosphatase (ALP) activity was measured, and the formation of calcified nodules was assessed using alizarin red staining after the induction of odontogenic differentiation of HDPCs. The expression level of the odontogenic differentiation markers was detected by reverse transcription polymerase chain reaction. Signal pathways were assessed by Western blot and immunocytochemistry. The data were analysed by anova with Bonferroni's test (α = 0.05). Recombinant human vascular endothelial growth factor significantly increased cell growth (P < 0.05), ALP activity (P < 0.05) and mineralization nodule formation and upregulated the mRNA expression levels of the osteogenic/odontogenic markers that were lower with rhFGF-2. rhVEGF significantly increased amine oxidase activity (P < 0.05) and upregulated LOX and LOXL mRNA expression in HDPCs. Additionally, rhVEGF dose-dependently upregulated angiogenic gene mRNAs and capillary tube formation to a greater degree than rhFGF-2. Inhibition of LOX using β-aminopropionitrile (BAPN) and LOX or LOXL gene silencing by RNA interference attenuated rhVEGF-induced growth, ALP activity, mineralization, the expression of marker mRNAs and in vitro angiogenesis. Furthermore, treatment with rhVEGF resulted in phosphorylation of Akt, ERK, JNK and p38, and activation of NF-κB, which was inhibited by LOX or LOXL silencing and BAPN. Recombinant human vascular endothelial growth factor promoted cell growth, odontogenic potential and in vitro angiogenesis via modulation of LOX expression. These results support the concept that rhVEGF may offer therapeutic benefits in regenerative endodontics.


Eradication of superficial fungal infections by conventional and novel approaches: a comprehensive review.
During the last two decades, the occurrence of fungal infections either superficial or systemic has been increasing. Moreover, fungal infections become more difficult to treat when they show coupling with immunogenic diseases like AIDS. Superficial fungal infections are associated with skin, nail and eye and are less prominent to systemic infection. However, it may be dangerous if not treated properly. It is usually observed that conventional formulations including cream, powder, gels etc. are used to treat skin fungal infections even for the deep seated fungal infections. However, these formulations show various side-effects on the application site like burning, redness and swelling. Further, due to the immediate release of drug from these formulations they can stimulate the immune system of body generating high impact allergic reactions. Deep seated fungal infections like invasive aspergillosis and invasive candidiasis may be more difficult to treat because the drug released from conventional topical formulation can not reach at the target site due to the low penetration capacity. Similarly, in case of fungal infection of nail and eye, conventional formulations show problem of less bioavailability. Thus, to overcome the drawbacks of conventional therapy a lot of research works have been carried out to develop novel formulations of antifungal drugs to deliver them superficially. Novel formulations explored for the skin delivery of antifungal drugs include liposomes, niosomes, ethosomes, microemulsions, nanoparticles, microspheres and micelles. These formulations show extended or sustained release of drug, minimizing the side effect on application site, enhancing bioavailability and reducing the dosing frequency. Further, these formulations also show penetration into the deep skin to treat invasive fungal infections. Novel formulations explored in treatment of fungal infections of eye are liposomes and nanoparticles and whether for nail fungal infections microemulsions are the choice. In present article, we have discussed about conventional treatment of superficial fungal infection and their comparison with the novel drug delivery systems.


Implication of nitrergic system in the anticonvulsant effects of ferulic acid in pentylenetetrazole-induced seizures in male mice.
Seizures are abnormal discharge of neurons in the brain. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The present study aimed to investigate the role of the nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol (PTZ)-induced seizures in male mice. 64 male Naval Medical Research Institute (NMRI) mice weighing 25-29 g were randomly divided into eight experimental groups (n=8). FA at doses 5, 10, and 40 mg/kg alone and in combination with L-nitro-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) or L-arginine (L-arg) (nitric oxide [NO] precursor) was administrated (intraperitoneal). PTZ was injected (i.v. route) 30 min after drugs administration (1 mL/min). Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by the Griess method. FA at doses of 10 and 40 mg/kg significantly increased the seizure threshold as well as reduced the serum and brain NO levels in comparison to the saline-received group. Co-administration of the effective dose of FA (10 mg/kg) plus L-arg significantly decreased the seizure threshold in comparison to the effective dose of FA alone. Co-injection of the sub-effective dose of FA (5 mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain NO level in comparison to the sub-effective dose of FA alone. We showed that the nitrergic system, partially at least, mediated the anticonvulsant effect of FA in PTZ-induced seizures in mice. We concluded that L-NAME potentiated while L-arg attenuated the anticonvulsant effect of FA.


Plant-inspired rearrangement of liquid in a porous structure for controlled swelling.
Soft robots can adapt to dynamic environments without prior knowledge of their properties. Plants inspire mechanisms for counterbalancing dynamic loads by locally modulating compliance through anisotropic humidity-responsive materials and structures. In addition to well-known passive bilayers, plants may also actively control swelling. The combination of robust hygroscopic material-level response and simple electrical control makes active swelling particularly attractive for technological implementation. However, dynamic swelling demands the development and optimisation of congruent pumping solutions. This work suggests electrohydrodynamic pumping, enabled by highly reversible ion immobilisation at capacitive electrodes, as a particularly suitable low-pressure, high-area liquid displacement solution for active swelling. Local pore fill ratio (PFR) modulation is used as a measure for dynamic liquid displacement and swelling. A method for highly localised (10μm membrane thickness) assessment of the dynamic variation of PFR in a 400μm laminate undergoing cross-plane electrokinetic liquid displacement is developed. Two modes for transient PFR modulation were identified: electrokinetic ion transfer and diffusive solvent redistribution, pronounced at high and low voltage scan rates, respectively. The strategic combination of these modes enables various compliance-modulation scenarios. The system contains (within a cycle) a constant amount of liquid in an open network of liquid-filled pores. 30%-75% PFR yielded the highest dynamic PFR modulation: a high amount of empty pores is beneficial, yet a too-low PFR compromises the continuous liquid pathway necessary for electrokinetic pumping. The dynamic nature of internal liquid rearrangement was characterised by relatively fast electrokinetics-driven fluxes (6.3% PFR change in 80 s), followed by a slow equilibration of concentration and PFR. At high scan rates, PFR decreased at positive polarisation, while both positive and negative polarity yielded a similar decrease at low scan rates (5 mV s-1). Localised control over the swelling gradient enables the design of systems that morphologically adapt to complex dynamic loading conditions.


Spinal muscular atrophy type I and the dual role of viruses: An interview with Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School.
According to Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School and Director of the Spinal Muscular Atrophy (SMA) Program at Boston Children's Hospital in Boston (MA, USA), the diagnosis of SMA type I is clinical and is based on detailed general physical and neurological examinations. SMA type I remains the most common genetic disease resulting in death in infancy and is really devastating for the child, the parents, as well as the medical professionals with the privilege of caring for patients with SMA and their parents. The proposed management options include: i) no respiratory support; ii) non-invasive ventilation; and iii) tracheotomy with mechanical ventilation. Deciding, which option is the best, is indeed a very personal decision. The optimal clinical care should be extremely mindful of parents' wishes and management goals with regard to the quality of life. Since the end of 2016 in the USA, and recently in Europe, there exists the possibility of accessing a novel treatment drug for SMA, namely Nusinersen. This antisense oligonucleotide is administered intrathecally and increases the production of the fully functional SMN protein, thus improving motor function, the quality of life and survival. Among the ongoing clinical trials, oral treatment with RG7916, a small molecule SMN2 splicing modifier, appears to be really promising. Gene therapy using viral vectors is expected to offer an 'one and done' therapy and possibly a cure, if administered early in life, before any symptoms appear. It is really interesting that viruses, which at the moment are the cause of death of children with SMA, if genetically modified, may be used for their treatment.


Water-soluble copper(II) 5-fluorouracil complexes bearing polypyridyl co-ligands: synthesis, structures and anticancer activity.
Five newly synthesized copper(II) 5-fluorouracil (5-FU) complexes of polypyridyl co-ligands with good solubility in water, namely [CuCl(5-FU)(bpy)(DMSO)] (1), [Cu(5-FU)(phen)2](5-FU)·4H2O (2), [Cu(5-FU)(dpya)2](NO3)·2.5H2O (3), [Cu(5-FU)(NO3)(bpyma)]·H2O (4) and [CuCl(5-FU)(terpy)] (5) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dpya = 2,2'-dipyridylamine, bpyma = bis(2-pyridylmethyl)amine and terpy = 2,2';6',2''-terpyridine), were characterized by elemental analysis and a number of spectrometric methods. The structures of complexes 1-5 were determined by X-ray crystallography and the copper(II) ions were five coordinate. Cytotoxic activity of the complexes in four human cancer cell lines, A549 (lung carcinoma), MDA-MB-231 (breast carcinoma), HCT116 (colon carcinoma) and DU145 (prostate carcinoma), and a normal cell line, BEAS-2B (human lung epithelial), was determined by SRB assay and compared with that of 5-FU and cisplatin. The complexation of 5-FU together with polypyridyl ligands resulted in a significant increase in the cytotoxicity of the complexes, with complex 2 exhibiting the highest anticancer potency against all the cell lines, with HCT116 being the most sensitive. The mode of action of cell death for 2 was investigated using morphological imaging and cytometric analyses, including the capacity for induction of apoptosis, generation of reactive oxygen species, mitochondrial dysfunction and DNA damage.


High incidence and prevalence of rheumatoid arthritis in Pima Indians.
A longitudinal epidemiologic study has been conducted to estimate the incidence and prevalence of rheumatoid arthritis in an American Indian population, the Pima and Papago Indians of Arizona. Clinical, serologic, and radiologic data were collected during biennial examinations of subjects aged 20 years or more during the period 1967-1986. Rheumatoid arthritis was diagnosed by criteria for the active and the inactive disease. Age-adjusted to the 1980 US population at least 20 years of age, the prevalence of classical and definite rheumatoid arthritis in 1984 was 5.3% (3.23% in males and 6.95% in females), a rate appreciably higher than that reported in studies in Rochester, Minnesota, and in Hiroshima and Nagasaki, Japan. Among Pimas, during the study period, 70 incident cases of rheumatoid arthritis occurred. The age-adjusted incidence rate was 42.2 cases per 10,000 person-years (29.7 in males and 51.8 in females), 10.3 times as high as the age-adjusted rate in Rochester (4.1/10,000 person-years), and 5.7 times as high as in Japan (7.4/10,000 person-years). Rates generally increased with age. No secular trend was found. On the basis of both prevalence and incidence data, this study confirms that rheumatoid arthritis does not have uniform occurrence in different populations. This has to be taken into account in the search for the factors related to the differences in risk of disease.


Misinformation and work-related outcomes of healthcare community: Sequential mediation role of COVID-19 threat and psychological distress.
By applying coping theory, this study develops and tests a process model investigating the sequential mediating roles of perceived COVID-19 threat and psychological distress on the relationships between social media misinformation and turnover intentions, and in-role performance. Hypothesized model for Study 1 was fully supported, showing that the association between social media misinformation and turnover intentions are each mediated sequentially, first by perceived COVID-19 threat and then by psychological distress. Additional support was found for the sequential mediation model when predicting turnover intentions and in-role performance in Study 2, using time-lagged data. Besides, this study found that resilience moderated social media misinformation's sequential indirect effect on turnover intentions and in-role performance. Implications and future research directions have been discussed.


Rate of Rehospitalization in 60 Days of Discharge and It's Determinants in Patients with Heart Failure with Reduced Ejection Fraction in a Tertiary Care Centre in India.
Identifying the patients with acute heart failure (HF) at high risk for rehospitalization after hospital discharge will enable proper optimization of treatment. This study is aimed to evaluate the rehospitalization rate at 60 days of discharge and their predictors in patients of chronic heart failure with reduced ejection fraction (HFrEF). This prospective observational study enrolled patients with left ventricle ejection fraction (LVEF) <40%, who were admitted because of acute decompensation. Patients were followed for 60 days to analyze rehospitalization rate and its predictors. Of 103 HFrEF patients (74% male; mean age 55.8 years) enrolled, 7 patients died during index admission and 3 patients lost to follow up. The 60-day rehospitalization rate was 37% (34/93). We studied 23 clinical and 9 biochemical predictors of rehospitalization. Out of 34 events of rehospitalization, 79.41% (n=28) was due to cardiac cause followed by respiratory 5.8% (n=2), renal 5.8% (n=2) and others 5.8% (n=2). Among all the parameters, on logistic regression analysis having longer length of index hospital stay (>7 days) (52.8% vs. 28.8%; odds ratio [OR], 1.79; confidence interval [CI], 1.2-7.25; p=0.040) and chronic kidney disease (CKD) (26.5% vs. 8.5%; OR, 3.06; CI, 1.1-57.04; p=0.050) independently increased the risk of rehospitalization at 60 days of discharge. Further higher haemoglobin level (11.3 vs. 9.9 gm/dL; OR, 0.71; CI, 0.48-0.97; p=0.050) and higher LVEF at index admission (30.4% vs. 26.5%; OR, 0.87; CI, 0.75-0.99; p=0.049) were associated with decreased the risk of rehospitalization. Our study reveals that patients with HFrEF have significantly higher rehospitalization rate (37%) and in-hospital mortality rates (6.78%) of any chronic cardiac disease conditions. Correction of low hemoglobin and special care in those who are having very low LVEF, CKD and longer length of stay, including tailored therapy and frequent visits may play an important role in preventing future rehospitalization in these patients.


AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review.
Improvements in disease management, as well as endoscopic technology and quality, have dramatically changed the way in which we conceptualize and manage inflammatory bowel disease-related dysplasia over the past 20 years. Based on evolving literature, we propose a conceptual model and best practice advice statements for the prevention, detection, and management of colorectal dysplasia in people with inflammatory bowel disease. This expert review was commissioned and approved by the American Gastroenterological Association Institute Clinical Practice Updates Committee and the American Gastroenterological Association Governing Board to provide timely guidance on a topic of high clinical importance to the American Gastroenterological Association membership. It underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology.


Druggable Targets in Cytokine Release Syndromes.
Bispecific T-cell engagers and chimeric antigen receptor T cells share the problem of eliciting acute systemic inflammation episodes known as cytokine release syndrome. Knowledge on the sequential waves of cytokines that can be neutralized with clinically available agents is crucial to prevent or treat this condition without jeopardizing the antitumor therapeutic outcome. See related article by Leclercq-Cohen et al., p. 4449.


Reducing reports of illusory posttraumatic growth: A revised version of the Stress-Related Growth Scale (SRGS-R).
We evaluated a revised version of the Stress-Related Growth Scale (SRGS-R) against the original version (SRGS) and the most commonly used measure of posttraumatic growth, the Posttraumatic Growth Inventory (PTGI). The SRGS-R differs from the SRGS in that (a) the wording of each item was modified from implying positive change to neutral wording and (b) the rating scale includes both positive and negative impacts, which we believe makes the SRGS-R less prone to reports of illusory growth. Participants (N = 615) completed either the SRGS-R, the SRGS, or the PTGI, along with convergent (e.g., meaning in life), outcome (depression, anxiety, global distress, well-being, PTSD symptoms, and quality of life), and coping measures. The PTGI and the original SRGS yielded a similar pattern of results. We replicated past findings that the PTGI was unrelated to depression, anxiety, global distress, and quality of life, and positively related to PTSD symptoms. In stark contrast, the SRGS-R was significantly related to less depression, anxiety, global distress, and greater quality of life. Most notably, the SRGS-R was negatively related to PTSD symptoms. All 3 measures had acceptable associations with convergent measures and were related to use of emotion and problem-focused coping. However, the PTGI was positively related to venting and denial, whereas the SRGS-R was negatively associated with avoidance coping. Our findings suggest the SRGS-R is less prone to reports of illusory growth. Improved measurement of posttraumatic growth is vital to our understanding of how individuals grow from traumatic or stressful experiences. (PsycINFO Database Record


Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors.
The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three-dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, provide unprecedented insights in the spatial organization of genomes. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions. Our package takes as input the sequencing reads of 3C-based experiments and performs the following main tasks: (i) pre-process the reads, (ii) map the reads to a reference genome, (iii) filter and normalize the interaction data, (iv) analyze the resulting interaction matrices, (v) build 3D models of selected genomic domains, and (vi) analyze the resulting models to characterize their structural properties. To illustrate the use of TADbit, we automatically modeled 50 genomic domains from the fly genome revealing differential structural features of the previously defined chromatin colors, establishing a link between the conformation of the genome and the local chromatin composition. TADbit provides three-dimensional models built from 3C-based experiments, which are ready for visualization and for characterizing their relation to gene expression and epigenetic states. TADbit is an open-source Python library available for download from https://github.com/3DGenomes/tadbit.


Rotavirus strain distribution in Ghana pre- and post- rotavirus vaccine introduction.
Ghana introduced the monovalent rotavirus vaccine (Rotarix) into its national paediatric vaccination programme in May2012. Vaccine introduction was initiated nationwide and achieved >85% coverage within a few months. Rotavirus strain distribution pre- and post-RV vaccine introduction is reported. Stool samples were collected from diarrhoeic children <5 years of age hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains were characterized by RT-PCR and sequencing. A total of 1363 rotavirus EIA-positive samples were subjected to molecular characterization. These were made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes P[6] and P[8] constituted more than 65% of circulating G and P types in the pre-vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and G2P[6] (4.9%). During the post-vaccine period, G12, G1 and G10 genotypes, constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8] (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the emergence of the unusual rotavirus strain G9P[4] during this period. Rotavirus G1P[8], the major strain in circulation during the pre-vaccination era, was replaced by G12P[8] as the most predominant strain after vaccine introduction. This strain replacement could be temporary and unrelated to vaccine introduction since an increase in G12 was observed in countries yet to introduce the rotavirus vaccine in West Africa. A continuous surveillance programme in the post-vaccine era is necessary for the monitoring of circulating rotavirus strains and the detection of unusual/emerging genotypes.


SEXUAL FUNCTION AND IN VITRO FERTILIZATION.
The aim of the study was to investigate the sexuality of individuals undergoing in vitro fertilization as one of the methods of infertility treatment. The focus was on sexual dysfunction, sexual satisfaction and associated risk factors. Data were collected based on a validated, standardized procedure. The sample consisted of 119 individuals who had undergone in vitro fertilization, 61 (51.3%) women and 58 (48.7%) men, average age 35 years. Most of the 119 survey participants were in the 31-35 age group (37%), married (79.8%), with high school diploma (51.3%), Catholic denomination (89.9%), childless (78.2%), with a one sexual partner in their lifetime (51.3%), and in current sexual relationship for a period of 7 to 8 years (18.5%). The survey found statistically significantly higher satisfaction among male participants, participants in the 26-30 age group, those with a higher level of education, nonreligious, without children in marriage, with four sexual partners in life, over a period of 1 to 2 years in current partner (sexual) relationship, and without a diagnosed sexual disorder. There was a correlation between infertility, associated treatment, and sexuality. Infertility and involvement in treatment procedures increased the risk of sexual dysfunction. The risk factors identified in our study could help facilitate detection and timely treatment of sexual dysfunction, which would help maintain healthy sexuality in couples participating in in vitro fertilization procedures.


Serum proinsulin levels at fasting and after oral glucose load in patients with type 2 (non-insulin-dependent) diabetes mellitus.
A simple and sensitive human proinsulin radioimmunoassay system was developed using guinea pig anti-proinsulin serum, which cross-reacted neither with human insulin nor C-peptide. The recognition site of the antiserum seems to be located near the junction between the B chain and C-peptide. With this assay system, we studied the serum proinsulin concentration at fasting and after an oral 100 g glucose load in 25 healthy subjects, 21 subjects with impaired glucose tolerance and 40 patients with Type 2 (non-insulin-dependent) diabetes mellitus. At fasting, serum proinsulin was 5.8 +/- 3.3 pmol/l in normal subjects as compared to 9.5 +/- 6.9 pmol/l (p less than 0.05) in subjects with impaired glucose tolerance and 12.6 +/- 7.5 pmol/l (p less than 0.001) in diabetic patients. The molar ratio of proinsulin to insulin was also increased in subjects with impaired glucose tolerance or diabetes compared to control subjects. After a 100 g oral glucose load, serum proinsulin increased more slowly than insulin. The proinsulin response after an oral glucose load was augmented in subjects with impaired glucose tolerance and diabetes, while the insulin response decreased with the elevation of fasting plasma glucose. Diabetic patients with high fasting plasma glucose had a very poor insulin response, but the proinsulin response was similar to control subjects. There was a linear correlation between summed proinsulin values and summed insulin values, but the slope of the regression line was steeper in diabetic patients than in control subjects. There was a relative increase in serum proinsulin both in subjects with impaired glucose tolerance and diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)


The Importance of Surface-Binding Site towards Starch-Adsorptivity Level in α-Amylase: A Review on Structural Point of View.
Starch is a polymeric carbohydrate composed of glucose. As a source of energy, starch can be degraded by various amylolytic enzymes, including α-amylase. In a large-scale industry, starch processing cost is still expensive due to the requirement of high temperature during the gelatinization step. Therefore, α-amylase with raw starch digesting ability could decrease the energy cost by avoiding the high gelatinization temperature. It is known that the carbohydrate-binding module (CBM) and the surface-binding site (SBS) of α-amylase could facilitate the substrate binding to the enzyme's active site to enhance the starch digestion. These sites are a noncatalytic module, which could interact with a lengthy substrate such as insoluble starch. The major interaction between these sites and the substrate is the CH/pi-stacking interaction with the glucose ring. Several mutation studies on the Halothermothrix orenii, SusG Bacteroides thetaiotamicron, Barley, Aspergillus niger, and Saccharomycopsis fibuligera α-amylases have revealed that the stacking interaction through the aromatic residues at the SBS is essential to the starch adsorption. In this review, the SBS in various α-amylases is also presented. Therefore, based on the structural point of view, SBS is suggested as an essential site in α-amylase to increase its catalytic activity, especially towards the insoluble starch.


Spatiotemporal changes in Cx30 and Cx43 expression during neuronal differentiation of P19 EC and NT2/D1 cells.
While connexins (Cxs) are thought to be involved in differentiation, their expression and role has yet to be fully elucidated. We investigated the temporal expression of Cx30, Cx36 and Cx43 in two in vitro models of neuronal differentiation: human NT2/D1 and murine P19 cells, and the spatial localisation of Cx30 and Cx43 in these models. A temporal Cx43 downregulation was confirmed in both cell lines during RA-induced neuronal differentiation using RT-PCR (P < 0.05) preceding an increase in neuronal doublecortin protein. RT-PCR showed Cx36 was upregulated twofold in NT2/D1 cells (P < 0.05) and sixfold in P19 cells (P < 0.001) during neuronal differentiation. Cx30 exhibited a transient peak in expression midway through the timecourse of differentiation increasing threefold in NT2/D1 cells (P < 0.001) and eightfold in P19 cells (P < 0.01). Qualitative immunocytochemistry was used to examine spatiotemporal patterns of Cx protein distribution alongside neuronal differentiation markers. The temporal immunolabelling pattern was similar to that seen using RT-PCR. Cx43 was observed intracellularly and on cell surfaces, while Cx30 was seen as puncta. Spatially Cx43 was seen on doublecortin-negative cells, which may indicate Cx43 downregulation is requisite for differentiation in these models. Conversely, Cx30 puncta were observed on doublecortin-positive and -negative cells in NT2/D1 cells and examination of the Cx30 peak showed puncta also localized to nestin-positive cells, with few puncta on MAP2-positive cells. In P19 cells Cx30 was localized on clusters of cells surrounded by MAP2- and doublecortin-positive processes. The expression pattern of Cx30 indicates a role in neuronal differentiation; the nature of that role warrants future investigation.


[Cloning and functional analysis of the collectin gene from the grass carp Ctenopharyngodon idella].
The grass carp (Ctenopharyngodon idella) collectin gene was cloned from mixed liver and kidney cDNA library. The full length sequence of grass carp collectin was 1128 bp, contained a 5' untranslated region of 229 bp and a 3' untranslated region of 104 bp. The open reading frame of grass carp collectin was 795 bp which could code a 264 amino acids polypeptide, including a terminal codon. Phylogenetic analyses showed that grass carp collectin shared the highest homology with that of zebrafish (Danio rerio). To understand the function of grass carp collectin, we expressed and purified the recombinant protein (P(CRD)) that comprised carbohydrate recognition domain (CRD). Agglutination of Aeromonas hydrophila and Staphylococcus aureus etc. and sugars inhibition experiments showed that: galactose, glucose, mannose and maltose could inhibit the agglutination of Aeromonas hydrophila. Maltose could lower the agglutination of Staphylococcus aureus, whereas peptidoglycan and glucose inhibited it well. In addition, the activity of grass carp collectin could not dependent on Ca(2+).


Teaching Multilingual Students During the COVID-19 Pandemic in Austria: Teachers' Perceptions of Barriers to Distance Learning.
Providing high-quality education for students with emergent proficiency in the language of instruction (referred to here as multilingual students) presents a challenge to inclusion for educational systems the world over. In Austria, a new German language support model was implemented in the school year 2018/19 which provides language support in separate classrooms up to 20 h a week. Since its implementation, the model has been strongly criticized for excluding multilingual students from the mainstream classroom, which is argued to reinforce the educational disadvantages that they face. The study presented here provides unprecedented qualitative insight into how schooling for students within the so-called German language support classes (GLSC) was organized during the COVID-19 pandemic. It builds on results of a previous large-scale quantitative study (n = 3,400 teachers), which was conducted during the first lockdown (spring 2020) and indicated a high risk of exclusion for marginalized students, especially for multilingual students in GLSC. To gain deeper insights into the situation of these students during school closures, 37 teachers who work in these classes at both primary and lower-secondary schools in Vienna were interviewed, of which 18 interviews were considered for analysis. The interviews focus on the situation during the first and second school closures in the city of Vienna. A thematic analysis of the interview data reveals teachers' perceptions of aspects which harmed or promoted inclusion for students in GLSC during these periods of school closure. Teachers' perceptions of the most harming factors for students included strong language barriers between teachers and students, restricted access to technical equipment and supportive learning spaces, and low parental engagement. A development that promoted inclusion of these students was the option to allow them to come to school during the second school closure. Since existing studies on the schooling of students during school closures have hardly addressed the situation of students in GLSC, this study contributes to closing this research gap.


Too strong? Barriers from getting support before a suicide attempt in Lithuania.
The study aimed to understand the tendencies of help seeking before a suicide attempt in Lithuania. An analysis of interviews with 21 Lithuanian adults demonstrated strong avoidance of seeking help. The main reasons for avoidance included a lack of trust in other people, thinking that one must solve problems independently without sharing them, avoiding troubling others, and a belief that showing genuine emotions is a sign of weakness. These findings may contribute to suicide prevention by more deeply understanding the barriers to help seeking among high suicide risk groups, particularly in countries with a traumatic historical experience.


Relating empathy and emotion regulation: do deficits in empathy trigger emotion dysregulation?
Emotion regulation is a crucial skill in adulthood; its acquisition represents one of the key developmental tasks in early childhood. Difficulties with adaptive emotion regulation increase the risk of psychopathology in childhood and adulthood. This is, for instance, shown by a relation between emotion regulation and aggressive behavior in childhood age, indicating emotion dysregulation as an important risk factor of aggressive behavior and potential precursor of psychopathology. Based on (1) interrelations between emotion processes and social information processing (maladaptive emotion regulation and social information processing are associated with higher levels of aggression) and (2) recent neuroscientific findings showing that empathy deficits might not only result in difficulties labeling others' emotions but one's own emotions too, we suggest that empathy deficits might serve as potential trigger of emotion dysregulation. Different studies investigating the relation between empathy and emotion regulation are presented and discussed. Discussions are based on the assumed potential of empathy deficits triggering emotion dysregulation. Furthermore, developmental neuroscientific findings on empathy and emotion regulation are highlighted which provide further insights on how these processes might relate. Finally, possible directions for future research are presented.


[Chimeras in biologic embryology].
Chimeras produced from amphibian, mammalian, and especially avian embryos have provided important insights into vertebrate development. Important contributions have led to new concepts in understanding the development of, for example, the nervous system, the vascular system, and the skeletal muscles. The migration of cells is particularly accessible in chimeras. More important results are to be expected from chimeras in the future, especially by combining this approach with other state-of-the-art techniques.


Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.
alpha 1-Adrenergic receptor (AR) activation in cardiac muscle has several different physiological effects that might be mediated through different alpha 1-AR subtypes. Two alpha 1-AR subtypes have been cloned from the rat, the alpha 1B and the alpha 1D; both are present in adult rat heart. A third subtype, the alpha 1C, cloned from the cow and human, was reported to be absent in the rat. However, we recently found alpha 1C mRNA in adult rat heart by using a partial alpha 1C cDNA. Thus, all three cloned alpha 1-AR subtypes are present in the heart, but it is unknown whether each is expressed in cardiac myocytes or in cardiac fibroblasts. In the present study, the full-length rat alpha 1C-AR was cloned from cultured neonatal cardiac myocytes. alpha 1C mRNA transcripts of 3, 9.5, and 11 kb were present in adult rat heart by Northern blot analysis. alpha 1B-, alpha 1C-, and alpha 1D-subtype mRNAs were each present in isolated adult and neonatal cardiac myocytes by RNase protection assay. In addition, cultured neonatal cardiac myocytes expressed the three alpha 1-AR subtype mRNAs. In contrast, none of the alpha 1-AR mRNAs was detected in cultured neonatal cardiac fibroblasts. In addition, alpha 1-ARs were absent in fibroblasts by [3H]prazosin binding and norepinephrine-stimulated [3H]inositol phosphate production. The absence of alpha 1-ARs in cardiac fibroblasts differs from beta-adrenergic and angiotensin II receptors, which are present in both cardiac fibroblasts and cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Destruction of the soft palate and nose by tertiary 'benign' syphilis. A case report.
A case of untreated tertiary syphilis involving the soft palate and nose is described and the treatment is outlined. In view of the rising incidence of acquired syphilis the clinician should bear this disease in mind whenever atypical lesions are encountered.


Mechanistic studies of displacer-protein binding in chemically selective displacement systems using NMR and MD simulations.
A parallel batch screening technique was employed to identify chemically selective displacers which exhibited exclusive separation behavior for the protein pair alpha-chymotrypsin/ribonuclease A on a strong cation exchange resin. Two selective displacers, 1-(4-chlorobenzyl)piperidin-3-aminesulfate and N'1'-(4-methyl-quinolin-2-yl)-ethane-1,2-diamine dinitrate, and one non-selective displacer, spermidine, were selected as model systems to investigate the mechanism of chemically selective displacement chromatography. Saturation transfer difference (STD) NMR was used to directly evaluate displacer-protein binding. The results indicated that while binding occurred between the two chemically selective displacers and the more hydrophobic protein, alpha-chymotrypsin, no binding was observed with ribonuclease A. Further, the non-selective displacer, spermidine, was not observed to bind to either protein. Importantly, the binding event was observed to occur primarily on the aromatic portion of the selective displacers. Extensive molecular dynamic simulations of protein-displacer-water solution were also carried out. The MD results corroborated the NMR findings demonstrating that the binding of selective displacers occurred primarily on hydrophobic surface patches of alpha-chymotrypsin, while no significant long term binding to ribonuclease A was observed. The non-selective displacer did not show significant binding to either of the proteins. MD simulations also indicated that the charged amine group of the selective displacers in the bound state was primarily oriented towards the solvent, potentially facilitating their interaction with a resin surface. These results directly confirm that selective binding between a protein and displacer is the mechanism by which chemically selective displacement occurs. This opens up many possibilities for future molecular design of selective displacers for a range of applications.


A case of disseminated intravascular coagulation probably arising from sudden infant death syndrome.
The cause of death in a 45-day-old male infant who was found apneic at home and died 21 hours later was disseminated intravascular coagulation (DIC). The patient was admitted to a hospital in a state of cardio-respiratory arrest. The initial diagnosis was interrupted sudden infant death syndrome. The patient remained apneic, and recurrent discharge of bloody stool was the dominant clinical findings. He died without spontaneous respiration being restored. The autopsy revealed hemorrhages in the lungs and the ventricular septum and the free wall of the left ventricle of the heart. Microscopically, fibrin thrombi were noted in the large intestine and heart. The DIC was probably triggered by a widespread endothelial injury caused by severe hypoxia and acidosis originating from the apnea and cardiac arrest lasting longer than 30 min.


Corn starch gel for yeast cell entrapment. A view for catalysis of wine fermentation.
A new biocatalyst was prepared by immobilization of Saccharomyces cerevisiae AXAZ-1 yeast cells in the matrix of corn starch gel. This biocatalyst was used for repeated batch fermentations of glucose and grape must at various sugar concentrations (110-280 g/L) and low-temperature winemaking (5 degrees C). The biocatalyst retained its operational stability for a long period, and it was proved to be capable of producing dry and semisweet wines. The produced wines were analyzed for volatile byproducts by GC and GC-MS, and the results showed an increase in the number and amount of esters by immobilized cells. In addition, an increase in the percentages of esters and a decrease in those of alcohols with the drop of fermentation temperature were reported. The activation energy (E(a)) was lower (approximately 36%) and the reaction rate constant (k) was higher (approximately 78% at 30 degrees C and approximately 265% at 15 degrees C) in the case of immobilized cells compared to free cells, especially at low temperatures. These results show that corn starch gel may act as a promoter for the enzymes that are involved in the process or as a catalyst of the alcoholic fermentation and can explain the capability of immobilized cells for extremely low-temperature winemaking. Therefore, these results open a new way for research to find new catalysts in biotechnological processes.


Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.
The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models.


A single-source route for the synthesis of metal oxide nanoparticles using vegetable oil solvents.
We report a general method for the synthesis of metal oxide colloidal nanocrystals in sunflower oil using single-source precursors. In this research, iron oxide nanocrystals have been synthesized and characterized though this method can be extended to the synthesis of other common metal oxides such as ZnO and also to other types of vegetable oils as solvents. Using this method, nanoparticles with average diameters of 7 nm and 3 nm were obtained respectively for iron oxide and zinc oxide. The magnetic iron oxide phase was identified using powder XRD, surface enhanced Raman spectroscopy and magnetic measurements as maghemite as the main component. The magnetic measurements demonstrate the superparamagnetic behavior of the iron oxide nanoparticles. This synthetic approach is an interesting way to synthesize metal oxide nanocrystals in eco-friendly solvents of natural origin.


Molecular Interactions and Layer Stacking Dictate Covalent Organic Framework Effective Pore Size.
Interactions among ions, molecules, and confining solid surfaces are universally challenging and intriguing topics. Lacking a molecular-level understanding of such interactions in complex organic solvents perpetuates the intractable challenge of simultaneously achieving high permeance and selectivity in selectively permeable barriers. Two-dimensional covalent organic frameworks (COFs) have demonstrated ultrahigh permeance, high selectivity, and stability in organic solvents. Using reactive force field molecular dynamics modeling and direct experimental comparisons of an imine-linked carboxylated COF (C-COF), we demonstrate that unprecedented organic solvent nanofiltration separation performance can be accomplished by the well-aligned, highly crystalline pores. Furthermore, we show that the effective, as opposed to designed, pore size and solvated solute radii can change dramatically with the solvent environment, providing insights into complex molecular interactions and enabling future application-specific material design and synthesis.


Nitrogen starvation-induced cellular crosstalk of ROS-scavenging antioxidants and phytohormone enhanced the biofuel potential of green microalga Acutodesmus dimorphus.
Microalgae accumulate a considerable amount of lipids and carbohydrate under nutrient-deficient conditions, which makes them one of the promising sustainable resources for biofuel production. In the present study, to obtain the biomass with higher lipid and carbohydrate contents, we implemented a short-term nitrogen starvation of 1, 2, and 3 days in a green microalga Acutodesmus dimorphus. Few recent reports suggest that oxidative stress-tolerant microalgae are highly efficient for biofuel production. To study the role of oxidative stress due to nitrogen deficiency, responses of various stress biomarkers like reactive oxygen species (ROS), cellular enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and non-enzymatic scavengers proline and polyphenols were also evaluated. Further, the endogenous levels of phytohormones abscisic acid (ABA) and indole-3-acetic acid (IAA) were also determined to study their response to nitrogen deficiency. We observed that nitrogen starvation of 2 days is effective to produce biomass containing 29.92% of lipid (comprising about 75% of neutral lipid) and 34.80% of carbohydrate, which is significantly higher (about 23 and 64%, respectively) than that of the control culture. Among all nitrogen-starved cultures, the accumulations of ROS were lower in 2 days starved culture, which can be linked with the several folds higher activities of SOD and CAT in this culture. The accumulations of proline and total polyphenols were also significantly higher (about 4.7- and 1.7-folds, respectively, than that of the control) in 2 days nitrogen-starved culture. The levels of phytohormones once decreased significantly after 1 day, increased continuously up to 3 days of nitrogen starvation. The findings of the present study highlight the interaction of nitrogen starvation-induced oxidative stress with the signaling involved in the growth and development of microalga. The study presents a comprehensive picture of the adaptive mechanisms of the cells from a physiological perspective along with providing the strategy to improve the biofuel potential of A. dimorphus through a short-term nitrogen starvation.


The Decline and Fall of Materia Medica and the Rise of Pharmacology and Therapeutics in Veterinary Medicine.
Materia Medica is a Latin term, relating to the history of pharmacy. It describes the sources (vegetable, animal and mineral), nature, preparation, and properties of substances or mixtures of substances, which were used as remedies for the treatment of diseases. Bourgelat authored the first veterinary Materia Medica book. This review describes the evolution and ultimate downfall of Materia Medica concepts and practices. Its survival for more than two millennia reflected the impact of religion and dogmas on therapy. The consignment of Materia Medica to history was signified by publication of the first modern book of veterinary pharmacology and therapeutics by Meyer Jones in 1953. Previously, the dominance of Materia Medica was linked to an hippiatry culture, which was shared with farriers and quacks. The Pasteurian and pharmacological revolutions of the second half of the nineteenth century led to its gradual abandonment. This review explains why the existence of authentically active substances, such as opioid analgesics, cardiotonics and general anesthetics either were not used for those actions or were badly prescribed, in part because of historical precedence and in part from lack of pathophysiological knowledge to justify rational use. The modern concept of dosage, in particular inter-species differences, was not understood. There were also major dogmas, supporting false indications, such as failure to recognize pain as a symptom to be treated, whereas inflammation was only a disease symptom involving excess of activity of the blood system, which had to be vigorously addressed by bleeding and purging. This review covers a well-defined period, ranging from Bourgelat, who wrote the first book of Materia Medica for veterinary studies to the first edition of Meyer Jones textbook in 1953, which marked the end of Materia Medica and the beginning of pharmacology in veterinary medicine.


Mindset shift on PJ paralysis.
When I first created #EndPJparalysis, little did I know it would be adopted globally - and particularly across the UK - as a vehicle for enabling patients to get up, dressed and moving while in hospital.


Accumulated Epinephrine Dose is Associated With Acute Kidney Injury Following Resuscitation in Adult Cardiac Arrest Patients.
The goal of this study was to investigate the association between total epinephrine dosage during resuscitation and acute kidney injury after return of spontaneous circulation in patients with cardiac arrest. We performed a secondary analysis of previously published data on the resuscitation of cardiac arrest patients. Bivariate, multivariate logistic regression, and subgroup analyses were conducted to investigate the association between total epinephrine dosage during resuscitation and acute kidney injury after return of spontaneous circulation. A total of 312 eligible patients were included. The mean age of the patients was 60.8 ± 15.2 years. More than half of the patients were male (73.4%) and had an out-of-hospital cardiac arrest (61.9%). During resuscitation, 125, 81, and 106 patients received ≤2, 3 - 4, and ≥5 mg epinephrine, respectively. After return of spontaneous circulation, there were 165 patients (52.9%) and 147 patients (47.1%) with and without acute kidney injury, respectively. Both bivariate and multivariate analysis showed a statistically significant association between total epinephrine dosage and acute kidney injury. The subgroup analysis showed that the strength of the association between epinephrine dosage and acute kidney injury varied by location of cardiac arrest. Further multivariate regression analysis found that the association between epinephrine dosage and acute kidney injury was only observed in patients with in-hospital cardiac arrest after adjusting for multiple confounding factors. Compared with in-hospital cardiac arrest patients who received ≤2 mg of epinephrine, patients with 3-4 mg of epinephrine or ≥5 mg of epinephrine had adjusted odds ratios of 4.2 (95% confidence interval 1.0-18.4) and 11.3 (95% confidence interval 2.0-63.0), respectively, to develop acute kidney injury. Therefore, we concluded that a higher epinephrine dosage during resuscitation was associated with an increased incidence of acute kidney injury after return of spontaneous circulation in adult patients with in-hospital cardiac arrest.


The Relationship Between Non-HDL-C /HDL-C Ratio (NHHR) and Vitamin D in Type 2 Diabetes Mellitus.
The objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM). This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups. NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P<0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P<0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference. For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM.


According to Revised EWGSOP Sarcopenia Consensus Cut-Off Points, Low Physical Function Is Associated With Nutritional Status and Quality of Life in Maintenance Hemodialysis Patients.
The aim of this study is to assess the association of nutritional status and quality of life with low physical function, according to the revised European Working Group on Sarcopenia in Older People (EWGSOP) - sarcopenia consensus cut-offs in maintenance hemodialysis patients. This is a cross-sectional study including patients on maintenance hemodialysis. Participants were submitted to a single evaluation of physical function, nutritional status, and quality of life. Handgrip strength, Short Physical Performance Battery (SPPB), sit-to-stand test, and gait speed were performed to evaluate physical function. Cut-offs proposed by the revised EWGSOP consensus were considered. Malnutrition Inflammation Score was used to assess nutritional status. Quality of life was assessed by the 36-Item Short Form Health Survey. Seventy-seven patients were enrolled, 64.9% male, mean age 55 ± 14 years. According to the cut-offs proposed by the most recent EWGSOP consensus, 55.8% of patients presented SPPB <8, 48.1% gait speed test ≤0.8 m/seconds, sit-to-stand test >15 seconds, and 39.0% handgrip strength <27 kg and <16 kg for men and women, respectively. Malnutrition Inflammation Score was significantly associated with all physical function parameters, except gait speed, in receiver operating characteristic curve and logistic regression. The 36-Item Short Form Health Survey domains or component summary were associated with SSPB, gait speed, and handgrip strength in logistic regression. Poor nutritional status and quality of life are associated with low physical function (according to the cut-offs proposed by EWGSOP) in hemodialysis patients.


The Impact of Comorbidities on the Outcomes of Egyptian COVID-19 Patients: A Follow-Up Study.
This study evaluated the clinical manifestation of COVID-19 and adverse outcomes in patients with comorbidities (outcome: death). A comparative follow-up investigation involving 148 confirmed cases of COVID-19 was performed for a month (between April and May 2020) at Qaha Hospital to describe the clinical characteristics and outcomes resulting from comorbidities. Participants were divided into two clusters based on the presence of comorbidities. Group I comprised cases with comorbidities, and Group II included subjects without comorbidity. Survival distributions were outlined for the group with comorbidities after the follow-up period. Fever (74.3%), headache (78.4%), cough (78.4%), sore throat (78.4%), fatigue (78.4%), and shortness of breath (86.5%) were the most prevalent symptoms observed in COVID-19 patients with comorbidities. Such patients also suffered from acute respiratory distress syndrome (37.8%) and pneumonia three times more than patients without comorbidities. The survival distributions were statistically significant (chi-square = 26.06, p ≤ 0.001). Multiple comorbidities in COVID-19 patients are linked to severe clinical symptoms, disease complications, and critical disease progression. The presence of one or more comorbidities worsened the survival rate of patients.


Prevalence of GBV-C/HGV, a novel 'hepatitis' virus, in patients with aplastic anaemia.
GBV-C or hepatitis G virus (GBV-C/HGV) is a novel RNA virus with similarities to members of the Flaviviridae family, especially hepatitis C. Viral RNA is detected in about 1.5% of American blood donors, with higher prevalence in multiply transfused patients and in individuals with hepatitis or liver disease. Some cases of aplastic anaemia follow apparent non-A, non-B, non-C viral hepatitis, and GBV-C viraemia has been described in three case reports of hepatitis-associated aplastic anaemia. We tested clinical samples from patients with aplastic anaemia with or without recent hepatitis for the presence of GBV-C/HGV. Virus was detected in a total of 15/57 (26.3%) of patients with aplastic anaemia and 12/52 (23.1%) of multiply transfused control patients. Sequencing of the 188 base pair NS3 helicase PCR product in the serum of five individuals indicated the same high degree of sequence variation as has been seen among other isolates of the virus. GBV-C/HGV does not appear to be implicated in the aetiology of aplastic anaemia.


[Are desquamated trophoblastic cells retrieved from the cervix suitable for a prenatal diagnosis?].
Prenatal diagnosis based on sampling of fetal tissues, amniotic fluid or chorionic villi is associated with the risk of miscarriage and fetal damage. These risks would be avoided if diagnosis could be performed in desquamated trophoblast cells recovered non-invasively from the maternal cervix. We report on our experience of fetal karyotyping on endocervical lavage using in situ hybridization (FISH) and DNA amplification (PCR) fetal sex was correctly predicted in 8/10 cases by FISH and in 6/10 by PCR. FISH appeared to be a reliable technique for karyotyping when trophoblast can be recovered from the maternal endocervix (8/10).


Patient-reported extremity symptoms after robot-assisted laparoscopic cystectomy.
To describe patient-reported extremity symptoms after robot-assisted laparoscopic cystectomy in patients with bladder cancer. Preventive activities for remaining patient safety due to correct positioning play an important part in perioperative nursing care.Extremity injuries are well-known after prolonged surgery, especially in robot-assisted urologic surgery in the steep Trendelenburg position. The risk of injury increases due to patient-related and operative risk factors. A quantitative prospective observational study was conducted. Patients were followed up with the QuickDASH (Disabilities in the Arm, Shoulder and Hand), Lower Extremity Functional Scale (LEFS) and a study-specific questionnaire 7-10 days and monthly, up to six months after surgery in patients with extremity symptoms. The study adheres to STROBE (strengthening the reporting of observational studies in epidemiology) guidelines, see Supporting information File S1. Out of the 94 included participants, 46.8% (n = 44) experienced extremity symptoms 7-10 days after surgery. Pain, numbness and weakness were the most frequent symptoms. There was a discrepancy between the patients reported symptoms and the documentation in the patient records. Only 13.6% (n = 3) of the reported pain was documented, respectively 27.5% (n = 11) of other symptoms. A large proportion of the patients report postoperative extremity symptoms after robot-assisted laparoscopic cystectomy. Prevention of complications in the perioperative setting, are together with follow-ups, important nursing activities for maintaining patient safety and may both prevent and detect postoperative extremity symptoms and injuries. This study reveals the need of accurate documentation regarding extremity symptoms in digital patient records, as well as continuous follow-ups during the hospital stay and after hospital discharge to enable detection of treatable extremity injuries. The result of this study also indicates the importance of nursing activities such as evidence-based positioning guidelines in the operating theatre for optimal positioning.


Constructing a collagen hydrogel for the delivery of stem cell-loaded chitosan microspheres.
Multipotent stem cells have been shown to be extremely useful in the field of regenerative medicine. However, in order to use these cells effectively for tissue regeneration, a number of variables must be taken into account. These variables include: the total volume and surface area of the implantation site, the mechanical properties of the tissue and the tissue microenvironment, which includes the amount of vascularization and the components of the extracellular matrix. Therefore, the materials being used to deliver these cells must be biocompatible with a defined chemical composition while maintaining a mechanical strength that mimics the host tissue. These materials must also be permeable to oxygen and nutrients to provide a favorable microenvironment for cells to attach and proliferate. Chitosan, a cationic polysaccharide with excellent biocompatibility, can be easily chemically modified and has a high affinity to bind with in vivo macromolecules. Chitosan mimics the glycosaminoglycan portion of the extracellular matrix, enabling it to function as a substrate for cell adhesion, migration and proliferation. In this study we utilize chitosan in the form of microspheres to deliver adipose-derived stem cells (ASC) into a collagen based three-dimensional scaffold. An ideal cell-to-microsphere ratio was determined with respect to incubation time and cell density to achieve maximum number of cells that could be loaded. Once ASC are seeded onto the chitosan microspheres (CSM), they are embedded in a collagen scaffold and can be maintained in culture for extended periods. In summary, this study provides a method to precisely deliver stem cells within a three dimensional biomaterial scaffold.


Myopic Shift after Implantation of a Novel Diffractive Trifocal Intraocular Lens in Korean Eyes.
To evaluate the clinical outcomes of cataract surgery using novel diffractive trifocal intraocular lenses (IOLs) in Koreans. This was a retrospective, consecutive, interventional study of cataract surgery using POD FineVision IOL implantation. Complete ophthalmologic examinations were performed preoperatively and postoperatively. Defocus curves were assessed over a range of +1.5 to -4.0 diopters in 0.5-diopter steps at one month postoperatively. Uncorrected distant visual acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity, corrected distant visual acuity, distant-corrected intermediate visual acuity, and distant-corrected near visual acuity were assessed one month postoperatively, and manifest refraction was performed during every visit. The study analyzed 31 eyes in 20 patients. There were statistically significant improvements in uncorrected distance visual acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity, corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity (p < 0.001). The final postoperative refractive outcomes showed statistically significant myopic shifts compared to the target refraction based on SRK/T, SRK-II, Haigis, and Hoffer Q formulas (p < 0.001). POD FineVision IOLs provide stable visual restoration with improvements of near and intermediate vision in presbyopic eyes. POD FineVision IOLs show myopic shift in a Korean population; therefore, surgeons should be cautious when selecting IOL power in such patients.


Breast feeding and formula feeding affect differently plasma thyroid hormone concentrations in infant baboons.
We tested the hypothesis that plasma thyroid hormone levels in infant baboons are differentially affected by breast-feeding and nursery rearing. Infant baboons were breast-fed (n = 17), or fed formulas with a high polyunsaturated to saturated fat ratio (P/S) (n = 13), or a low P/S formula (n = 14). Plasma total triiodothyronine (T3) and free T3 (fT3) concentrations increased from 4 to 14 weeks of age in infants fed either formula, but decreased in breast-fed infants. At 9 and 14 weeks of age, infants fed the formulas averaged 31% higher T3 and 53% higher fT3 concentrations compared with breast-fed infants. Although T3 concentrations of the high P/S formula group compared with the low P/S formula group were not different at any single age, from 4 to 14 weeks the T3 averaged 19% higher in the high P/S formula group. Plasma total thyroxine (T4) or free T4 (fT4) concentrations were not significantly different among the diet groups during the preweaning period. In summary, formula-fed infants maintained higher plasma T3 and fT3 levels compared with breast-fed infants in the late preweaning period.


Differential microRNA epression in asthma and the role of miR-1248 in regulation of IL-5.
Asthma is a chronic inflammatory disease that can be difficult to manage due to a lack of diagnostic biomarkers and an incomplete understanding of the molecular pathogenesis. MicroRNAs (miRNAs) are small, single-stranded, non-coding RNAs with increasing importance in regulation of immune function and as biomarkers. We profiled miRNAs in the serum of asthmatics and non-asthmatic controls to identify miRNAs that could serve as diagnostic markers and potential regulators of allergic inflammation. Differential expression of miR-1248, miR-26a, Let-7a, and Let-7d were observed in asthmatic patients compared to controls. Predictive algorithm analyses of these miRNAs revealed their specificity for different Th2 cytokines, including IL-5, which has not previously been shown to be post-transcriptionally regulated. Using multiple approaches, we showed that miR-1248 physically interacts with the IL-5 transcript in the 3' untranslated region and serves as a positive regulator to increase IL-5 expression. Collectively, our results demonstrate a previously uncharacterized mode of regulation of IL-5 expression and potential use for miRNAs in the diagnosis and clinical management of asthma.


Plantar pressures, plantar forces, and their influence on the pathogenesis of diabetic foot ulcers: a review.
Clinical recommendations for the prevention and healing of diabetic foot ulcers (DFUs) are somewhat clear. However, assessment and quantification of the mechanical stress responsible for DFU remain complex. Different pressure variables have been described in the literature to better understand plantar tissue stress exposure. This article reviews the role of pressure and shear forces in the pathogenesis of plantar DFU. We performed systematic searches of the PubMed and Embase databases, completed by a manual search of the selected studies. From 535 potentially relevant references, 70 studies were included in the full-text review. Variables of plantar mechanical stress relate to vertical pressure, shear stress, and temporality of loading. At this time, in-shoe peak plantar pressure (PPP) is the only reliable variable that can be used to prevent DFU. Although it is a poor predictor of in-shoe PPP, barefoot PPP seems complementary and may be more suitable when evaluating patients with diabetes mellitus and peripheral neuropathy who seem noncompliant with footwear. An in-shoe PPP threshold value of 200 kPa has been suggested to prevent DFU. Other variables, such as peak pressure gradient and peak maximal subsurface shear stress and its depth, seem to be of additional utility. To better assess the at-risk foot and to prevent ulceration, the practitioner should integrate quantitative models of dynamic foot plantar pressures, such as in-shoe and barefoot PPPs, with the regular clinical screening examination. Prospective studies are needed to evaluate causality between other variables of mechanical stress and DFUs.


Physical and chemical properties of edamame during bean development and application of spectroscopy-based machine learning methods to predict optimal harvest time.
This study aims to investigate the changes in physical and chemical properties of edamame during bean development and apply a spectroscopy-based machine learning (ML) technique to determine optimal harvest time. The edamame harvested at R5 (beginning seed), R6 (full seed), and R7 (beginning maturity) growth stages were characterized for physical and chemical properties, and pods were measured for spectral reflectance (360-740 nm) using a handheld spectrophotometer. The samples were categorized into 'early', 'ready', and 'late' based on the characterized properties. The results showed that pod/bean weight and pod thickness peaked at R6 and remained stable thereafter. Sugar, starch, alanine, and glycine also peaked at R6 but proceeded to decline. The ML method (random forest classification) using pods' spectral reflectance had a high accuracy of 0.95 for classifying 'early' and 'late' samples and 0.87 for classifying 'early' and 'ready' samples. Therefore, this method can determine the optimal harvest time of edamame.


[Right infectious endocarditis. Study of 30 cases].
Due to the lack of specificity of the clinical picture in the right-sided infective endocarditis, the correct diagnosis is rarely made. We reviewed 30 cases with right-sided or right and left infective endocarditis, treated in the INC from 1946 to 1982. The average age was 20 years. Rheumatic fever (53%), congenital heart disease (40%) and cardiac prostheses (7%) were the more common underlying diseases. The diagnosis was made on an average 7.3 months after the first symptom. Heart failure (93%), fever (76%), weight loss (73%), haemoptysis (66%) and general malaise (53%) were the predominant symptoms. There was no diagnostic suspicion in 9 patients (30%) and in 7 from 16 with negative blood culture, the infection was exclusively right-sided. Peripheral and pulmonary embolism was the most frequent complication. (66%) There were 29 deaths (96.6%). In all of them the diagnosis was confirmed in the postmortem examination. Heart failure and septic shock were the main causes of death. Almost all patients were infected with gram-negative germs and staphylococcus Aureus. This diagnosis should be suspected in a patient with known heart disease, who develops unexplained heart failure, moreover if pulmonary emboli are a feature. The diversity of the isolated germs is different from other publication that have shown staphylococcus as the most prevalent microorganism. This difference can be explained by the lack of drug abuse in our cases. The mortality rate is higher than in the left sided endocarditis.


Portrayal of neurological illness and physicians in the works of shakespeare.
William Shakespeare was arguably one of the most prolific writers of all time. The topics explored in his works include both physicians and neurological illnesses. In addition to a review of the portrayal of neurological diseases such as dementia, epilepsy, parkinsonism, and parasomnias, this article describes the roles of physicians in Shakespeare's plays. Furthermore, a novel hypothesis that King Lear, one of Shakespeare's more tragic figures, suffered from dementia with Lewy bodies is explored based on evidence from the dialogue of the drama.


Self-adhesive resin cements—part I.
A recent Medline search revealed 214 publications related to the search term "self-adhesive resin cements." The Journal published a Critical Appraisal on these materials by Burgess and colleagues in late 2010 (J Esthet Restor Dent 2010;22:412-9). One hundred fifty-eight of those were published in 2009 or later, so the knowledge base on this subject is growing rapidly. With that in mind, we thought it would be helpful to provide an update. The update will be presented in two parts. Here in Part I, the specific topics addressed are bonding to tooth structure, bonding to zirconia ceramics, and effects of curing mode.


Clinical Manifestation of Cytomegalovirus-Associated Protein-Losing Enteropathy in Children.
In children, CMV-associated protein-losing enteropathy (PLE) is characterised by a benign course and spontaneous healing but can lead to generalised oedema. Poorly defined, it is diagnosed after unnecessary invasive tests. Children with CMV-associated PLE between 2009 and 2019 in two French hospitals are retrospectively described. Clinical and biological signs, CMV identification, endoscopy and histological findings, disease management and course are analysed. CMV-associated PLE is proven in 21 immunocompetent and 22 immunosuppressed patients, with ages consistent with primo-infection and reactivation, respectively. The digestive symptoms prevail in immunocompetent children, mainly with vomiting (85.7% versus 50%, CI [1.2; 39.2], p = 0.02). Immunocompetent patients show more oedema (61.9% versus 4.5%, CI [3.6; 1502.4], p < 0.001), linked to more severe hypoalbuminemia (21.2 g/L [17.6-25.7] versus 29.6 g/L [24.9-33.9], p = 0.01). A severe course is observed in 23.8% of the immunocompetent patients and 54.5% of the immunosuppressed ones (p = 0.06). Evidence of CMV infection based on non-invasive methods is found on 88.9% of immunocompetent and 95.5% of immunosuppressed patients (p = 0.58), while endoscopy was performed on 95.2% and 100% of them, respectively (p = 0.48), without any therapeutic change. Thus, CMV-associated PLE should be suspected in children with generalised oedema. Not as benign as previously described, it can be confirmed using non-invasive tests.


[Association of age-related hearing loss with mice which expressed only one copy of gene encoding NKCC1 co-transporter].
To generate transgenic mice of NKCC1 +/- (heterozygous) and NKCC1 +/+ (wild-type) that have a targeted disruption in the NKCC1 gene in order to investigate the relationship of one copy of NKCC1 gene (NKCC1 +/-) and age-related hearing loss (AHL) and to study the possible pathogenesis of AHL METHODS: Auditory function of NKCC1 +/- mice was detected regularly by auditory brain response (ABR) and endocochlear potential (EP). Morphology of cochlea was observed by scanning electron microscope and content of NKCC1 protein was detected by Western blot. The mean value for ABR thresholds was elevated in NKCC1 +/- mice more than that of NKCC1 +/+ mice (P < 0.01). A progression of age-related hearing loss was found in NKCC1 +/- mice. Compared with younger NKCC1 +/- mice, the mean value for ABR thresholds in aged NKCC1 +/- mice was significantly increased (P < 0.05). The EP of NKCC1 +/- aged mice was also significantly decreased more than that of the younger NKCC1 +/+ mice (P < 0.05). And content of NKCC1 protein were reduced with the growth of the age. The scanning electron microscope showed a kind of scattered punctiform absence of outer hair cells in elder NKCC1 +/- mice cochlea. NKCC1 gene maybe takes part in the pathogenesis of AHL. Mice that expressed only one copy of NKCC1 could lead to AHL. AHL may be correlative with the amounts of NKCC1 protein and its function and also with the loss of outer hair cells perhaps.


Nutritional value of human milk.
Breast milk is the food most suited for the normal newborn infant. The evolution, complexity and general nutrient composition of this biological fluid is discussed from the perspective of the normal infant's requirements for growth and current knowledge of neonatal nutritional requirements.


A woman with three ectopic pregnancies after in-vitro fertilization and embryo transfer.
Although a higher incidence of ectopic pregnancy has been reported after in-vitro fertilization (IVF) and embryo transfer, three ectopic pregnancies in the same woman is very rare. A patient of 32 years underwent IVF-embryo transfer six times within 3 years. Three of four conceptions resulted in ectopic pregnancies. The first involved simultaneous intrauterine and left tubal pregnancy, the second was a right tubal pregnancy, and the third was a right interstitial pregnancy. In IVF-embryo transfer, bilateral salpingectomy does not remove the risk of interstitial or cornual pregnancy.


The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.
To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.


Mycotoxin fumonisin B1 increases intestinal colonization by pathogenic Escherichia coli in pigs.
Fumonisin B(1) (FB(1)) is a mycotoxin that commonly occurs in maize. FB(1) causes a variety of toxic effects in different animal species and has been implicated as a contributing factor of esophageal cancers in humans. In the present study, we examined the effect of dietary exposure to FB(1) on intestinal colonization by pathogenic Escherichia coli associated with extraintestinal infection. Three-week-old weaned pigs were given FB(1) by gavage as a crude extract or as a purified toxin at a dose of 0.5 mg/kg of body weight daily for 6 days. On the last day of the toxin treatment, the pigs were orally inoculated with an extraintestinal pathogenic E. coli strain. All animals were euthanized 24 h later, necropsies were performed, and tissues were taken for bacterial counts and light microscopic examination. Ingestion of FB(1) had only a minimal effect on animal weight gain, did not cause any macroscopic or microscopic lesions, and did not change the plasma biochemical profile. However, colonization of the small and large intestines by an extraintestinal pathogenic E. coli strain was significantly increased. Our results show that FB(1) is a predisposing factor to infectious disease and that the pig can be used as a model for the study of the consequences of ingesting mycotoxin-contaminated food.


Histidine-containing peptide catalysts developed by a facile library screening method.
Although peptide catalysts have a high potential for the use as organocatalysts, the optimization of peptide sequences is laborious and time-consuming. To address this issue, a facile screening method for finding efficient aminocatalysts from a peptide library has been developed. In the screening for the Michael addition of a malonate to an enal, a dye-labeled product is immobilized on resin-bound peptides through reductive amination to visualize active catalysts. This procedure allows for the monitoring of the reactivity of entire peptides without modifying the resin beads beforehand. Peptides containing histidine at an appropriate position were identified by this method. A novel function of the histidyl residue, which enhances the binding of a substrate to the catalyst by capturing an iminium intermediate, was indicated.


Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency.
Gyrate atrophy (GA) is an autosomal recessive eye disease characterized by progressive loss of vision due to chorioretinal degeneration. It is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase (OATase) with consequent hyperornithinemia. Although the clinical phenotype is largely confined to the eye, OATase deficiency is a systemic disorder. A step toward delineation of the enzyme defect in GA at the molecular level has been made by cloning and characterizing the cDNA and structural gene for OATase. The structural gene for OATase maps to chromosome 10 (10q26) and OATase-related sequences map to the X chromosome (Xp11.2). A diverse number of mutations at the OATase locus in GA patients of varied ethnic origins have been defined employing polymerase chain reaction and other molecular biological techniques. The majority of these mutations are of the missense type although a splicing mutation in one patient has recently been identified. The functional consequences of some of these mutations have been tested and confirmed in a eukaryotic expression system. These mutations demonstrate the allelic heterogeneity, which extends to both pyridoxine responsive and non-responsive forms of GA, reflecting the clinical and biochemical heterogeneity observed in this disease. The molecular studies in addition to providing information on the structure/function of the enzyme will facilitate understanding of the retinal pathophysiology in this disorder.


Cyclooxygenase-2 expression is positively associated with lymph node metastasis in nasopharyngeal carcinoma.
Accumulating evidence has demonstrated that cyclooxygenase-2 (COX-2) is involved in head and neck cancers, especially in nasopharyngeal carcinoma (NPC). However, the association between COX-2 expression and lymph node metastasis in NPC remains uncertain. This systematic review and meta-analysis meta-analysis investigated the relationship between COX-2 expression and lymph node metastasis and other signs of disease progression in NPC. Previously published studies assessing COX-2 expression and lymph node metastasis in NPC were identified in four English databases and three Chinese ones (Pubmed, Embase, Cochrane Database of Systematic Reviews, Web of Science, China National Knowledge Infrastructure, Wanfang, Vip Journal Integration Platform) up to November 2016. Quality of all eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Pooled odds ratios (OR) and their 95% confidence intervals (95%CI) were calculated with fixed-effects or random-effects model to evaluate the effects of COX-2 expression on lymph node metastasis. A total of 27 studies with 1797 NPC patients met the inclusion criteria. The expression of COX-2 was significantly higher in patients with nasopharyngeal carcinoma than those without the carcinoma, with a combined OR of 21.17 (95%CI = 15.02-29.85, I2 = 35.1%, Pheterogeneity = 0.070). A statistically significant association between COX-2 expression and lymph node metastasis in NPC patients, with an OR of 4.44 (95%CI = 3.46-5.70, I2 = 38.3%, Pheterogeneity = 0.024), and with other indicators of disease progression. Subgroup analyses based on COX-2 assay and staging criteria of TNM showed no significant heterogeneity. The results suggest that expression of COX-2 is associated with lymph node metastasis and disease progression in NPC, indicating a potential role in evaluation of prognosis and in treatment decisions. COX-2 inhibitors have potential in the treatment of NPC that should be further investigated.


[Effect of magnesium lithospermate B on endothelial cells in human aorta after free radical injury].
To study the cardiovascular effects of magnesium lithospermate B (MLB), a water soluble extract from red sage root, on human aortic endothelial cells (HAECs) proliferation and in treating free radical injured endothelial cells, so as to further understand the cardiovascular pharmacological mechanism of MLB. HAECs of 3-6 passages were used in the experiment. MLB of different concentrations was used to treat the cells, and cell proliferation was observed using morphological and MTT method. The free radical injured model cell was made by glucose-glucose oxidase method for observing the effect of MLB on its microstructure by transmission electron microscopy. MLB in concentration of 1.0 mg/ml and 0.5 mg/ml had significant cytotoxicity (P<0.01), when its concentration was lower than 0.2 mg/ml, the drug showed no adverse reaction on cell proliferation. MLB showed significantly cell protective effect against free radical injury, the effect in protecting ultrastructure of cells, such as mitochondria, could be demonstrated in transmission electron microscopy. MLB showed a low cytotoxicity on HAECs, it could obviously protect cells from free radical injury.


Isotopic and elemental determination in some romanian apple fruit juices.
H, C, O stable isotope ratios and the content of some heavy elements of 31 Romanian single-strength organic apple juices collected from four Transylvanian areas are discussed in this study. The aim of this study was to measure the ²H/¹H, ¹⁸O/¹⁶O, ¹³C/¹²C ratios of these juices and their elemental profile and to establish a database of authentic values to be used for adulteration and authenticity testing. Our results have shown mean values of δ¹⁸O = -4.2‰ and δDδ-46.5‰, respectively, for apples from Transylvania and at the same time the mean value of δ¹³C = -28.2‰. The content of Cd, Pb, U, Zn, As was below the acceptable limits stipulated in US-EPA standard for drinking water. Cu and Cr limits exceeded for one single juice; Ni content for some apple juices from Maramures, Alba, and Cluj was higher than the acceptable value.


Enzymatic synthesis of a sucrose-containing linear polyester in nearly anhydrous organic media.
A variety of enzymes have been found to acylate sucrose in anhydrous pyridine. The enzymic reaction is highly selective; with trifluoroethylbutyrate as ester donor, enzyme-catalyzed transesterification of sucrose yielded sucrose 1'-butyrate and sucrose 6, 1'-dibutyrate. No sucrose-tributyrates were formed. Using a similar technique, a long-chain linear sucrose polyester has been prepared using Proleather, an alkaline protease from a Bacillus sp. This protease catalyzes the esterification of sucrose with bis(2, 2, 2-trifluoroethyladipate) in a 1:1 ratio to yield a sucrose-containing polyester with M(w) = 2100 and M(n) = 1600 for a polydispersity of 1. 31. Polymers with molecular weights in excess of 13, 000 have been prepared by this enzymic approach, indicating that molecules containing over 30 sucrose units have been produced. The polyester is extremely water soluble and soluble in polar organic solvents. As with the sucrose dibutyrate, the polyester has ester linkages at the C6 and C1' positions on the sucrose. The polyester can be depolymerized using Proleather in aqueous buffer, pH7. After 9 days in aqueous buffer, Proleather catalyzed the breakdown of the polyester to an M(w) of ca. 900. This sucrose-containing polyester may have applications as a water-absorbent, biodegradable plastic for use as diapers and hygienic products, water-treatment chemicals, and components of drug delivery systems.


[Management of Cervical Cancer Stage I B during Pregnancy].
Management and treatment of stage I B1 cervical cancer during pregnancy depends on the estimated gestational age and personal desires. We report 4 cases of stage I B1 cervical cancer during pregnancy that were treated differently. Case 1: A 29- year-old woman, primipara, visited our hospital at 7 weeks' gestation. She was diagnosed with a stage I B1 cervical cancer by using conization at 12 weeks' gestation. She strongly desired childbirth and therefore was treated at 29 weeks' gestation with a simultaneous cesarean section and radical surgery. Case 2: A 26-year-old woman, para 1, was diagnosed with stage I B1 cervical cancer at 23 weeks' gestation. She was treated at 28 weeks' gestation with a simultaneous cesarean section and radical surgery. Case 3: A 36-year-old woman, para 7, at 18 weeks' gestation, visited our hospital because of a stage I A cervical cancer. She chose to undergo abortion and radical surgery, which were performed simultaneously at 21 weeks' gestation. After the surgery, she was diagnosed with a stage I B1 cervical cancer pathologically. Case 4: A 33-year-old woman, para 2, was diagnosed with a stage I B2 cervical cancer at 30 weeks' gestation and was treated with a simultaneous cesarean section and radical surgery at 31 weeks' gestation.


COVID-19 Vaccination Attitudes and Intention: Message Framing and the Moderating Role of Perceived Vaccine Benefits.
The United States is one of the hardest-hit countries by the COVID-19 pandemic and yet there is widespread hesitancy to take the vaccine. In order to address vaccine hesitancy and foster public understanding of the COVID-19 vaccine, it is necessary to strategize public health messages based on evidence. To this end, we use experimental data to examine the effects of four message frames on participants' attitudes toward the COVID-19 vaccine and their vaccine intention. The primary purposes of this paper are to examine the 1) impact of loss vs. gain frames and individual vs. collective frames and 2) role of perceived benefits on participants' attitudes toward the COVID-19 vaccine and their vaccine intention. Our findings show that participants with higher perceived benefits and exposed to the loss frame showed higher positive attitudes toward the COVID-19 vaccine and greater intention to vaccinate. Similar patterns were revealed in case of the individual frame message. Implications are discussed.


Hyperglycemia aggravates decrease in alpha-synuclein expression in a middle cerebral artery occlusion model.
Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. α-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of α-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in α-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in α-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in α-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that α-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing α-synuclein expression.


Dead or Alive? Stillbirth Registration, Premature Babies, and the Definition of Life in England and Wales, 1836-1960.
When stillbirth registration became mandatory in England and Wales in 1926, it was not to amass statistics in the service of public health. Instead, it was part of broader anxieties that victims of infanticide were being disposed of under the guise of having been stillborn. But because it necessitated distinguishing between the living and the dead, the legislation that introduced stillbirth registration generated debate about the definition of life itself. This focused both on what counted as a sign of life and on questions about the viability of preterm infants. These contentious disputes had serious repercussions for the treatment of premature births well into the twentieth century. Significantly, they also underscore that what classifies a person as dead or alive is never self-evident. Instead, the state's authorized definition of life is under permanent negotiation as it is always mobilized in the service of particular regimes of power.


Induction of resistance in Mycobacterium smegmatis.
In this work, we assayed the ability of newly prepared indolizine derivates (epimers) 6C and 6A to inhibit the growth of Mycobacterium smegmatis and used them for resistance induction. 6A inhibited the growth of M. smegmatis at a concentration of 100 μg/mL. No inhibitory effect was observed in the presence of 6C. By incubating the bacteria with 6C and 6A, colonies resistant to 6A were observed. Finally, 37 stable resistant strains were isolated. These resistant strains were able to grow on a 5-fold higher concentration of 6A (500 μg/mL) than the minimal inhibitory concentration of the wild type (100 μg/mL), with no growth inhibition. Resistant strains were then tested for cross-resistance to other antibiotics: ampicillin, tetracycline, ciprofloxacin, chloramphenicol, gentamicin, and streptomycin. Determinations of resistance patterns to 6 antibiotics revealed 36 strains that were resistant to at least one drug.


Food environment and obesity.
The food environment plays an important and often dominant role in food choice, eating patterns, and ultimately, energy intake. The Obesity Society and the American Society for Nutrition jointly sponsored a series of reviews on topics of interest to both memberships. The goal was to consider the state of understanding on selected issues related to the food environment and obesity and to identify key knowledge gaps. The first article (not necessarily of importance) targeted energy density (ED) and focuses on the role of ED in the regulation of energy intake and body weight. It offers recommendations for prioritizing research. The second article addresses economic factors and examines food and beverage purchases as a function of price changes. It concludes that targeted food taxes and subsidies alone are unlikely to substantially affect obesity. The third article concerns sweetened beverages and points out the difficulty in establishing the strength of the association between intake of sugar-sweetened beverages and weight gain and obesity. In the fourth article, the contributions of palatability and variety to eating behavior and weight are reviewed. Article five explores the influence of portion size on energy intake and weight management. It finds that consumers generally tend to eat proportionally more as portion size increases. The sixth article focuses on the efficacy and effectiveness of eating frequency manipulations for body weight management and finds that such manipulations have consistently yielded null results. Finally, article seven identifies several limitations of the existing literature regarding neighborhood access to healthy foods. This series of reviews addresses important questions regarding the contribution of the food environment to obesity. Independent of physiological/genetic determinants, factors such as ED, cost, food form, palatability, variety, portion size, eating frequency, and access to healthy food are each evaluated for their role in the etiology of obesity and metabolic health. This series of reviews also identifies important gaps in knowledge.