PROTECTIVE EFFECT OF POMEGRANATE SEED OIL AGAINST MERCURIC CHLORIDE-INDUCED HEPATOTOXICITY IN RAT.
Mercuric chloride (HgCL2) is an environmental and industrial toxicant that affects many tissues. Considering oxidative stress is an important component of mercury induced hepatotoxicity, antioxidants are expected to play a protective role against it. The present study was designed to investigate the probable effects of pomegranate seed oil (PSO) on hepatotoxicity induced by HgCL₂, administration in rats. Rats were divided into five groups. Group 1 and 2 received corn oil (1 mL/kg, i.p.) and PSO (0.8 mL/kg, i.p.), respectively. Group 3 was treated with HgCl, (5 mg/kg, i.p.) for 3 days. In groups 4 and 5 PSO (0.4 and 0.8 mL/kg i.p., respectively) was given 1 h before HgCl2 administration. Twenty four hours after last injection of HgCl2, blood samples and specimens of liver were taken. HgCl2 administration led to significant increase in liver malondialdehyde level, significant reduction in total sulfhydryl content and significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase activity (AST), compared to control group. The histopathological changes such as necrosis, inflammatory cell infiltration and hepatocellular vacuolization were observed. PSO administration (0.8 mL/kg i.p.) improved the liver function in HgCL2 intoxicated animals as indicated by the significant decline in increased levels of AST, ALT in serum, MDA level and significant elevation in decreased total sulfhydryl content. Histological studies revealed milder hepatic lesions in PSO treated samples. The results indicated that oxidative stress may be an important mechanism of HgCl₂ induced hepatic injury and dysfunction and PSO may be a useful agent for the prevention of HgCl₂ induced oxidative damage in rat liver.


Demographics of patients older than 50 years with keratoconus.
This study was designed to determine the demographics of patients aged 50 years or more with a diagnosis of keratoconus, who were seen on the Cornea Service at Wills Eye Hospital. A retrospective chart review of all patients with the diagnosis of keratoconus was undertaken to identify demographics characteristics between January 1, 2005 and December 31, 2005. A total of 697 patients were identified. Two hundred seventy-nine (40.0%) patients were age 50 years or more. The age ranged from 50 to 93 years (average 60.2 +/- 8.2 years). Keratoconus was diagnosed as a bilateral disease in 266 (95.3%) and as a unilateral disease in 13 patients (4.7%). In 186 patients (66.6% of the total), the average age at the time of diagnosis was 31.7 +/- 10.9 years (range from 13 to 70 years). Of the 279 patients, 167 had surgery (59.8%). In the group of 112 patients that did not have surgery, 25 (9.0%) were treated with glasses in both eyes, 85 (30.5%) with contact lenses in both eyes, and 2 (0.7%) with glasses in one eye and contact lenses in the other eye. The average time of follow-up was 13.6 +/- 10.5 years (range from 0.1 to 38.7 years). In a corneal referral practice, the number of patients older than 50 years with keratoconus is higher than previously reported in the literature. We believe that this is because our practice has a strong interest in both contact lenses and corneal surgery with the ability to follow up patients on a long-term basis.


The 'Oscar curse' or the price of women's development.
This article aims to reflect on the unconscious dynamics that sustain the shocking increase in feminicide in the world. It is observed that psychological and physical violence by the intimate partner has numerous facets, especially when the woman gains more or has more professional success than her partner. This violence can take a subtle form as rejection and betrayal in order to hurt the woman and destroy her self-esteem and success. Based on numerous studies and bibliography it is demonstrated that the main cause of violence by the intimate partner is the fear of the power of the feminine that has been present throughout history. Despite the evolution of women, historical violence reverberates in the 21st century as an intergenerational trauma causing great suffering in families and disturbances in interpersonal relationships.


Properties of autonomous 3'-->5' exonucleases.
Autonomous 3'-->5' exonucleases (AE) are not bound covalently to DNA polymerases, but they are often included into the replicative complexes. Intracellular AE overproduction in bacteria results in sharp suppression of mutagenesis, whereas inactivation of these enzymes in bacteria and fungi leads to an increase in mutagenesis frequency by 2-3 orders of magnitude. Correction of DNA polymerase errors in vitro occurs after addition of AE to the incubation medium. This correction is clearly manifested under conditions of mutational stress (during induced but not spontaneous mutagenesis), for instance, with an imbalance of dNTPs--error-prone conditions. At equimolar dNTP (error-free conditions), the correction is relatively weak. The gene knockout of both alleles of the major AE gene in mice does not influence spontaneous mutagenesis though a substantial increase could be expected. The frequency of induced mutagenesis has not been yet measured, though the inactivation of AE could increase the frequency of mutagenesis. Complete inactivation of the major AE leads to inflammatory myocarditis and a 5-fold reduction of life span of mice. Dominant heterozygous mutations were found in various loci of the AE gene, which caused the development of Aicardi-Goutieres (autosomal recessive encephalopathy) syndrome, familial chilblain lupus, systemic lupus erythematosus, retinal vasculopathy, and cerebral leukodystrophy. In the nucleus, AE have a corrective function, but after transition into cytoplasm these enzymes destroy aberrant DNA that appears during replication and thereby save the cells from autoimmune diseases. Depending on their intracellular localization, AE carry out various biological functions but employ the same mechanism of the catalyzed reactions.


The effect of cytokines on the activation-induced apoptosis of B cells in autoimmune NZB x NZW F1 mice.
Programmed cell death (apoptosis) is an essential process in the development of various tissues and its involvement has been proposed for the elimination of self-reactive immature T and B lymphocytes when self antigens are first encountered. In order to further investigate the role of apoptosis in the pathogenesis of autoimmune disease, the apoptosis of lipopolysaccharide (LPS)-activated B cells, peritoneal cells from NZB x NZW F1 (NZB/W F1) mice and nonautoimmune BALB/c mice were assayed using an in vitro culture system. Splenic B cells were isolated and then stimulated with LPS before further activated with crosslinking antimu antibody. In addition, the apoptosis of peritoneal cells induced by crosslinking antimu antibody was also analyzed. The data revealed that the specific apoptosis of both activated B cells and peritoneal cells induced by crosslinking antimu antibody was very similar comparing NZB/W F1 and nonautoimmune BALB/c mice. This activation-induced B-cells apoptosis could be rescued, however, with the addition of cytokines such as interleukin (IL)-5 or IL-10, to the culture. The results suggest that there is no endogenous defect in the apoptosis of activated B cells for autoimmune NZB/W F1 comparing nonautoimmune BALB/c mice. Notably, however, abnormally high levels of the type 2 T helper (Th2)-related cytokines such as IL-5 or IL-10 may play an important role in the abnormal expansion of activated B cells in autoimmune NZB/W F1 mice.


Restraint minimisation in mental health care: legitimate or illegitimate force? An ethnographic study.
Coercive practices, such as physical restraint, are used globally to respond to violent, aggressive and other behaviours displayed by mental health service users.1 A number of approaches have been designed to aid staff working within services to minimise the use of restraint and other restrictive practices. One such approach, the 'REsTRAIN Yourself' (RYS) initiative, has been evaluated in the UK. Rapid ethnography was used to explore the aspects of organisational culture and staff behaviour exhibited by teams of staff working within 14 acute admission mental health wards in the North West region of the English NHS. Findings comprise four core themes of space and place; legitimation; meaningful activity; and, therapeutic engagement that represent characteristics of daily life on the wards before and after implementation of the RYS intervention. Tensions between staff commitments to therapeutic relations and constraining factors were revealed in demarcations of ward space and limitations on availability of meaningful activities. The physical, relational and discursive means by which ward spaces are segregated prompts attention to the observed materialities of routine care. Legitimation was identified as a crucial discursive practice in the context of staff reliance upon coercion. Trauma-informed care represents a potentially alternative legitimacy.


Metabolic alterations induced by ischemia in primary cultures of astrocytes: merging 13C NMR spectroscopy and metabolic flux analysis.
Disruption of brain energy metabolism is the hallmark of cerebral ischemia, a major cause of death worldwide. Astrocytes play a key role in the regulation of brain metabolism and their vulnerability to ischemia has been described. Aiming to quantify the effects of an ischemic insult in astrocytic metabolism, primary cultures of astrocytes were subjected to 5 h of oxygen and glucose deprivation in a bioreactor. Flux distributions, before and after ischemia, were estimated by metabolic flux analysis using isotopic information and the consumption/secretion rates of relevant extracellular metabolites as constraints. During ischemia and early recovery, 30% of cell death was observed; several metabolic alterations were also identified reflecting a metabolic response by the surviving cells. In the early recovery ( approximately 10 h), astrocytes up-regulated glucose utilization by 30% and increased the pentose phosphate pathway and tricarboxylic acid cycle fluxes by three and twofold, respectively. Additionally, a two to fivefold enhancement in branched-chain amino acids catabolism suggested the importance of anaplerotic molecules to the fast recovery of the energetic state, which was corroborated by measured cellular ATP levels. Glycolytic metabolism was predominant in the late recovery. In summary, this work demonstrates that changes in fluxes of key metabolic pathways are implicated in the recovery from ischemia in astrocytes.


A review of positive blood cultures: identification and source of microorganisms and patterns of sensitivity to antibiotics.
All strains of bacteria and fungi isolated from blood cultures of patients hospitalized in a large primary and tertiary care center were studied prospectively for determination of their clinical significance and probable source. In some instances the immediate mortality rate was also determined. The sensitivity patterns of all aerobic organisms to antibiotics were studied in relation to the role of antibiotic therapy. A positive culture was obtained from 6.8% of all blood specimens cultured and these positive cultures represented 639 episodes of bacteremia or fungemia. The organism isolated most of ten was Escherichia coli, and the most common known source was the urinary tract. Anaerobic organisms were isolated from 9.2% of the episodes of bacteremia, with the bowel being the most common probable source of infection. Antibiotic sensitivity testing revealed that all staphylococci were sensitive to methicillin, but only 22% were sensitive to penicillin. No penicillin-resistant pneumococci were encountered. The Enterobacteriaceae exhibited such a high sensitivity to gentamicin that comparison of its activity with that of other, newer aminoglycosides was impossible.


Control of ovulation in mice by progesterone receptor-regulated gene networks.
The mid-cycle surge of luteinizing hormone (LH) induces ovulation, a process during which a fertilizable oocyte is released from a mature ovarian follicle. Although ovulation is a physiologically well-characterized event, the underlying molecular pathways remain poorly understood. Progesterone receptor (PGR), which mediates the biological effects of the steroid hormone progesterone, has emerged as a key regulator of ovulation in mice. The development of a progesterone-receptor-null (Pgr-null) mouse model confirmed a critical role of this hormone in ovulation because in these mutant mice, mature pre-ovulatory follicles fail to release the oocytes. This animal model has thus presented a unique opportunity to study the molecular pathways underlying ovulation. Gene-expression profiling experiments by several groups, using the ovaries of Pgr-null mice, revealed novel gene networks, which act downstream of PGR to control ovulation. These genes encode diverse molecules such as proteases, transcription factors, cell-adhesion molecules, modulators of vascular activities and regulators of inflammation. Functional analyses using gene-knockout mouse models have confirmed that some of these factors play critical roles during ovulation. The knowledge gained from these studies has helped us to understand better the molecular mechanisms that facilitate the release of oocytes from pre-ovulatory follicles. Further analysis of the role of molecular regulators of ovulation will help identify useful molecular targets that would allow the development of improved contraceptives and new therapeutics for anovulatory infertility.


Retinol-binding protein 4 in patients with gestational diabetes mellitus.
It is still unknown if serum retinol-binding protein 4 (RBP4) relates to metabolic control and the occurrence of gestational diabetes mellitus (GDM). We studied RBP4 levels in patients with insulin-treated GDM and healthy pregnant women twice during pregnancy. Sixty-three women with GDM and 38 healthy pregnant women were included. Serum RBP4 levels were measured at 24-28 weeks of gestation and 8 weeks later. Patients with GDM were treated with insulin. Serum RBP4 levels increased significantly between the two measurements in patients with GDM (p = 0.03). In patients with GDM, RBP4 concentrations at 33 weeks of gestation correlated positively with mean blood glucose, hemoglobin A1c values, and cord blood insulin values right after delivery. Regression analyses showed that the diagnosis of GDM (p = 0.04) and hemoglobin A1c levels (p < 0.001) were related to RBP4 levels at 33 weeks of gestation. Serum RBP4 levels increase during pregnancy in patients with insulin-treated GDM.


Two new ternary complexes of copper(II) with tetracycline or doxycycline and 1,10-phenanthroline and their potential as antitumoral: cytotoxicity and DNA cleavage.
This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxycycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells with the IC(50) values of 1.93 and 2.59 μmol L(-1) for compounds 1 and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.


Functional significance of the mandibular symphysis.
The purpose of this investigation was to relate the morphology of connective tissues in the mandibular symphysis to the behavioral and experimental evidence for mobility and mechanical stress at the symphysis. The anatomy of the symphysis was examined histologically in 6 mammalian orders encompassing 22 species. Behavioral and experimental evidence of stress during the power stroke of the chewing cycle correspond with stresses at the symphysis implied by the location and orientation of symphyseal connective tissues. These stresses are: (1) dorsoventral shear of the symphysis due to the transfer of force from balancing to chewing sides, (2) bending of the symphysis causing tension along the inferior and compression along superior borders due to torsion on the dentaries from the jaw closing muscles, and (3) antero-posterior shear of the symphysis due to an anteriorly directed stress on the chewing side. Interspecific comparisons suggest that leaf eaters can resist greater dorsoventral shear than fruit or insect eaters, but no correlations exist between diet and bending or antero-posterior shear. This suggests that chewing leaves requires larger biting forces.


Token transfers among great apes (Gorilla gorilla, Pongo pygmaeus, Pan paniscus, and Pan troglodytes): species differences, gestural requests, and reciprocal exchange.
Great apes appear to be the nonhuman primates most capable of recognizing trading opportunities and engaging in transfers of commodities with conspecifics. Spontaneous exchange of goods between them has not yet been reported. We tested gorillas (Gorilla gorilla), orangutans (Pongo pygmaeus), bonobos (Pan paniscus), and chimpanzees (Pan troglodytes) in a token-exchange task involving two conspecifics and a human experimenter. Tested in pairs, subjects had to exchange tokens with a partner to obtain food from the experimenter. We observed 4, 5, 264, and 328 transfers of tokens in gorillas, chimpanzees, orangutans, and bonobos, respectively. Most gifts were indirect in gorillas, chimpanzees, and bonobos, whereas most were direct in orangutans. The analysis showed no evidence of calculated reciprocity in interactions. A main finding of the study was the high rate of repeated gifts and begging gestures recorded in orangutans. This raises the question of the meaning of pointing in great apes and their ability to understand the communicative intent of others.


Selective enumeration strategies for Brevundimonas diminuta from drinking water.
Brevundimonas diminuta is used as a control organism for validating the efficiency of water filtration systems. Since these protocols use nonselective growth media, heterotrophic plate count bacteria (HPCs) indigenous to the water distribution system may interfere with B. diminuta enumeration, thus leading to inaccurate assessment of the filter's microbial reduction capability. This could negatively impact public health as unsafe drinking water may be produced. This study was conducted to evaluate different potential routes for selective enumeration of B. diminuta in drinking water. B. diminuta's biochemical and molecular relationships to HPCs recovered from a laboratory drinking-water system were investigated. Of the 24 HPC morphotypes recovered, members of the Alpha- and Betaproteobacteria were most commonly identified. Based on comparisons of catabolic profiles (generated by the Biolog system) using principal component analysis, B. diminuta possessed similar metabolic patterns to several of the Alphaproteobacteria (Sphingomonas and Caulobacter), indicating that development of a selective medium based solely on carbon source was not feasible. Antibiotic susceptibility profiles revealed that the HPCs were least resistant to kanamycin, making it a candidate for future selective applications. Sequence comparisons of partial 16S rRNA sequences did not reveal any distinct similarities. However, basic local alignment search tool (BLAST) alignments of the gyrB and rpoD sequences for B. diminuta did show uniqueness, with the next closest match being to Caulobacter (88% and 79% similarity, respectively). Future investigation will focus on applying molecular assays, such as fluorescent in situ hybridization and quantitative real-time polymerase chain reaction (PCR), and incorporating an antibiotic marker or expressed fluorescent protein into the wild-type strain of B. diminuta for selective enumeration of B. diminuta.


Morphology of dopaminergic amacrine cells in the mouse retina: independence from homotypic interactions.
To determine the role of homotypic interactions between neighboring dopaminergic amacrine (DA) cells upon dendritic morphogenesis, the morphology of single cells was examined relative to the positioning of all neighboring homotypic cells. For each labeled cell, the dendritic field was reconstructed, its Voronoi domain was calculated, and the two were related. The dendritic fields of DA cells were observed to be large, sparse, and highly irregular. Dendrites readily overlapped those of neighboring cells, showing no evidence for dendritic tiling or inter-digitation consistent with homotypic repulsion or avoidance. Furthermore, a direct comparison of dendritic field area with the Voronoi domain area of the same cell showed no evidence for dendritic growth being constrained or biased by the local distribution of homotypic neighbors in wild-type retinas. A comparison of the processes of adjacent filled cells confirmed their immediate proximity to one another within the inner plexiform layer, indicating that they do not engage in mutual avoidance by coursing at different depths. Together, these results suggest that the morphogenesis of DA cells is independent of homotypic interactions. However, in the absence of the pro-apoptotic Bax gene, which yields a fourfold increase in DA cell number, a small but significant reduction in dendritic field size was obtained, although not so great as would be predicted by the increase in density. The present results are considered in light of recent studies on the role of cell adhesion molecules expressed by developing DA cells.


RBC Distribution Width: Biomarker for Red Cell Dysfunction and Critical Illness Outcome?
RBC distribution width is reported to be an independent predictor of outcome in adults with a variety of conditions. We sought to determine if RBC distribution width is associated with morbidity or mortality in critically ill children. Retrospective observational study. Tertiary PICU. All admissions to St. Louis Children's Hospital PICU between January 1, 2005, and December 31, 2012. We collected demographics, laboratory values, hospitalization characteristics, and outcomes. We calculated the relative change in RBC distribution width from admission RBC distribution width to the highest RBC distribution width during the first 7 days of hospitalization. Our primary outcome was ICU mortality or use of extracorporeal membrane oxygenation as a composite. Secondary outcomes were ICU- and ventilator-free days. We identified 3,913 eligible subjects with an estimated mortality (by Pediatric Index of Mortality 2) of 2.94% ± 9.25% and an actual ICU mortality of 2.91%. For the study cohort, admission RBC distribution width was 14.12% ± 1.89% and relative change in RBC distribution width was 2.63% ± 6.23%. On univariate analysis, both admission RBC distribution width and relative change in RBC distribution width correlated with mortality or the use of extracorporeal membrane oxygenation (odds ratio, 1.19 [95% CI, 1.12-1.27] and odds ratio, 1.06 [95% CI, 1.04-1.08], respectively; p < 0.001). After adjusting for confounding variables, including severity of illness, both admission RBC distribution width (odds ratio, 1.13; 95% CI, 1.03-1.24) and relative change in RBC distribution width (odds ratio, 1.04; 95% CI, 1.01-1.07) remained independently associated with ICU mortality or the use of extracorporeal membrane oxygenation. Admission RBC distribution width and relative change in RBC distribution width both weakly correlated with fewer ICU- (r = 0.038) and ventilator-free days (r = 0.05) (p < 0.001). Independent of illness severity in critically ill children, admission RBC distribution width is associated with ICU mortality and morbidity. These data suggest that RBC distribution width may be a biomarker for RBC injury that is of sufficient magnitude to influence critical illness outcome, possibly via oxygen delivery impairment.


Sound arithmetic: auditory cues in the rehabilitation of impaired fact retrieval.
The present single case study describes the rehabilitation of an acquired impairment of multiplication fact retrieval. In addition to a conventional drill approach, one set of problems was preceded by auditory cues while the other half was not. After extensive repetition, non-specific improvements could be observed for all trained problems (e.g., 3 * 7) as well as for their non-trained complementary problems (e.g., 7 * 3). Beyond this general improvement, specific therapy effects were found for problems trained with auditory cues. These specific effects were attributed to an involvement of implicit memory systems and/or attentional processes during training. Thus, the present results demonstrate that cues in the training of arithmetic facts do not have to be visual to be effective.


[The occurrence of goitrogenic substances in milk. 1. Release of goitrin in the milk of cows fed on rapeseed extract cakes].
A total of six cows, divided into 3 groups, were fed various amounts of rape cake containing 6 g of goitrin/kg over a period of 7 days. The cows were milked twice a day and the goitrin content of the heated milk samples were determined by a HPLC-method within 2 h. When rape cake was fed at 0.39, 1.9 and 3.9% resp. of the total feed this resulted in medium goitrin values of 37, 163 and 707 micrograms/l milk. These values correspond to a transfer of about 0.1% of the original progoitrin content in the feed. 12 h after the last rape feeding the amount of goitrin in the milk was below the detection limit of 7 ppb. The toxicological significance of these findings are dicussed.


Quantitative proteomic approach for cellulose degradation by Neurospora crassa.
Conversion of plant biomass to soluble sugars is the primary bottleneck associated with production of economically viable cellulosic fuels and chemicals. To better understand the biochemical route that filamentous fungi use to degrade plant biomass, we have taken a quantitative proteomics approach to characterizing the secretome of Neurospora crassa during growth on microcrystalline cellulose. Thirteen proteins were quantified in the N. crassa secretome using a combination of Absolute Quantification (AQUA) and Absolute SILAC to verify protein concentrations. Four of these enzymes including 2 cellobiohydrolases (CBH-1 and GH6-2), an endoglucanase (GH5-1), and a β-glucosidase (GH3-4) were then chosen to reconstitute a defined cellulase mixture in vitro. These enzymes were assayed alone and in mixtures and the activity of the reconstituted set was then compared to the crude mixture of N. crassa secretome proteins. Results show that while these 4 proteins represent 63-65% of the total secretome by weight, they account for just 43% of the total activity on microcrystalline cellulose after 24 h of hydrolysis. This result and quantitative proteomic data on other less abundant proteins secreted by Neurospora suggest that proteins other than canonical fungal cellulases may play an important role in cellulose degradation by fungi.


Total synthesis and structure confirmation of the annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin a, and 5(R)-uvarigrandin a (narumicin I?).
A synthesis of the bistetrahydrofuran Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin A through application of a previously disclosed four-component modular approach is described in which extended core segments are coupled to a C4- or C5-hydroxy butenolide terminus. The butenolide termini segments were prepared from (S)- or (R)-malic acid. Spectral properties of synthetic 30(S)-hydroxybullatacin and uvarigrandin A, as well as their Mosher ester derivatives, were in close agreement to the reported values for the natural substances. The synthetic 5(R)-uvarigrandin A is possibly identical to narumicin I, but subtle differences in the reported NMR spectra prevented an unambiguous assessment of this point.


Evaluation of Free Breathing Versus Breath Hold Diffusion Weighted Imaging in Terms Apparent Diffusion Coefficient (ADC) and Signal-to-Noise Ratio (SNR) Values for Solid Abdominal Organs.
Our aim was to compare the apparent diffusion coefficient (ADC) values of normal abdominal parenchymal organs and signal-to-noise ratio (SNR) measurements in the same patients with breath hold (BH) and free breathing (FB) diffusion weighted imaging (DWI). Forty-eight patients underwent both BH and FB DWI. Spherical region of interest (ROI) was placed on the right hepatic lobe, spleen, pancreas, and renal cortices. ADC values were calculated for each organ on each sequence using an automated software. Image noise, defined as the standard deviation (SD) of the signal intensities in the most artifact-free area of the image background was measured by placing the largest possible ROI on either the left or the right side of the body outside the object in the recorded field of view. SNR was calculated using the formula: SNR=signal intensity (SI)(organ)/standard deviation (SD)(noise). There were no statistically significant differences in ADC values of the abdominal organs between BH and FB DWI sequences (p>0.05). There were statistically significant differences between SNR values of organs on BH and FB DWIs. SNRs were found to be better on FB DWI than BH DWI (p<0.001). Free breathing DWI technique reduces image noise and increases SNR for abdominal examinations. Free breathing technique is therefore preferable to BH DWI in the evaluation of abdominal organs by DWI.


Awakening to the alcohol epidemic - need of the hour.
Globally, alcohol has become the most common risk factor for death and disability in the young age group of 15-49 years. Its use has been rapidly increasing in developing countries. It is a critical time wherein if effective preventive measures are not undertaken urgently, damage done will be difficult to reverse. However, health professionals are not responding to the alcohol epidemic in the manner that they responded to the tobacco epidemic. The article discusses two beliefs which are making us accept the use of alcohol as normal. Recent evidence indicates that it is not advisable to drink alcohol even in moderation. Furthermore, social drinking has failed to decrease alcohol-related harm in western countries. Because of its addictive nature, many people end up drinking excessively though they do not intend to. Hence, we need to shift our focus from only "reducing harmful use of alcohol" to "reducing use of alcohol" in general.


Downregulation of microRNA‑494 inhibits cell proliferation in lung squamous cell carcinoma via the induction of PUMA‑α‑mediated apoptosis.
Increased evidence has shown that abnormal microRNA (miRNA) plays pivotal roles in numerous types of cancer. However, their expression, function and mechanism in lung squamous cell carcinoma (LSCC) remains to be fully elucidated. The aim of the present study was to investigate the suppressive role of miR-494 in LSCC progression and elucidate its regulatory mechanism. By analyzing expression profiles of miRNAs in LSCC tissues using miRNA microarray, it was revealed that miR-494 was significantly upregulated in 22 pairs of LSCC tissues. Subsequently, reverse transcription-quantitative PCR was performed to determine the expression of miR-494 and p53-upregulated-modulator-of-apoptosis-α (PUMA-α). Western blot analysis was conducted to examine protein levels. Dual-luciferase reporter assay was used to confirm the binding between miR-494 and PUMA-α. Annexin V-fluoresceine isothiocyanate/propidium iodide staining and CCK-8 assays were employed to determine cell apoptosis and cell viability, respectively. It was also revealed that miR-494 was highly expressed in LSCC cell lines compared with that in 16HBE cells. Further experiments confirmed that knockdown of miR-494 reduced cell viability and induced LSCC apoptosis. Bioinformatics analysis predicted that miR-494 could potentially target PUMA-α; also known as Bcl-2-binding component 3, a pro-apoptotic factor, and an inverse correlation between the expression of miR-494 and PUMA-α mRNA levels in LSCC tissues was found. Furthermore, PUMA-α inhibition could reverse the promoting effect of miR-494 knockdown on apoptosis in LSCC cells. Taken together, these findings demonstrated that miR-494 functions as an oncogene by targeting PUMA-α in LSCC, and miR-494 may serve as a novel therapeutic target for treating LSCC.


Excited state proton transfer is not involved in the ultrafast deactivation of Guanine-Cytosine pair in solution.
Different derivatives of Guanine (G) and Cytosine (C), which sterically enforce the Watson-Crick (WC) conformer, have been studied in CHCl(3) by means of broad-band transient absorption spectroscopy. Our experiments rule out the involvement of an Excited State Proton Transfer (ESPT), which dominates the excited state decay of GC in the gas phase. Instead, the ultrafast dynamics via internal conversion occurs in a polar environment mainly by relaxation in the monomer moieties. Time-dependent density functional theory (TD-DFT) calculations in solution indeed indicate that population transfer from the bright excited states toward the charge transfer state is not effective in CHCl(3) and a noticeable energy barrier is associated with the ESPT reaction. ESPT is therefore not expected to be a main deactivation route for GC pairs within DNA.


Controlled growth of large-area anisotropic ReS2 atomic layer and its photodetector application.
As an anisotropic 2D layered material, rhenium disulfide (ReS2) has attracted much attention because of its unusual properties and promising applications in electronic and optoelectronic devices. However, the low lattice symmetry and interlayer decoupling of ReS2 make asymmetric growth and out-of-plane growth occur quite easily; therefore, thick flake, dendritic and flower-like structures of ReS2 have mostly been obtained previously. Here, we report on an approach based on space-confined epitaxial growth for the controlled synthesis of ReS2 films. Using this approach, large-area and high-quality ReS2 films with uniform monolayer thickness can grow on a mica substrate. Furthermore, the weak van der Waals interaction between the surface of mica and ReS2 clusters, which favors surface-confined growth while avoiding out-of-plane growth, is critical for growing ReS2 with uniform monolayer thickness. The morphological evolution of ReS2 with the growth temperature reveals that asymmetric growth can be suppressed at relatively low temperatures. A ReS2 field-effect transistor displayed a current on/off ratio of 106 and an electron mobility of up to 40 cm2 V-1 s-1, with outstanding photoresponsivity of 12 A W-1. This work not only promotes the large-scale employment of ReS2 in high-performance optoelectronic devices, but also provides a means of controlling the unusual growth behavior of low-lattice-symmetry 2D layered materials.


Role of miR-128 in hypertension-induced myocardial injury.
The present study aimed to investigate the role and mechanism of micro RNA (miR)-128 in hypertension-induced myocardial injury. The peripheral blood of patients with hypertension was collected and the expression of miR-128 was detected using fluorescence reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary myocardial cells isolated from rat in vitro were cultured under conditions of hypoxia and glucose deprivation, and miR-128 expression was measured by RT-qPCR. The expression of c-Met protein was measured using western blot analysis and the apoptosis of transfected cells was measured by flow cytometry in rat myocardial cells following transfection with miR-128 mimics or c-Met siRNA. A luciferase assay was applied to assess the binding of miR-128 to c-Met mRNA. miR-128 expression was significantly higher in hypertension patients compared with controls (P<0.05). miR-128 expression was higher in patients with stage III/IV hypertension compared with patients with stage II hypertension. Similarly, miR-128 expression in primary cardiomyocytes cultured under deprivation of oxygen and glucose increased with the culture time and reached a peak at 12 h. c-Met expression decreased significantly (P<0.05) and the ratio of apoptotic cells increased significantly (P<0.05), following transfection of miR-128 mimics. The number of apoptotic cells also increased when c-Met expression was knocked down by siRNA. The dual luciferase assay indicated that fluorescence intensity decreased significantly in miR-128 mimics and wild type c-Met group (P<0.05), indicating that miR-128 can directly target c-Met. Therefore, the results of the current study suggest that miR-128 may promote myocardial cell injury by regulating c-Met expression.


[Minimizing the antigenicity of tracheal allografts by using a technique of cryopreservation].
To investigate the proper time of cryo-preserving tracheal allograft so as to minimize its antigenicity. On a dog model, this study was carried out by allografting a tracheal into a muscular flap formed with sternocephalic muscle and sternohyoid--sternothyroid muscle. The tracheal was treated with cryopreservation in defferent intervals. The viability of the graft was evaluated by the examination of fiberoptic bronchoscopy, histopathology and microangiography. The blood flow of the tracheal mucous was measured with a blood flowmeter and the survival area was decided in the calculation of the percentage. There are no significant differences in the mucous membrane appearance and the mucosal blood flow one week after the surgery among the non-cryopreservation group and the groups treated with cryopreservation in 1 day, 2 weeks, 4 weeks, 6 weeks and 8 weeks. The graft was found to start necrosis 2 weeks after the transplantation with the infiltration of mononuclear cells examined under light microscope in almost all of the groups, especially in the non-cryopreservation group and the groups treated with cryopreservation in 1 day, 2 weeks. However, there was no significant difference among the autograft group and the allograft groups cryopreservated in 6 weeks and 8 weeks, and the infiltration of the mononuclear cells was not found in these groups either. The antigenicity of the tracheal allografts could be significantly decreased by the treatment of cryopreservation over 6 weeks.


[A Case of Gastric Granular Cell Tumor Resected by a Surgical Robot].
A 46-year-old man was referred to further treatment for a 20 mm submucosal tumor at the gastric angle found during a medical check-up. Endoscopic ultrasonography and chest abdominal contrast-enhanced CT revealed the tumor was located at the 4th(proper muscular)layer of the posterior wall of the gastric antrum and slightly enhanced. No metastasis was found. Although a biopsy failed to reveal an accurate diagnosis, GIST was clinically suspected. A robotic distal gastrectomy was planned to manage the residual gastric stricture. The intraoperative findings indicated possible passage of the remnant stomach; therefore, local resection was performed. The patient's postoperative course was uneventful, and he was discharged on postoperative day 9. A histopathological examination confirmed the diagnosis of a PAS-positive, S100-positive granular cell tumor with no nuclear atypia. These findings suggest that use of the robotic approach could help determine the stomach resection extent.


Aerosolized ZnO nanoparticles induce toxicity in alveolar type II epithelial cells at the air-liquid interface.
The majority of in vitro studies characterizing the impact of engineered nanoparticles (NPs) on cells that line the respiratory tract were conducted in cells exposed to NPs in suspension. This approach introduces processes that are unlikely to occur during inhaled NP exposures in vivo, such as the shedding of toxic doses of dissolved ions. ZnO NPs are used extensively and pose significant sources for human exposure. Exposures to airborne ZnO NPs can induce adverse effects, but the relevance of the dissolved Zn(2+) to the observed effects in vivo is still unclear. Our goal was to mimic in vivo exposures to airborne NPs and decipher the contribution of the intact NP from the contribution of the dissolved ions to airborne ZnO NP toxicity. We established the exposure of alveolar type II epithelial cells to aerosolized NPs at the air-liquid interface (ALI) and compared the impact of aerosolized ZnO NPs and NPs in suspension at the same cellular doses, measured as the number of particles per cell. By evaluating membrane integrity and cell viability 6 and 24 h post-exposure, we found that aerosolized NPs induced toxicity at the ALI at doses that were in the same order of magnitude as doses required to induce toxicity in submersed cultures. In addition, distinct patterns of oxidative stress were observed in the two exposure systems. These observations unravel the ability of airborne ZnO NPs to induce toxicity without the contribution of dissolved Zn(2+) and suggest distinct mechanisms at the ALI and in submersed cultures.


Comparison of two infrared devices in their effectiveness in reducing symptoms associated with RLS.
This study was conducted to assess whether two kinds of near-infrared light devices, using different wavelengths and frequencies, impact symptoms associated with restless legs syndrome (RLS) differently. A recent randomized controlled study showed that symptoms associated with RLS can be diminished with near-infrared light treatment for a limited time. We wanted to assess whether different wavelengths and frequencies had an impact on its effectiveness. Twenty-five volunteers with symptoms of RLS were randomly assigned to either Anodyne® or HealthLight™ treatment. Both groups underwent 12 treatments with near-infrared light, three times a week for 4 weeks. A validated RLS rating scale was used to track changes. The two groups were not different in reported symptoms at baseline (p=0.37) and after 4 weeks of treatment (p=0.88). There was a significant improvement of symptoms between week 0 and week 4 (p<0.001); the difference in change indicated virtually the same improvement between the two groups. Although the two near-infrared light devices used different wavelengths and frequencies and one device used additional red light, they both produced significant improvement in the symptoms associated with RLS after 4 weeks of treatment.


Strategies and action points to ensure equitable uptake of COVID-19 vaccinations: A national qualitative interview study to explore the views of undocumented migrants, asylum seekers, and refugees.
Early evidence confirms lower COVID-19 vaccine uptake in established ethnic minority populations, yet there has been little focus on understanding vaccine hesitancy and barriers to vaccination in migrants. Growing populations of precarious migrants (including undocumented migrants, asylum seekers and refugees) in the UK and Europe are considered to be under-immunised groups and may be excluded from health systems, yet little is known about their views on COVID-19 vaccines specifically, which are essential to identify key solutions and action points to strengthen vaccine roll-out. We did an in-depth semi-structured qualitative interview study of recently arrived migrants (foreign-born, >18 years old; <10 years in the UK) to the UK with precarious immigration status between September 2020 and March 2021, seeking their input into strategies to strengthen COVID-19 vaccine delivery and uptake. We used the 'Three Cs' model (confidence, complacency and convenience) to explore COVID-19 vaccine hesitancy, barriers and access. Data were analysed using a thematic framework approach. Data collection continued until data saturation was reached, and no novel concepts were arising. The study was approved by the University of London ethics committee (REC 2020.00630). We approached 20 migrant support groups nationwide, recruiting 32 migrants (mean age 37.1 years; 21 [66%] female; mean time in the UK 5.6 years [SD 3.7 years]), including refugees (n = 3), asylum seekers (n = 19), undocumented migrants (n = 8) and migrants with limited leave to remain (n = 2) from 15 different countries (5 WHO regions). 23 (72%) of 32 migrants reported being hesitant about accepting a COVID-19 vaccine and two (6%) would definitely not accept a vaccine. Participants communicated concerns over vaccine content, side-effects, lack of accessible information in an appropriate language, lack of trust in the health system and low perceived need. A range of barriers to accessing the COVID-19 vaccine were reported and concerns expressed that their communities would be excluded from or de-prioritised in the roll-out. Undocumented migrants described fears over being charged and facing immigration checks if they present for a vaccine. Participants (n = 10) interviewed after recent government announcements that COVID-19 vaccines can be accessed without facing immigration checks remained unaware of this. Participants stated that convenience of access would be a key factor in their decision around whether to accept a vaccine and proposed alternative access points to primary care services (for example, walk-in centres in trusted places such as foodbanks, community centres and charities), alongside promoting registration with primary care for all, and working closely with communities to produce accessible information on COVID-19 vaccination. Precarious migrants may be hesitant about accepting a COVID-19 vaccine and face multiple and unique barriers to access, requiring simple but innovative solutions to ensure equitable access and uptake. Vaccine hesitancy and low awareness around entitlement and relevant access points could be easily addressed with clear, accessible, and tailored information campaigns, co-produced and delivered by trusted sources within marginalised migrant communities. These findings have immediate relevance to the COVID-19 vaccination initiatives in the UK and in other European and high-income countries with diverse migrant populations. NIHR.


Health care reform in the states.
Challenged by relentless increases in health care spending, state governments have been forced to experiment with health care system reform. Medicaid has been expanded by Congress, forcing states to provide a broader array of health benefits to more recipients. As states consider reform, federal limitations mandated by Medicaid and by the Employee Retirement Income Security Act (ERISA) of 1974 on state activity pose significant obstacles. ERISA sharply limits a state's ability to raise revenue to fund these health programs. Several states have responded to these limitations by seeking waivers. Despite these obstacles, 8 states already have enacted comprehensive health reform measures, and virtually every state is considering legislative reform.


Near infrared reflection spectra of artificial cumulus clouds.
Reflection spectra are presented for artificial cumulus clouds with a progression of droplet sizes, including sizes common in natural clouds, over the wavelength range from 1.0 micro to 2.4 micro. A correction is made for gaseous absorption. The spectra show reflectivity minima at 1.16 micro, 1.41 micro, and 1.92micro which deepen as the droplets become larger and are in good agreement with reflection spectra of terrestrial clouds.


Proliferation of Ty3/gypsy-like retrotransposons in hybrid sunflower taxa inferred from phylogenetic data.
Long terminal repeat (LTR) retrotransposons are a class of mobile genetic element capable of autonomous transposition via an RNA intermediate. Their large size and proliferative ability make them important contributors to genome size evolution, especially in plants, where they can reach exceptionally high copy numbers and contribute substantially to variation in genome size even among closely related taxa. Using a phylogenetic approach, we characterize dynamics of proliferation events of Ty3/gypsy-like LTR retrotransposons that led to massive genomic expansion in three Helianthus (sunflower) species of ancient hybrid origin. The three hybrid species are independently derived from the same two parental species, offering a unique opportunity to explore patterns of retrotransposon proliferation in light of reticulate evolutionary events in this species group. We demonstrate that Ty3/gypsy-like retrotransposons exist as multiple well supported sublineages in both the parental and hybrid derivative species and that the same element sublineage served as the source lineage of proliferation in each hybrid species' genome. This inference is based on patterns of species-specific element numerical abundance within different phylogenetic sublineages as well as through signals of proliferation events present in the distributions of element divergence values. Employing methods to date paralogous sequences within a genome, proliferation events in the hybrid species' genomes are estimated to have occurred approximately 0.5 to 1 million years ago. Proliferation of the same retrotransposon major sublineage in each hybrid species indicates that similar dynamics of element derepression and amplification likely occurred in each hybrid taxon during their formation. Temporal estimates of these proliferation events suggest an earlier origin for these hybrid species than previously supposed.


Graphene oxide-based supramolecular hydrogels for making nanohybrid systems with Au nanoparticles.
In the presence of a small amount of a proteinous amino acid (arginine/tryptophan/histidine) or a nucleoside (adenosine/guanosine/cytidine), graphene oxide (GO) forms supramolecular stable hydrogels. These hydrogels have been characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray diffraction (XRD) analysis, Raman spectroscopy, and rheology. The morphology of the hydrogel reveals the presence of nanofibers and nanosheets. This suggests the supramolecular aggregation of GO in the presence of an amino acid/nucleoside. Rheological studies of arginine containing a GO-based hydrogel show a very high G' value (6.058 × 10(4) Pa), indicating the rigid, solid-like behavior of this gel. One of these hydrogels (GO-tryptophan) has been successfully utilized for the in situ synthesis and stabilization of Au nanoparticles (Au NPs) within the hydrogel matrix without the presence of any other external reducing and stabilizing agents to make Au NPs containing the GO-based nanohybrid material. The Au NPs containing the hybrid hydrogel has been characterized by using UV/vis spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). In this study, gold salt (Au(3+)) has been bioreduced by the tryptophan within the hydrogel. This is a facile "green chemical" method of preparing the GO-based nanohybrid material within the hydrogel matrix. The significance of this method is the in situ reduction of gold salt within the gel phase, and this helps to decorate the nascently formed Au NPs almost homogeneously and uniformly on the surface of the GO nanosheets within the gel matrix.


Weight change over two years in people prescribed olanzapine, quetiapine and risperidone in UK primary care: Cohort study in THIN, a UK primary care database.
Follow-up studies of weight gain related to antipsychotic treatment beyond a year are limited in number. We compared weight change in the three most commonly prescribed antipsychotics in a representative UK General Practice database. We conducted a cohort study in United Kingdom primary care records of people newly prescribed olanzapine, quetiapine or risperidone. The primary outcome was weight in each six month period for two years after treatment initiation. Weight changes were compared using linear regression, adjusted for age, baseline weight and diagnosis. N = 6338 people received olanzapine, 12,984 quetiapine and 6556 risperidone. Baseline weight was lowest for men treated with olanzapine (80.8 kg versus 83.5 kg quetiapine, 82.0 kg risperidone) and women treated with olanzapine (67.7 kg versus 71.5 kg quetiapine 68.4 kg risperidone. Weight gain occurred during treatment with all three drugs. Compared with risperidone mean weight gain was higher with olanzapine (adjusted co-efficient +1.24 kg (95% confidence interval: 0.69-1.79 kg per six months) for men and +0.77 kg (95% confidence interval: 0.29-1.24 kg) for women). Weight gain with quetiapine was lower in unadjusted models compared with risperidone, but this difference was not significant after adjustment. Olanzapine is more commonly prescribed to people with lower weight. However, after accounting for baseline weight, age, sex and diagnosis, olanzapine is still associated with greater weight gain over two years than risperidone or quetiapine. Baseline weight does not ameliorate the risks of weight gain associated with antipsychotic medication. Weight gain should be assertively discussed and managed for people prescribed antipsychotics, especially olanzapine.


Reprogramming of Energy Metabolism: Increased Expression and Roles of Pyruvate Carboxylase in Papillary Thyroid Cancer.
Background: Energy metabolism is described to be deregulated in cancer, and the Warburg effect is considered to be a major hallmark. Recently, cellular heterogeneity in tumors and the tumor microenvironment has been recognized to play an important role in several metabolic pathways in cancer. However, its contribution to papillary thyroid cancer (PTC) development and metabolism is still poorly understood. Methods: A proteomic analysis of five PTC was performed, and the cellular distribution of several upregulated metabolic proteins was investigated in the cancerous and stromal cells of these tumors. Results: Tandem mass spectrometry analysis revealed the upregulation of many metabolism-related proteins, among them pyruvate carboxylase (PC). PC knockdown in thyroid cell lines alters their proliferative and motility capacities, and measurements of oxygen consumption rates show that this enzyme is involved in the replenishment of the tricarboxylic acid cycle. Immunostainings of several upregulated metabolic proteins show that thyroid cancer cells have an increased mitochondrial oxidative metabolism compared to stromal cells. Conclusions: PTC has a very active tricarboxylic acid cycle, continuously replenished by a PC-mediated anaplerosis. This is specifically observed in the tumor cells.


Effects of extracellular delta-aminolaevulinic acid on sodium currents in acutely isolated rat hippocampal CA1 neurons.
The effects of delta-aminolaevulinic acid (ALA) on voltage-gated sodium channel (VGSC) currents (I(Na)) in acutely isolated hippocampal CA1 neurons from 10- to 12-day-old Wistar rats were examined by using the whole-cell patch-clamp technique under voltage-clamp conditions. ALA from 0.01 microm to 20 microm was applied to the recorded neurons. Low concentrations of ALA (0.01-1.0 microM) increased I(Na) amplitude, whereas high concentrations of ALA (5.0-20.0 microM) decreased it. The average I(Na) amplitude reached a maximum of 117.4 +/- 3.9% (n = 9, P < 0.05) with 0.1 microM ALA, and decreased to 78.1 +/- 3.8% (n = 13, P < 0.05) with 10 microm ALA. ALA shifted the steady-state activation and inactivation curves of I(Na) in the hyperpolarizing direction with different V0.5, suggesting that ALA could depress the opening threshold of the voltage-gated sodium channel (VGSC) and thus increase the excitability of neurons through facilitating the opening of VGSC. The time course of recovery from inactivation was significantly prolonged at both low and high concentrations of ALA, whereas either low or high concentrations of ALA had no significant effect on the attenuation of I(Na) during stimulation at 5 Hz, indicating that the effect of ALA on VGSC is state-independent. Furthermore, we found that application of ascorbic acid, which blocks pro-oxidative effects in neurons, could prevent the increase of I(Na) amplitude at low concentrations of ALA. Baclofen, an agonist of GABAb receptors, induced some similar effects to ALA on VGSC, whereas bicuculline, an antagonist of GABAa receptors, could not prevent ALA-induced effects on VGSC. These results suggested that ALA regulated VGSC mainly through its pro-oxidative effects and GABAb receptor-mediated effects.


Ambulatory visits, active component, U.S. Armed Forces, 2021.
In 2021, the overall numbers and rates of active component service member ambulatory care visits were the highest of any of the last 10 years. Most categories of illness and injury showed modest increases in numbers and rates. The proportions of ambulatory care visits that were accomplished via telehealth encounters fell to under 15% in 2021, compared to 19% in 2020. Although the response to the COVID-19 pandemic in 2020 may have been associated with decreases in the incidence of disease and injury diagnoses in the service member population receiving ambulatory care, the data for 2021 show a return to pre-pandemic levels. Moreover, the proportions of health care encounters delivered through telehealth have similarly reverted to the lower levels seen in the pre-pandemic period. Lessons learned may guide future steps in reducing disease and injury incidence in the postpandemic era.


Perspectives on medicinal properties of mangiferin.
Mango tree, Mangifera indica, has been cultivated in India and several other tropical countries for centuries, and it is a good source of compound 'mangiferin'. Mangiferin's xanthonoid structure with C-glucosyl linkage and polyhydroxy component is believed to be crucial for its free radical-scavenging ability leading to a potent antioxidant effect. A number of biological activities of mangiferin have been suggested, including antidiabetic and antiinflammatory abilities. These might be explained by its antioxidant ability as well as its ability to modulate several key inflammatory pathways. Mangiferin has also been shown to be an effective inhibitor of NF-κB signaling pathway. This partially explains its antiinflammatory ability and, additionally, points towards its anticancer potential. The anticancer effects of this compound are just beginning to emerge, and in this comprehensive review, we provide information on what we know about the chemistry and biological effects of mangiferin, which would likely create interest among researchers to design further mechanistic studies in order to better understand and exploit the biological activities of this compound.


[General variable immunologic deficiency with malabsorption syndrome].
Twenty-two patients with general variable immunodeficiency (GVI) and malabsorption syndrome (MS) were followed up for 2-12 years. III degree MS was found in 17 cases. Serum immunoglobulins concentration and T-lymphocyte count were reduced, the latter at the expense of theophylline-resistant and active E-RFC. With casein and milk albumin as the antigens, lymphokine-producing capacity of the mononuclear cells appeared elevated. MS treatment with adjuvant gamma-globulin produced a positive trend in clinical manifestations of the disease, content of T lymphocytes and relevant subpopulations. Long-term results were less favourable: partial compensation with recurrences persisted in 15 patients only. Seven patients died: two of pneumonia, five of cardiac failure and visceral dystrophy. All MS patients are recommended to undergo serum immunoglobulins diagnosis of GVI and in case of its verification to receive life-time gamma-globulin replacement therapy.


Opioid receptor-independent protection of ischemic rat hepatocytes by morphine.
We studied the role of morphine in anoxia/reoxygenation injury to hepatocytes. Overnight cultured rat hepatocytes were incubated in anoxic buffer at pH 6.2 for 4h and reoxygenated at pH 7.4 for 2h to simulate anoxia/reoxygenation. Some hepatocytes were preincubated with 50 microM morphine for 10 min prior to onset of anoxia/reoxygenation. To study the effect of morphine on nitric oxide (NO), hepatocytes were loaded with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM). Changes in NO concentration were assessed with a multi-well fluorescence reader and confocal microscopy. Morphine substantially improved cell viability after reoxygenation and increased NO generation, which was blocked by ATP-sensitive potassium channel blockers. Confocal images revealed that the increase in NO occurred mainly at the cytosol. However, treatment with opioid receptor antagonists did not reverse cytoprotection by morphine. These results indicate that morphine prevents anoxia/reoxygenation injury to hepatocytes. Protective mechanisms are associated with the potassium channels and NO, but are independent of opioid receptor-mediated signaling.


Knowledge, Practice, Compliance, and Barriers toward Ventilator-Associated Pneumonia among Critical Care Nurses in Eastern Mediterranean Region: A Systematic Review.
Ventilator-associated pneumonia (VAP) has been identified as a serious complication among hospitalized patients and is associated with prolonged hospitalizations and increased costs. The purpose of this study was to examine the knowledge, practices, compliance, and barriers related to ventilator-associated pneumonia among critical care nurses in the eastern Mediterranean region. The PRISMA guidelines guided this systematic review. Four electronic databases (EMBASE, MEDLINE (via PubMed), SCOPUS, and Web of Science) were used to find studies that were published from 2000 to October 2021. Knowledge of ventilator-associated pneumonia was the highest outcome measure used in 14 of the 23 studies. The review results confirmed that nurses demonstrated low levels of knowledge of ventilator-associated pneumonia, with 11 studies assessing critical care nurses' compliance with and practice with respect to ventilator-associated pneumonia. Overall, the results showed that most sampled nurses had insufficient levels of compliance with and practices related to ventilator-associated pneumonia. The main barriers reported across the reviewed studies were a lack of education (N = 6), shortage of nursing staff (N = 5), lack of policies and protocols (N = 4), and lack of time (N = 4). The review confirmed the need for comprehensive interventions to improve critical care nurses' knowledge, compliance, and practice toward ventilator-associated pneumonia. Nurse managers must address barriers that impact nurses' levels of knowledge, compliance with, and practices related to ventilator-associated pneumonia.


Force field evaluation for biomolecular simulation: free enthalpies of solvation of polar and apolar compounds in various solvents.
Recently, the GROMOS biomolecular force field parameter set 53A6--which has been parametrized to reproduce experimentally determined free enthalpies of hydration and solvation in cyclohexane of amino acid side-chain analogs--was presented. To investigate the transferability of the new parameter set, we calculated free enthalpies of solvation of a range of polar and apolar compounds in different solvents (methanol, dimethyl sulfoxide (DMSO), acetonitrile, and acetone) from molecular dynamics simulations using the GROMOS 53A6 force field. For methanol and DMSO, parameters were used that are available in the 53A6 parameter set. For acetonitrile, a recently developed model was taken and for acetone, two models available in literature were used. We found that trends in and values for the solvation free enthalpies are in satisfactory agreement with experiment, except for the solvation in acetone for which deviations from experiment can be explained in terms of the properties of the models used.


Comparison of repair techniques for mitral valve prolapse.
Between January 1978 and September 1992, 127 patients with isolated mitral regurgitation due to prolapse underwent mitral valve reconstruction. There were 74 men and 53 women whose mean age was 49.7 years, ranging from 16 to 74 years. Follow up was 99.2% complete and totaled 483.0 patient-years (mean: 3.8 years). One hundred and forty-eight procedures were carried out to repair the prolapses using four types of techniques: (1) leaflet plication in 97 patients; (2) artificial chordal replacement with polytetrafluoroethylene sutures in 30 patients; (3) chordal shortening in 16 patients; and (4) commissural imbrication in five patients. In order to repair the annular dilation, commissural plications were done in 75 and ring prostheses were implanted in 15 patients. There were one hospital and eight late deaths. One (cerebral infarction) of all deaths was related to the reconstructed mitral valve. There were 14 reoperations (11.0%) for recurrent mitral incompetence with a freedom from reoperation of 89.0% at five, and 81.1% at 10 years. There were four cases of thromboembolism (one fatal, three non-fatal) with freedom from thromboembolism of 96.7% at five, and 93.3% at 10 years. No endocarditis or hemorrhagic complications were noted. Linearized incidence of recurrent mitral regurgitation according to repair technique for the prolapse was 1.44%/pty in the leaflet plication series, 1.45%/pty with chordal replacement, 4.37%/pty after chordal shortening and 8.67%/pty following commissural imbrication. The linearized rate of failure in annuloplasty was 2.91%/pty after commissural plication and 1.74%/pty after ring annuloplasty. Statistically significant difference was confirmed only between leaflet plication and chordal shortening.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of the N-terminal secretor domain on YopD translocator function in Yersinia pseudotuberculosis type III secretion.
Type III secretion systems (T3SSs) secrete needle components, pore-forming translocators, and the translocated effectors. In part, effector recognition by a T3SS involves their N-terminal amino acids and their 5' mRNA. To investigate whether similar molecular constraints influence translocator secretion, we scrutinized this region within YopD from Yersinia pseudotuberculosis. Mutations in the 5' end of yopD that resulted in specific disruption of the mRNA sequence did not affect YopD secretion. On the other hand, a few mutations affecting the protein sequence reduced secretion. Translational reporter fusions identified the first five codons as a minimal N-terminal secretion signal and also indicated that the YopD N terminus might be important for yopD translation control. Hybrid proteins in which the N terminus of YopD was exchanged with the equivalent region of the YopE effector or the YopB translocator were also constructed. While the in vitro secretion profile was unaltered, these modified bacteria were all compromised with respect to T3SS activity in the presence of immune cells. Thus, the YopD N terminus does harbor a secretion signal that may also incorporate mechanisms of yopD translation control. This signal tolerates a high degree of variation while still maintaining secretion competence suggestive of inherent structural peculiarities that make it distinct from secretion signals of other T3SS substrates.


[Infectious diseases of drug users in the Czech Republic].
Prevalence of drug users in Czech Republic remains stable in the last years (about 22 to 38 thousands). Two thirds of drug users administer the drug intravenously, what is the most risky way of application. It is also why the number of infectious diseases in that community has not decreased. 435 of drug users were hospitalised between 2002 and 2005 at the Infectious Centre for Drug Users of the Teaching Hospital Motol. Most patients were screened for viral hepatitis and HIV infections, regardless the diagnose during hospitalisation. Patients were hospitalized with the diagnose acute viral hepatitis in 44% (191/436), skin and soft tissue infection in 15% (67/436), chronic hepatitis in 15% (65/436), respiratory infections in 7% (31/436), urogenital infections in 4% (19/436), and sepsis in 4%. Remaining 9% (39/436) of diagnoses represented the less frequent infections. Analysis has shown that 44% of patients acquired hepatitis B and 50% of them are infected with hepatitis C virus. Soft tissue infections, sepsis and infectious endocarditis were caused by sensitive strains of Staphvloco ccus aureus and Streptococcus pyogenes from the group A. Viral hepatitis is the most frequent infectious disease of drug users practising intravenous application in the Czech Republic. Thanks to the extensive vaccination against hepatitis B, the decreased incidence can be expected in the coming years.


Keratitis in Dry Eye Disease and Topical Ciclosporin A.
Tear film alterations in dry eye disease (DED) include reduced tear volume and an increase in inflammatory cytokines. Instability and reduced tear production initiate a vicious cycle where hyperosmolarity, ocular inflammation, and apoptosis may induce damage of the ocular surface including keratitis. Topical cyclosporine (CsA) has been used for the treatment of moderate-to-severe DED; however, previous studies failed to demonstrate its benefits by the European Agency standards. A new formulation of CsA 0.1% has been recently approved in the EU to treat severe keratitis in DED patients. Patients with severe keratitis showed a better improvement after 6 months of treatment with CsA compared with vehicle. HLA-DR expression was significantly reduced by CsA treatment. The clinically significant improvement in keratitis associated with the inflammatory biomarker HLA-DR confirms the efficacy of CsA to improve inflammation and its damaging effect on the ocular surface in DED patients.


Bibliometric Analysis of Research Themes and Trends of the Co-Occurrence of Autism and ADHD.
In recent years, there has been a growing body of research suggesting that ASD and ADHD are two disorders that often co-exist. Despite the rapid development of research, little is known about their etiology, diagnostic markers, and interventions, which has led us to review and summarise the development of the field in the hope that this will provide an opportunity to look for future directions. A bibliometric approach was used to analyse papers in the field of ASD co-morbidities in ADHD on Web of Science from 1991-2022, using CiteSpace and VOSview to map the country/institution, journal, author, co-citation, and keyword networks in the field and to visualise the results. A total of 3284 papers were included, showing an increasing trend in terms of posting trends. Research on co-morbidities of ASD has proven to be mainly focused on universities. The USA (1662) published the most relevant literature in this area, followed by the UK (651) and Sweden (388). Lichtenstein P is the most published author (84), and research into the pathogenesis of ASD co-occurring ADHD and related clinical diagnostics is currently at the forefront of the field. This analysis identifies the most influential institutions and countries, cited journals, and authors in the field of ASD co-morbid ADHD research. The future direction of ASD co-occurring ADHD should be based on improving case identification, discovering the etiological and diagnostic markers of ASD and ADHD, and finding more effective clinical interventions.


Results of a Nutrition and Physical Activity Peer Counseling Intervention among Nontraditional College Students.
Health promotion efforts targeting nontraditional college students (older, part-time enrollment, and working) may be an optimal way to reach large populations that potentially face health disparities. A randomized trial was undertaken to examine the feasibility of a nutrition and physical activity behavioral intervention among nontraditional undergraduate college students at a large urban public university. Over 8 weeks, participants received either (1) a brief tailored feedback report plus three motivational interviewing-based calls from trained peer counselors (intervention; n = 40) or (2) the report only (control; n = 20). Participants mean age was 32 years (SD = 10), 58 % were female, 47 % were racial/ethnic minorities, and 25 % reported receiving public health insurance. Most (78 %) intervention group participants completed at least two of three peer counseling calls. At follow-up, those in the intervention vs. control group self-reported beneficial, but non-statistically significant changes in fruits and vegetables (+0.7 servings/day), sugary drinks (-6.2 oz/day), and fast food visits (-0.2 visits/week). For physical activity, there was a non-statistically significant decrease in moderate-vigorous physical activity (107.2 min/week) in the intervention vs. Overall satisfaction with the program was high, although there were recommendations made for improving the structure and number of calls. Findings indicate that the intervention was feasible with promising effects on nutrition behaviors and the need to better target physical activity behaviors. Future work entails implementation in a larger sample with objectively measured behaviors.


Children's height, health and appetite influence mothers' weaning decisions in rural Senegal.
In many developing countries, breastfed children have a lower nutritional status than those weaned from 12 months of age. Reverse causality, that is, earlier weaning of healthy and well-nourished children, is a possible explanation. Maternal reasons for early and late weaning were investigated in a cohort of 485 rural Senegalese children using structured interviews during two rounds at the ages of 18--28 and 23--33 months, respectively. Length, weight and height were assessed, and dates of weaning were monitored. The mean duration of breastfeeding was 24.1 months (quartiles 21.9 and 26.3). Two-thirds of mothers of breastfed children under 2 stated that they would wean at the age of 2, while for breastfed children aged 2 years, a 'tall and strong' child was the most prevalent criterion. The main reasons for weaning prior to 2 years (N = 244) were that the child ate well from the family plate (60%), that the child was 'tall and strong' (46%) and maternal pregnancy (35%). The main reasons for weaning later than the age of 2 were: a 'little, weak' child (33%), food shortage (25%), illness of the child (24%) and refusal of family food (14%, N = 120). Children breastfed above the age of 2 because they were 'small and weak' had lower mean height-for-age and a greater prevalence of stunting than children breastfed late for other reasons (P < 0.0001). The habit of postponing weaning of stunted children very likely explains why breastfed children have lower height-for-age than weaned children in this setting.


Cranial-bone defects with depression deformity treated with ceramic implants and free-flap transfers.
Hydroxyapatite ceramic has many advantages in the treatment of cranial-bone defects. However, for large skull defects with severe depression deformities, it may be risky to use ceramic implants because an extradural dead space will be left and the overlying scalp will have to be closed under tension. In these cases microvascular free-flap transfers are a good solution. We have treated three patients for large skull defects with severe depression deformities after repeated local infections and several operations or irradiation. A latissimus dorsi myocutaneous flap was combined with a serratus anterior muscle flap to fill the extradural space under the ceramic implant in the first patient. A latissimus dorsi muscle flap was inserted under the ceramic implant in an irradiated site and a combined small serratus anterior muscle flap was used as a monitor in the second patient. A latissimus dorsi myocutaneous flap was used to cover the ceramic implant and fill the scalp defect in the third patient. The follow-up periods varied from 12 to 35 months (mean: 20.7 months). The clinical courses of all three patients were uneventful and no flap was lost. The extradural space can be reduced to some extent by making the ceramic implant slightly flatter or thicker, but in patients with severe depression deformities, whose brain expansion cannot be expected, a muscle flap should be transferred into the space.


Induction of protective immune response in cats by vaccination with feline leukemia virus iscom.
An effective candidate subunit vaccine consisting of the gp 70/85 of feline leukemia virus (FeLV) was prepared by using the immunostimulating complex (iscom) method for the presentation of membrane proteins of enveloped viruses. Two 32-wk-old specific pathogen-free (SPF) cats were immunized with a FeLV iscom vaccine prepared from the supernatant fluid of the FL74 tumor cell line without adjuvant. Both cats developed FeLV serum antibodies, as measured in an enzyme-linked immunosorbent assay (ELISA) and in a virus neutralization test. A proportion of the antibodies were directed to an epitope located on gp70/85, which was shown in competition ELISA with a peroxidase-labeled virus-neutralizing monoclonal antibody to be shared by all three subtypes of FeLV. The protective effect of FeLV iscom was studied by vaccinating six 8-wk-old SPF cats with iscom prepared from cell culture supernatant of another tumor cell line F422, followed by oronasal challenge with 10(6) ffu FeLV-A (strain Glasgow-1). Six unvaccinated cats were also challenged with the same dose of FeLV. The vaccinated cats developed FeLV serum antibodies, some of which were directed to the shared epitope on gp70/85. At 10 wk after challenge, none was viremic, whereas three of the control cats had developed FeLV viremia. The potential of FeLV iscom as a vaccine against FeLV-associated disease in cats, and of iscom vaccines for protection against mammalian retrovirus infections, is discussed.


Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak.
Uncoupling protein (UCP) 1 (UCP1) catalyzes a proton leak in brown adipose tissue (BAT) mitochondria that results in nonshivering thermogenesis (NST), but the extent to which UCP homologs mediate NST in other tissues is controversial. To clarify the role of UCP3 in mediating NST in a hibernating species, we measured Ucp3 expression in skeletal muscle of arctic ground squirrels in one of three activity states (not hibernating, not hibernating and fasted for 48 h, or hibernating) and housed at 5 degrees C or -10 degrees C. We then compared Ucp3 mRNA levels in skeletal muscle with Ucp1 mRNA and UCP1 protein levels in BAT in the same animals. Ucp1 mRNA and UCP1 protein levels were increased on cold exposure and decreased with fasting, with the highest UCP1 levels in thermogenic hibernators. In contrast, Ucp3 mRNA levels were not affected by temperature but were increased 10-fold during fasting and >3-fold during hibernation. UCP3 protein levels were increased nearly fivefold in skeletal muscle mitochondria isolated from fasted squirrels compared with nonhibernators, but proton leak kinetics in the presence of BSA were unchanged. Proton leak in BAT mitochondria also did not differ between fed and fasted animals but did show classical inhibition by the purine nucleotide GDP. Levels of nonesterified fatty acids were highest during hibernation, and tissue temperatures during hibernation were related to Ucp1, but not Ucp3, expression. Taken together, these results do not support a role for UCP3 as a physiologically relevant mediator of NST in muscle.


Prevalence and scalable control of localized networks.
The ability to control network dynamics is essential for ensuring desirable functionality of many technological, biological, and social systems. Such systems often consist of a large number of network elements, and controlling large-scale networks remains challenging because the computation and communication requirements increase prohibitively fast with network size. Here, we introduce a notion of network locality that can be exploited to make the control of networks scalable, even when the dynamics are nonlinear. We show that network locality is captured by an information metric and is almost universally observed across real and model networks. In localized networks, the optimal control actions and system responses are both shown to be necessarily concentrated in small neighborhoods induced by the information metric. This allows us to develop localized algorithms for determining network controllability and optimizing the placement of driver nodes. This also allows us to develop a localized algorithm for designing local feedback controllers that approach the performance of the corresponding best global controllers, while incurring a computational cost orders-of-magnitude lower. We validate the locality, performance, and efficiency of the algorithms in Kuramoto oscillator networks, as well as three large empirical networks: synchronization dynamics in the Eastern US power grid, epidemic spreading mediated by the global air-transportation network, and Alzheimer's disease dynamics in a human brain network. Taken together, our results establish that large networks can be controlled with computation and communication costs comparable to those for small networks.


Detection of polymorphism within leptin gene in Egyptian river buffalo and predict its effects on different molecular levels.
Leptin (LEP) regulates the glucose homeostasis directly and centrally by the regulation of the insulin levels or indirectly by alternation of the levels of the other glucose metabolism regulator hormones. The present investigation studied the polymorphism in LEP gene which is related to fertility in 81 female Egyptian river buffalo. The PCR-RFLP pattern of the gene using the restriction enzyme Eco91I showed that all the animals had monomorphic pattern in the studied gene which consists of CC. A 511-bp fragment from LEP gene was amplified and sequenced. The homology between the amplified LEP gene fragment in buffalo and cattle, sheep, goat, human, and mouse on the nucleotides sequence level was 99, 97, 97, 87, and 79%, respectively, and on the translated amino acids sequence level was 100, 98, 98, 85, and 82%, respectively. Several SNPs were detected; among them, the T27C SNP disrupted an intronic splicing silencer. The A114G, A310G, G263A, and G379A SNPs disrupt exonic splicing enhancers, and the last two SNPs create new exonic splicing enhancers. The A114G, C163A, A211G, G288A, A310G, A322G, G330C, C348T, T360C, and G379A SNPs cause S71G, T87 N, N103S, E129K, E136G, Y140C, E143Q, R149W, S153P, and R159Q amino acids mutations. N103S, E129K, E136G, Y140C, E143Q, and S153P were classified as deleterious mutations. Y140, E143, N103, and R149 were the most conserved among the mutated amino acids. S71G only increased the stability of the leptin protein while the remaining mutations decreased it. Four SNPs were revealed among the tested animals. Twenty-one SNPs were found between the sequenced amplicon and the buffalo records in the Genbank. Some SNPs were predicted to have several effects on different biological processes like mRNA splicing, protein stability, and the gene functions.


Comparative Genomic Analysis Reveals Novel Microcompartment-Associated Metabolic Pathways in the Human Gut Microbiome.
Bacterial microcompartments are self-assembling subcellular structures surrounded by a semipermeable protein shell and found only in bacteria, but not archaea or eukaryotes. The general functions of the bacterial microcompartments are to concentrate enzymes, metabolites, and cofactors for multistep pathways; maintain the cofactor ratio; protect the cell from toxic metabolic intermediates; and protect the encapsulated pathway from unwanted side reactions. The bacterial microcompartments were suggested to play a significant role in organisms of the human gut microbiome, especially for various pathogens. Here, we used a comparative genomics approach to analyze the bacterial microcompartments in 646 individual genomes of organisms commonly found in the human gut microbiome. The bacterial microcompartments were found in 150 (23.2%) analyzed genomes. These microcompartments include previously known ones for the utilization of ethanolamine, 1,2-propanediol, choline, and fucose/rhamnose. Moreover, we reconstructed two novel pathways associated with the bacterial microcompartments. These pathways are catabolic pathways for the utilization of 1-amino-2-propanol/1-amino-2-propanone and xanthine. Remarkably, the xanthine utilization pathway does not demonstrate similarity to previously known microcompartment-associated pathways. Thus, we describe a novel type of bacterial microcompartment.


Hydrogen Sulfide and Carbon Monoxide Tolerance in Bacteria.
Hydrogen sulfide and carbon monoxide share the ability to be beneficial or harmful molecules depending on the concentrations to which organisms are exposed. Interestingly, humans and some bacteria produce small amounts of these compounds. Since several publications have summarized the recent knowledge of its effects in humans, here we have chosen to focus on the role of H2S and CO on microbial physiology. We briefly review the current knowledge on how bacteria produce and use H2S and CO. We address their potential antimicrobial properties when used at higher concentrations, and describe how microbial systems detect and survive toxic levels of H2S and CO. Finally, we highlight their antimicrobial properties against human pathogens when endogenously produced by the host and when released by external chemical donors.


Protection against rotavirus-induced gastroenteritis in a murine model by passively acquired gastrointestinal but not circulating antibodies.
Newborn mice suckled on dams immunized either orally or parenterally with primate rotavirus SA-11 were protected against diarrhea induced by SA-11 virus challenge. Experimental oral administration of milk from orally immunized dams protected suckling mice against challenge; protective activity was detected both in the anti-rotavirus immunoglobulin A (IgA) and IgG fractions, but IgA was more potent in vivo than IgG. Oral administration of milk from parentally immunized dams also protected suckling mice against challenge; in this case, protective activity was detected in the anti-rotavirus IgG fraction. In newborn mice foster-nursed by seronegative dams, circulating rotavirus-specific antibodies in high titer did not protect mice against oral SA-11 virus challenge. It appears that the most effective rotavirus vaccine will be that which induces an efficient production of antibodies active at the intestinal cell surface.


CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum.
CHRNB1 encodes the β subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16 years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2 weeks of life. Furthermore, we note that CHRNB1 variants may be under-recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing.


E. hirae Causing Biliary Tract Infection in a Patient with Cholangiocarcinoma: A Case Report.
E. faecium and E. faecalis are the common species of Enterococcus responsible for the majority of infections. Earlier, species other than the common ones were usually unidentified and reported as Enterococcus species. However, modern equipment, like MALDI-TOF and VITEK2, have been utilitarian, helping us to identify the previously unidentified species. E. hirae is an organism seldom reported to cause human infections. Here, we report a case of a biliary tract infection in a female patient with cholangiocarcinoma caused by E. hirae. A 56-year-old female presented with fever and abdominal pain. Bile aspirated during the ERCP was received in our laboratory. The gram stain of the bile sample revealed abundant polymorphonuclear leucocytes along with gram-positive diplococci. The organism failed to grow on MacConkey agar. On blood agar, non-hemolytic colonies grew. The organism was identified as E. hirae by MALDI-TOF MS. The antibiotic susceptibility performed using VITEK2 revealed it to be resistant to high-level gentamicin and susceptible to all remaining drugs. She was successfully treated with oral ciprofloxacin for the infection. Bile is colonized with bacteria due to obstruction in the biliary tree, leading to cholangitis. This causes bacterial proliferation and translocation of bacteria into the systemic circulation. Our case was resistant to high-level gentamicin, while all previously reported cases were susceptible. The resistant isolates of E. hirae being isolated from cattle and their surroundings amidst the rampant use of antibiotics in livestock can pose a difficult situation for humans. Thus, there should be regulations on antibiotic usage in livestock. Cases like these should be reported and recognized for their potential to cause outbreaks if they remain unreported. Thus, E. hirae, when encountered, should not be ignored but considered a pathogen and reported. The presence of drug-resistant organisms in cattle and their surroundings, their zoonotic potential to cause infections in humans, and the uncontrolled usage of antibiotics in livestock are causes for concern. Thus, we need to be more vigilant regarding it in the future.


Potential Original Drug for Aspergillosis: In Vitro and In Vivo Effects of 1-N,N-Dimethylamino-5-Isocyanonaphthalene (DIMICAN) on Aspergillus fumigatus.
As the recent outbreak of coronavirus disease 2019 (COVID-19) has shown, viral infections are prone to secondary complications like invasive aspergillosis with a high mortality rate, and therefore the development of novel, effective antifungals is of paramount importance. We have previously demonstrated that 1-amino-5-isocyanonaphthalene (ICAN) derivatives are promising original drug candidates against Candida strains (Patent pending), even against fluconazole resistant C. albicans. Consequently, in this study ICANs were tested on Aspergillus fumigatus, an opportunistic pathogen, which is the leading cause of invasive and systematic pulmonary aspergillosis in immunosuppressed, transplanted and cancer- or COVID-19 treated patients. We have tested several N-alkylated ICANs, a well as 1,5-naphthalene-diisocyanide (DIN) with the microdilution method against Aspergillus fumigatus strains. The results revealed that the diisocyanide (DIN) was the most effective with a minimum inhibitory concentration (MIC) value as low as 0.6 µg mL-1 (3.4 µM); however, its practical applicability is limited by its poor water solubility, which needs to be overcome by proper formulation. The other alkylated derivatives also have in vitro and in vivo anti-Aspergillus fumigatus effects. For animal experiments the second most effective derivative 1-N, N-dimethylamino-5-isocyanonaphthalene (DIMICAN, MIC: 7-8 µg mL-1, 36-41 µM) was selected, toxicity tests were made with mice, and then the antifungal effect of DIMICAN was tested in a neutropenic aspergillosis murine model. Compared to amphotericin B (AMB), a well-known antifungal, the antifungal effect of DIMICAN in vivo turned out to be much better (40% vs. 90% survival after eight days), indicating its potential as a clinical drug candidate.


Development and evaluation of loop-mediated isothermal amplification for rapid detection of Haemophilus parasuis.
Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method performed under isothermal conditions and has a high specificity and efficiency. We developed a LAMP assay targeting the 16S rRNA gene for rapid detection of Haemophilus parasuis. The results obtained from testing 31 H. parasuis strains and 28 other bacterial species strains showed that LAMP was as specific as, and more sensitive than, nested PCR. Fifty-five lung samples were collected from 55 healthy pigs. All the samples were negative for H. parasuis by bacterial isolation, nested PCR and LAMP, respectively. In addition, 122 lung samples were collected from 122 pigs with apparent respiratory problems. Sixty-five were positive by bacterial isolation. All the samples that were positive by bacterial isolation were also positive by nested PCR and LAMP. The LAMP assay demonstrated higher sensitivity than nested PCR, picking up 16 additional cases. The LAMP assay also gave a same result compared with the nested PCR when the two assays were used, respectively, to detect H. parasuis from samples obtained from experimentally infected pigs. We concluded that LAMP is a highly sensitive and reliable method for detection of H. parasuis infection.


The emergence, structure and development of ethnic identity during childhood: the case of Roma identity.
This study investigates the emergence, development and structure of ethnic identity during childhood. Forty Roma children living in Greece aged between 2.8 and 11.9 years answered questions about their awareness/recognition of four aspects of their ethnic identity-namely place of habitation, traditional costumes, the Roma language, and early betrothal of children-their identity and their sense of stability and constancy. The study also investigates how the children feel about the abandonment of those four aspects. The evidence from the current data supports the hypothesis that awareness of ethnic identity emerges before the age of 4. Moreover, this study offers direct empirical evidence of the multidimensionality of ethnic identity. A model of three concentric rings is proposed, extending from a core containing the most highly valued aspects of ethnic identity to the outer annulus that comprises the nonpermanent and nonstable aspects of ethnic identity. The aspects in each annulus differ in terms of the development of the sense of stability and constancy and the feelings associated with loss of the aspects in question. Even the youngest participants considered the aspects in the core to be stable and constant as well as emotionally charged; and even the 11-year-olds did not consider the aspects contained in the outer, more fluid annulus as stable and constant aspects of their ethnic identity. The development of an aspect is determined by what the majority of adults in a society, at a particular time in history, consider to be most important.


Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?
Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.


Curcumol Inhibits the Development of Prostate Cancer by miR-125a/STAT3 Axis.
This study aimed to learn the antineoplastic activity of curcumol (Cur) on prostate cancer (PCa) and elucidate its potential molecular mechanism. The proliferation, invasion, and migration of PCa cells (PC3 and 22RV1) were detected by the cell counting kit 8 (CCK8), transwell, and wound healing assay, respectively. The expression of genes and proteins was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB), respectively. The protein expression in tissues and cells was tested through immunohistochemistry (IHC) and immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the level of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The interaction between microRNA125a (miR-125a) and the signal transducer and activator of transcription 3 (STAT3) was confirmed via dual-luciferase reporter assay. Cur effectively restrained the proliferation, invasion, and migration of PC3 and 22RV1 cells. After Cur intervention, miR-125a, miR-375, miR-149, miR-183, and miR-106b were all upregulated in PC3 cells, among which miR-125a was the most significantly upregulated. Dual-luciferase reporter assay combined with qRT-PCR and WB experiments confirmed that miR-125a targeted STAT3. Both in vitro and in vivo, Cur enhanced miR-125a expression and suppressed the activation of the STAT3 pathway in PCa. Also, Cur effectively inhibited the growth of PCa. Cur inhibited the development of PCa by miR-125a/STAT3 axis. This may provide a potential agent for treating PCa.