Bis(4-hy-droxy-phen-yl) 1,4-phenyl-enebiscarbamate.
The title compound, C20H16N2O6 (systematic name: 4-hy-droxy-phenyl N-{4-[(4-hy-droxy-phen-oxy-carbon-yl)amino]-phen-yl}carbamate), contains two urethane groups substituting the central benzene ring in para positions. The mol-ecule is centrosymmetric, and displays a twisted conformation for the three aromatic rings [the dihedral angle between central benzene ring and the urethane group is 33.4 (6)°, and that between the latter and the terminal ring is 65.1 (1)°]. In the crystal, a three-dimensional framework is formed through O-H⋯O and N-H⋯O hydrogen bonds involving the hy-droxy and urethane functional groups, respectively.


Cyanogenic glycosides in Lotus corniculatus : Their effect upon growth, energy budget, and nitrogen utilization of the southern armyworm, Spodoptera eridania.
Two genotypes (one cyanogenic and the other acyanogenic) of birds-foot trefoil, Lotus corniculatus L., were used to study the effects of cyanogenic glycosides in leaf tissues upon a polyphagous herbivore, the southern armyworm, Spodoptera eridania Cram. (Lepidoptera). No differences were observed in consumption rate, assimilation efficiency, utilization of plant biomass, or metabolic costs in terms of expended calories between larvae fed acyanogenic or cyanogenic leaves. Similarly no differences were seen in the nitrogen or caloric utilization efficiencies, or in the nitrogen accumulation rate or growth rate of larvae on cyanogenic versus acyanogenic plants. Larval performance and growth on 20-week old plants was generally poorer than on 4 week old plants, however. This was reflected in slower growth, smaller pupal weights, lower nitrogen utilization efficiencies (N.U.E.) and biomass assimilation efficiencies (A.D.) on both the cyanogenic and acyanogenic plants.Although useful as a deterrent to some herbivores, cyanogenesis does not seem to provide an effective defense against this "adapted" herbivore. This study supports current hypotheses of insect/plant coevolution, and suggests that the metabolic costs of processing cyanogenic plant biomass are small in comparison to those imposed by the nutritional status of the plant leaves.


Association of physical versus affective depressive symptoms with cardiac event-free survival in patients with heart failure.
To determine whether physical depressive symptoms inflate the association between depressive symptoms as measured with the nine-item Patient Health Questionnaire (PHQ-9) and cardiac event-free survival in patients with heart failure (HF). A total of 210 patients with HF were recruited from HF clinics affiliated with two academic medical centers. The PHQ-9 was used to assess levels of depressive symptoms. Cardiac event-free survival data (cardiac death, cardiac hospitalization, or cardiac emergency department visit) were collected for a median follow-up of 360 days. Cox proportional hazards regression analyses were performed separately for physical and affective depressive symptom dimensions of the PHQ-9 to examine predictive ability for time to the first cardiac event. Scores of both physical and affective depressive symptom dimensions of the PHQ-9 predicted time to the first cardiac event in separate unadjusted models. However, scores of the physical depressive symptom dimension did not predict time to the first cardiac events, whereas scores of the affective depressive symptom dimension remained as an independent predictor (hazard ratio = 1.12, 95% confidence interval = 1.03-1.22) after controlling for health status (comorbidities and the New York Heart Association functional class) and clinical and sociodemographic factors. Affective depressive symptoms, not physical depressive symptoms, predicted time to the first cardiac event independent of health status and clinical and sociodemographic characteristics. The use of the full PHQ-9 does not inflate the relationship of depressive symptoms to cardiac event-free survival. Thus, clinicians can use the PHQ-9 to assess depressive symptoms in their patients with HF without concern that the instrument overestimates the relationship between depressive symptoms and outcomes.


Anti-ACTL7a antibodies: a cause of infertility.
To show that antibodies against ACTL7a, a spermatozoon-specific protein, may be a cause of immunologic infertility. Determine the presence of anti-ACTL7a antibodies in infertile blood, raise antibodies against ACTL7a in rabbits, and demonstrate that the in vitro treatment of mouse spermatozoa with infertile sera markedly reduces their fertilizing capacity. Demonstrate that the active immunization of mice with ACTL7a protein reduces fertility. National Research Institute for Family Planning, Beijing, World Health Organization Collaboration Center of Human Reproduction, China. Rabbits, ICR mice. None. Mass spectrometry, indirect immunostaining, spermatozoa agglutination test, and standard fertility assay. The fertilizing potential of mouse spermatozoa was markedly reduced after in vitro treatment with ACTL7a antibody-containing serum from a vasectomized man. Active immunization with ACTL7a significantly reduced the fertility of mice. Anti-ACTL7a antibodies caused the agglutination of mouse and human spermatozoa in vitro. Furthermore, the antibodies were detected in the sera of additional vasectomized men. Anti-ACTL7a antibodies may cause infertility in mice because the in vitro treatment of mouse spermatozoa with ACTL7a antibody-containing serum markedly reduced the fertilizing potential of the spermatozoa. In addition, the active immunization of mice with ACTL7a resulted in significant reductions in fertility.


Weak convergence to isotropic complex [Formula: see text] random measure.
In this paper, we prove that an isotropic complex symmetric α-stable random measure ([Formula: see text]) can be approximated by a complex process constructed by integrals based on the Poisson process with random intensity.


Escin ameliorates inflammation via inhibiting mechanical stretch and chemically induced Piezo1 activation in vascular endothelial cells.
Escin is an active ingredient used in the treatment of phlebitis. However, the pharmacological mechanism of escin remains largely unclear. Here, we aimed to determine the molecular basis for the therapeutic effect of escin. Human umbilical vein endothelial cells (HUVECs) were subjected to shear-stress assays with or without escin. Intracellular Ca2+ levels, inflammatory factors and the activity of NF-κB were measured in endothelial cells (ECs) after mechanical-stretch or Yoda1 activation. Isometric tensions in aortic rings were identified. In addition, murine liver endothelial cells (MLECs) isolated from Piezo1 endothelial specific knockout mice (Piezo1△ EC) were used to explore the role of Piezo1. Our results showed that escin inhibited inflammatory factors, intracellular Ca2+ levels and Yoda1-evoked relaxation of thoracic aorta rings. Cell alignment induced by shear stress was inhibited by escin in HUVECs, and Piezo1 siRNA was used to show that this effect was dependent on Piezo1 channels. Moreover, escin reduced the inflammation and inhibited the activity of NF-κB in ECs with mechanical-stretch, which were insensitive to Piezo1 deletion. SN50, an NF-κB antagonist, significantly inhibited the mechanical stretch-induced inflammatory response. In addition, escin reduced inflammation in ECs subjected to mechanical-stretch, which was insensitive after using NF-κB antagonist. Collectively, our results demonstrate that escin inhibits the mechanical stretch-induced inflammatory response via a Piezo1-mediated NF-κB pathway. This study improves our understanding of a molecular target of escin that mediates its effect on chronic vascular inflammation.


N-Oleoyl glycine, a lipoamino acid, stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte.
Adipose tissue plays a vital role in the development of obesity and related diseases. The aim of the present study was to investigate the effects of N-Oleoyl glycine (OLGly), a lipoamino acid, on 3T3-L1 adipogenesis and to explore the likely mechanisms underlying this process. Lipid accumulation were evaluated using Oil Red O staining and triglyceride content assay. The mRNA expressions of cannabinoid receptors and the protein expressions of adipogenic genes and intracellular signaling pathway were determined by real-time quantitative PCR and western blot, respectively. The results indicated that OLGly itself, but not its degradation products, stimulated lipid accumulation and significantly increased adipogenic genes (PPARγ and aP2), in a dose- and time-dependent manner. Additionally, OLGly markedly increased the mRNA expression of CB1 receptor (CB1R) and the inhibition of CB1R by its antagonist SR141716 abolished the promotive effects of OLGly on lipid accumulation and the protein expression of PPARγ and aP2. Furthermore, OLGly increased the ratio of p-Akt/Akt and p-FoxO1/FoxO1, which could be reversed by SR141716. Moreover, OLGly-induced enhancement of adipogenesis, activation of insulin-mediated Akt signaling pathway and inactivation of FoxO1 were effectively blocked by Wortmannin, a specific PI3K/Akt inhibitor, indicating the essential role of Akt signaling pathway in the process of OLGly-stimulated 3T3-L1 adipogenesis. In conclusion, OLGly, a lipoamino acid, was able to promote 3T3-L1 adipogenesis through the activation of CB1 receptor and the enhancement of insulin-mediated Akt signaling pathway. These findings suggested the potential role of OLGly in increasing insulin sensitivity and suppressing obesity and diabetes.


Problems in diagnosis and management of hypovolaemia in spinal injury.
Thoracic spinal cord injury can result in hypotension from loss of peripheral vascular tone. There may be problems in both diagnosis and management when this is combined with hypovolaemia from haemorrhage. A case is reported that illustrates these difficulties.


The removal of Pluto from the class of planets and homosexuality from the class of psychiatric disorders: a comparison.
We compare astronomers' removal of Pluto from the listing of planets and psychiatrists' removal of homosexuality from the listing of mental disorders. Although the political maneuverings that emerged in both controversies are less than scientifically ideal, we argue that competition for "scientific authority" among competing groups is a normal part of scientific progress. In both cases, a complicated relationship between abstract constructs and evidence made the classification problem thorny.


Predator-induced behavioral defense and its ecological consequences for two calanoid copepods.
We used an automated technique for the observation and quantification of zooplankton swimming behavior to study the behavioral responses of two congeneric, herbivorous, freshwater copepod prey to a copepod predator (Limnocalanus macrurus). One prey, Diaptomus sicilis, often co-occurs with Limnocalanus, while previous studies indicated that the zoogeographic distribution of the second prey, Diaptomus oregonensis, was independent of the predator. We found that in the presence of Limnocalanus, D. sicilis swims more slowly and with less hopping and jumping than D. oregonensis. Diaptomus sicilis is also attacked and consumed by the predator Limnocalanus macrurus less frequently than D. oregonensis. We suggest that the faster, "noisier" swimming of D. oregonensis increases its vulnerability to Limnocalanus. The behavioral defenses to both prey are induced by the presence of the predator, and may represent two different anti-predator strategies, "crypsis" and "avoidance" for D. sicilis and D. oregonensis respectively. In a zoogeographical analysis D. oregonensis occurs at densities below D. sicilis in lakes where Limnocalanus is at elevated abundances, while in "low-predator" lakes the opposite is true. This distribution pattern supports our experimental results, and suggests that D. sicilis is adapted to survive with Limnocalanus, while D. oregonensis is not.


Serum soluble death receptor 5 concentration in patients with chronic hepatitis B is associated with liver damage and viral antigen level.
To measure the levels of serum soluble death receptor 5 (sDR5) in patients with hepatitis B. sDR5 concentration in 60 HBV infected patients and 30 healthy volunteers were measured by ELISA. sDR5 concentration in the HBV infected patients was decreased and correlated with serum ALT, Tbil level, albumin/globulin ratio and HBV antigen level. Decreased serum sDR5 is associated with high level of liver damage and inhibited HBV antigen expression.


Maternal Origins and Haplotype Diversity of Seven Russian Goat Populations Based on the D-loop Sequence Variability.
The territory of modern Russia lies on the crossroads of East and West and covers various geographical environments where diverse groups of local goats originated. In this work, we present the first study on the maternal origin of Russian local goats, including Altai Mountain (n = 9), Dagestan Downy (n = 18), Dagestan Local (n = 12), Dagestan Milk (n = 15), Karachaev (n = 21), Orenburg (n = 10), and Soviet Mohair (n = 7) breeds, based on 715 bp D-loop mitochondrial DNA (mtDNA) sequences. Saanen goats (n = 5) were used for comparison. Our findings reveal a high haplotype (HD = 0.843-1.000) and nucleotide diversity (π = 0.0112-0.0261). A total of 59 haplotypes were determined in the Russian goat breeds, in which all differed from the haplotypes of the Saanen goats. The haplotypes identified in Altai Mountain, Orenburg, Soviet Mohair, and Saanen goats were breed specific. Most haplotypes (56 of 59) were clustered together with samples belonging to haplogroup A, which was in accordance with the global genetic pattern of maternal origin seen in most goats worldwide. The haplotypes that were grouped together with rare haplogroups D and G were found in the Altai Mountain breed and haplogroup C was detected in the Soviet Mohair breed. Thus, our findings revealed that local goats might have been brought to Russia via various migration routes. In addition, haplotype sharing was found in aboriginal goat populations from overlapping regions, which might be useful information for their official recognition status.


Toxicity of cisplatin and hydroxymalonatodiammine platinum (II) towards mouse bone marrow and B16 melanoma in relation to DNA binding in vivo.
The antitumour selectivity of cisplatin and hydroxymalonatodiammine platinum II (Pt[OHmal(NH3)2]), a second generation platinum drug, was evaluated in C57B1/Cbi mice bearing advanced intramuscular B16 melanoma. At maximally tolerated doses, Pt[OHmal(NH3)2] produced greater inhibition of growth of the advanced B16 melanoma than did cisplatin. Comparison of dose-response curves for survival of B16 lung colony-forming cells and bone marrow stem cells treated in vivo indicated that selective killing of B16 cells was achieved with Pt[OHmal(NH3)2], whereas cisplatin was relatively nonselective. The extent of reaction of platinum with DNA at doses producing measurable levels of survival in tumour and marrow in vivo was similar to values previously observed in cultured cells treated with cisplatin in vitro. Studies of the amount of platinum bound to DNA in tumour and marrow following administration of the two drugs revealed that the improved selectivity of Pt[OHmal(NH3)2] was associated with a selective increase in the amount of platinum bound to tumour DNA, relative to cisplatin. In addition, platinum lesions produced in DNA by Pt[OHmal(NH3)2] appeared to be more effective in producing tumour cell killing than those produced by cisplatin. No significant excision of total DNA-bound platinum from tumour was observed up to 48 h after administration of either drug.


The health-related quality of life of lung cancer patients with EGFR-TKI-related skin adverse drug reactions and its relationship with coping style and self-management.
The status and associated factors of the health-related quality of life of non-small-cell lung cancer (NSCLC) patients under targeted anti-cancer therapy have not been investigated. Self-management and coping style have been proven to be closely related to patients' health-related quality of life. Based on these observations, this study was designed to firstly assess the status of health-related quality of life, and then explore the relationships among coping styles, self-management, and health-related quality of life of NSCLC patients with skin adverse drug reactions under targeted therapy. We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions under targeted therapy in cancer clinics of three hospitals in China between May 2020 and May 2021. Structured questionnaires, including the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18, Cancer Patient Self-management Evaluation Scale, and Medical Coping Modes Questionnaire, were used to collect data. Relationships among coping style, self-management, and health-related quality of life were identified by Pearson correlation analysis and a multiple linear regression algorithm. The total score of health-related quality of life was 46 ± 12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. Health-related quality of life was positively correlated with self-management (r = 0.785, P < 0.01) and facing (r = 0.807, P < 0.01) and negatively correlated with yield (r = - 0.718, P < 0.01), avoidance (r = - 0.711, P < 0.01), and the severity of skin adverse reactions (r = - 0.722, P = 0.000). Via multiple linear regression analysis, we identified some significant factors associated with health-related quality of life, including age, education level, combination of medicine, Charlson Comorbidity Index, stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy, and self-management (P < 0.05). NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised health-related quality of life. The critical factors that were associated with the status of health-related quality of life were age, education level, comorbidity, the combinatorial application of drugs, stage of disease, self-management, and coping styles.


Diaphragm Function Assessment During Spontaneous Breathing Trial in Patients with Neuromuscular Diseases.
The optimal time to discontinue patients from mechanical ventilation is critical as premature discontinuation as well as delayed weaning can result in complications. The literature on diaphragm function assessment during the weaning process in the intriguing subpopulation of critically ill neuromuscular disease patients is lacking. Patients with neuromuscular diseases, on mechanical ventilation for more than 7 days, and who were ready for weaning were studied. During multiple T-piece trials over days, diaphragm function using ultrasound and diaphragm electrical activity (Edi peaks using NAVA catheter) was measured every 30 min till a successful 2 h weaning. A total of 18 patients were screened for eligibility over 5-month period and eight patients fulfilled the inclusion criteria. Sixty-three data points in these 8 subjects were available for analysis. A successful breathing trial was predicted by Edi reduction (1.22 μV for every 30 min increase in weaning duration; 0.69 μV for every day of weaning) and increase in diaphragm excursion (2.81 mm for every 30 min increase in weaning duration; 2.18 mm for every day of weaning). The Edi and diaphragm excursion changes can be used as additional objective tools in the decision-making of the weaning trials in neuromuscular disease.


Smart plastic antibody material (SPAM) tailored on disposable screen printed electrodes for protein recognition: application to myoglobin detection.
This work introduces two major changes to the conventional protocol for designing plastic antibodies: (i) the imprinted sites were created with charged monomers while the surrounding environment was tailored using neutral material; and (ii) the protein was removed from its imprinted site by means of a protease, aiming at preserving the polymeric network of the plastic antibody. To our knowledge, these approaches were never presented before and the resulting material was named here as smart plastic antibody material (SPAM). As proof of concept, SPAM was tailored on top of disposable gold-screen printed electrodes (Au-SPE), following a bottom-up approach, for targeting myoglobin (Myo) in a point-of-care context. The existence of imprinted sites was checked by comparing a SPAM modified surface to a negative control, consisting of similar material where the template was omitted from the procedure and called non-imprinted materials (NIMs). All stages of the creation of the SPAM and NIM on the Au layer were followed by both electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). AFM imaging was also performed to characterize the topography of the surface. There are two major reasons supporting the fact that plastic antibodies were effectively designed by the above approach: (i) they were visualized for the first time by AFM, being present only in the SPAM network; and (ii) only the SPAM material was able to rebind to the target protein and produce a linear electrical response against EIS and square wave voltammetry (SWV) assays, with NIMs showing a similar-to-random behavior. The SPAM/Au-SPE devices displayed linear responses to Myo in EIS and SWV assays down to 3.5 μg/mL and 0.58 μg/mL, respectively, with detection limits of 1.5 and 0.28 μg/mL. SPAM materials also showed negligible interference from troponin T (TnT), bovine serum albumin (BSA) and urea under SWV assays, showing promising results for point-of-care applications when applied to spiked biological fluids.


Tuberous sclerosis complex associated with heterotopic ossification in a young girl.
Tuberous sclerosis complex (TSC) is a multisystem disorder resulting in hamartomatous lesions. Despite diverse manifestations, skeletal muscular comorbidity is rarely reported in TSC. We report a 2-year-old girl with TSC who suffered from multiple subcutaneous masses over the paraspinal and bilateral scapular areas, which caused disabling pain on any passive movement. Three-dimensional computed tomography scanning revealed multiple calcifications that were consequently diagnosed as fibrodysplasia ossificans progressiva. Such imaging features should be evaluated cautiously to avoid unnecessary surgical intervention and biopsy that may worsen the condition.


A case report of exudative retinal detachment derived from orbital cellulitis in mainland China.
Orbital cellulitis is a rare cause of exudative retinal detachment. Hereby, we aimed to report the first case of exudative retinal detachment derived from orbital cellulitis in mainland China. A 16-year-old girl developed severe left orbital cellulitis in 4 days. Two exudative retinal detachment lesions were presented in her left eye retina. Blood cultures were performed which identified Staphylococcus aureus. However, the cause for the orbital cellulitis was not idenitfied in this patient. Systemic application of antibiotics together with topical antibiotics and corticosteroid was effective to the improvement of orbital cellulitis and resolution of exudative retinal detachment. The treatment of such clinical condition is that of orbital cellulitis in general. The exudative retinal detachment can resolve to a great extent upon cure of the underlying disease, followed by visual acuity recovery.


Early-onset Alzheimer's disease: an analysis of CT findings.
Brain computed tomographic scans of 60 patients with early-onset Alzheimer's disease (mean age, 60.7 years) were compared with those of age- and sex-matched control subjects. Computed tomographic analysis included standard ventricular measurements as well as subjective ratings of ventricular and sulcal size. These indices were correlated with the results of a battery of neuropsychological tests and electroencephalographic findings. Linear measurements of ventricular size were significantly greater in the patients with Alzheimer's disease than in the age-matched control group (p less than 0.0005). Using subjective appraisal of ventricular and sulcal size, the neuroradiologist noted abnormalities significantly more often in patients than in controls (p less than 0.0005). Linear measurements of ventricular size correlated significantly (p less than 0.05) with the severity of aphasia and dementia and the presence of electroencephalographic abnormalities. There was, however, no correlation between the subjective judgment of cortical atrophy and the degree of impairment as measured by neuropsychological tests. The findings in this study demonstrate the usefulness of computed tomographic imaging in Alzheimer's disease of early onset.


Analytical versus clinical sensitivity and specificity in pregnancy testing.
A typical urine pregnancy test with the enzyme-linked immunoassay for human chorionic gonadotropin (Tandem Icon human chorionic gonadotropin) was performed as was a qualitative serum radioimmunoassay for human chorionic gonadotropin when the positive cutoff for the latter was set at 30 IU/L. There was 99.5% concordance between the two methods when performed on 871 simultaneous urine and serum specimens. Although the serum radioimmunoassay can detect levels of human chorionic gonadotropin as low as 10 IU/L, in this study the majority of patients with serum levels between 10 and 30 IU/L were not pregnant on clinical follow-up. Of nine patients with adequate clinical follow-up, a negative urine pregnancy test result, and a serum human chorionic gonadotropin level between 10 and 30 IU/L, only one proved to be pregnant. The Tandem Icon human chorionic gonadotropin urine test is sufficient for routine pregnancy testing and to rule out the need for immediate intervention in cases of ectopic pregnancy.


Distinct nuclear organization, DNA methylation pattern and cytokinin distribution mark juvenile, juvenile-like and adult vegetative apical meristems in peach (Prunus persica (L.) Batsch).
Chromatin organization, nuclear DNA methylation and endogenous zeatin localization were investigated in shoot apical meristems (SAM) during juvenile and adult phases of peach (Prunus persica (L.) Batsch). The aim was to examine the extent to which these parameters could discriminate the juvenile and adult SAMs. Seedlings (juvenile, cannot flower), basal shoots (called juvenile-like, because they exhibit juvenile macroscopic traits) and apical shoots (competent to form flowers) of adult plants were chosen. Nuclear chromatin exhibited chromocentres that were peripherally distributed in SAMs of juvenile and juvenile-like shoots, but were diffusely spread in those of adult shoots. These patterns coincided with a peripheral labelling of DNA methylation in juvenile and juvenile-like meristem nuclei versus a diffuse labelling pattern in adult meristem nuclei. During vegetative growth (from March to June), the level of nuclear DNA methylation was higher in adult meristems than in juvenile and juvenile-like ones. The immunolocalization of zeatin in juvenile SAM was in the subapical region, but adult meristems exhibited a widespread localization or a signal confined within the boundaries of the central zone. The extent to which the acquisition of a strongly zonated pattern of these parameters as markers of floral competence in adult SAMs is discussed.


Low prevalence of bloodstream infection and high blood culture contamination rates in patients with COVID-19.
In the management of COVID-19, knowledge is lacking on the frequency of secondary bacterial infections and on how empirical antibiotic therapy should be used. In the present study, we aimed to compare blood culture (BC) results of a COVID-19 patient cohort with two cohorts of patients without detected COVID-19. Using a retrospective cohort study design of patients subjected to BC in six tertiary care hospitals, SARS-CoV-2 positive patients from March 1 to April 30 in 2020 (COVID-19 group) were compared to patients without confirmed SARS-CoV-2 during the same period (control group-2020) and with patients sampled March 1 to April 30 in 2019 (control group-2019). The outcomes studied were proportion of BC positivity, clinically relevant growth, and contaminant growth. In total 15,103 patients and 17,865 BC episodes were studied. Clinically relevant growth was detected in 197/3,027 (6.5%) BC episodes in the COVID-19 group compared to 717/6,663 (10.8%) in control group-2020 (p<0.0001) and 850/8,175 (10.4%) in control group-2019 (p<0.0001). Contamination was present in 255/3,027 (8.4%) BC episodes in the COVID-19 group compared to 330/6,663 (5.0%) in control group-2020 (p<0.0001) and 354/8,175 (4.3%) in control group-2019 (p<0.0001). In COVID-19 patients, the prevalence of bloodstream bacterial infection is low and the contamination rate of BC is high. This knowledge should influence guidelines regarding blood culture sampling and empirical antibiotic therapy in COVID-19 patients.


Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study.
The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996-March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. Since receiving marketing authorization (February 21, 1996), ~647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ~31 000) is in line with the incidence observed with other four-factor PCCs. In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.


Is sleep nasendoscopy a valuable adjunct to clinical examination in the evaluation of upper airway obstruction?
The objective of the study is to assess the correlation between outpatient department (OPD) assessment and sleep nasendoscopy (SNE) in treatment planning for sleep related breathing disorders. The study design includes a blinded, cohort study comparing the treatment prediction based on OPD clinical evaluation with SNE in consecutive, adult patients by a single clinician with a specialist interest in snoring related disorders. Patients with moderate to severe obstructive sleep apnoea and those who had undergone previous treatment were excluded. The study was conducted in Royal National Throat, Nose and Ear Hospital, London and Queen's Hospital, Romford. Ninety-four patients were recruited as participants for the study. The main outcome measures include site of obstruction and treatment planning. The results show no significant correlation between the two groups with SNE recommending less surgical intervention and a choice of surgical and non-surgical management in greater number of patients. In conclusion, even in experienced hands, clinical prediction is significantly modified by SNE findings. The addition of SNE to the diagnostic pathway, to assess the three-dimensional dynamic anatomy of the upper airway, provides a valuable adjunct to the OPD assessment of upper airway collapse. This affords the clinician a greater accuracy of diagnosis and the patient a more focussed management strategy with increased choice of modality of treatment.


Gate-Tunable Magnetism via Resonant Se-Vacancy Levels in WSe2.
The confined defects in 2D van der Waals (vdW)-layered semiconductors can be easily tailored using charge doping, strain, or an electric field. Nevertheless, gate-tunable magnetic order via intrinsic defects has been rarely observed to date. Herein, a gate-tunable magnetic order via resonant Se vacancies in WSe2 is demonstrated. The Se-vacancy states are probed via photocurrent measurements with gating to convert unoccupied states to partially occupied states associated with photo-excited carrier recombination. The magneto-photoresistance hysteresis is modulated by gating, which is consistent with the density functional calculations. The two energy levels associated with Se vacancies split with increasing laser power, owing to the robust Coulomb interaction and strong spin-orbit coupling. The findings offer a new approach for controlling the magnetic properties of defects in optoelectronic and spintronic devices using vdW-layered semiconductors.


BEG spin-1 model with random exchange magnetic interactions for spin-crossover solids.
We have investigated magnetic phase diagrams of spin-crossover (SCO) solids throughout the Blume-Emery-Griffiths spin-1 model where the spin states ±1 and 0 are associated to high-spin state and low-spin states respectively. In the present work, the quadrupolar interaction,K, parameter depends linearly on temperature and accounts for the role of the lattice phonons in the elastic interactions between the SCO units. Magnetic interactions are randomly distributed in the system and are controlled by a factorγ=Jij/Ksuch that forγ = 0 (Jij=0), magnetic ordering is not expected. The crystal-field that acts on SCO sites depends both on the ligand-field strength and the degeneracy ratio between HS and LS states as in some previous works. The system is also under the effect of a random local magnetic fieldhiacting on each sitei. The model is solved using a homogeneous mean field theory. Our investigations reveal the occurrence of thermally-induced gradual, and first-order spin-transitions by varying the model parameters. At vicinity of first-order transition, various types of isothermal magnetic hysteresis loops are obtained and their corresponding coercive field and loop patterns are discussed as function of temperature.


The d10 route to dye-sensitized solar cells: step-wise assembly of zinc(II) photosensitizers on TiO2 surfaces.
Dye-sensitized solar cells have been assembled using a sequential approach: a TiO(2) surface was functionalized with an anchoring ligand, followed by metallation with Zn(OAc)(2) or ZnCl(2), and subsequent capping with a chromophore functionalized 2,2':6',2''-terpyridine; the DSCs exhibit surprisingly good efficiencies confirming the effectiveness of the new strategy for zinc-based DSC fabrication.


[Crystal structure and photoluminescence studies of ZnO nanocrystals doped with Eu3+ ions].
The ZnO: Eu3+ crystal was prepared via coprecipitation with the starting materials Zn(OOCCH3)2 x 2H2O, Eu2O3 and NaOH. The X-ray diffraction patterns show that the samples are hexagonal wurtzite structure, No diffraction peaks from europium oxides are detectable. Comparing the ZnO and ZnO : Eu3+ Raman spectra, the new local vibrational modes were observed in ZnO : Eu3+. These phenomena show that Eu3+ ions have entered the lattice by doping. The SEM analysis exhibits that ZnO nanoparticles prepared by coprecipitation become smaller with Eu3+ doping. The excitation and emission spectra of ZnO : Eu3+ sample present a efficient energy transfer process between ZnO and Eu3+ ions.


Occluded Brescia-cimino hemodialysis fistulas: endovascular treatment with both brachial arterial and venous access using the pull-through technique.
We retrospectively evaluated the usefulness of both arterial and venous access with the pull-through technique in endovascular treatment of totally occluded Brescia-Cimino fistulas. We treated 26 patients (17 men, 9 women; age range 43-82 years, mean age 66 years) with occluded Brescia-Cimino fistulas. First, the occluded segment was traversed from the antegrade brachial arterial access using a microcatheter-guidewire system. Second, the vein was retrogradely punctured after confirmation of all diseased segments, and a 0.014- or 0.016-inch guidewire was pulled through the venous access when the occluded segment was long. All interventions including thrombolysis, thromboaspiration, angioplasty, and stent placement were performed via the venous access. The occlusion was successfully crossed via the brachial arterial access in 23 patients (88%). In 2 patients it was done from the venous approach. In the remaining patient it was not possible to traverse the occluded segment. The pull-through technique was successful in all 19 attempts. Clinical success was achieved in 96%, the primary patency rates at 6, 12, and 18 months were 83%, 78%, and 69%, the primary assisted patency rates were 92%, 92%, and 72%, and the secondary patency rates were 92%, 92%, and 92%, respectively. Minor complications in 5 patients included venous perforation in 2 (8%), venous rupture in 1 (4%), and regional hematoma in 2 (8%). Our study suggests that endovascular treatments with both arterial and venous access using the pull-through technique are highly effective in restoring function in totally occluded Brescia-Cimino fistulas.


Purification and characterization of a recombinant beta-galactosidase with transgalactosylation activity from Bifidobacterium infantis HL96.
A beta-galactosidase isoenzyme, beta-Gall, from Bifidobacterium infantis HL96, was expressed in Escherichia coli and purified to homogeneity. The molecular mass of the beta-Gall subunit was estimated to be 115 kDa by SDS-PAGE. The enzyme appeared to be a tetramer, with a molecular weight of about 470 kDa by native PAGE. The optimum temperature and pH for o-nitrophenyl-beta-D-galactopyranoside (ONPG) and lactose were 60 degrees C, pH 7.5, and 50 degrees C, pH 7.5, respectively. The enzyme was stable over a pH range of 5.0-8.5, and remained active for more than 80 min at pH 7.0, 50 degrees C. The enzyme activity was significantly increased by reducing agents. Maximum activity required the presence of both Na+ and K+, at a concentration of 10 mM. The enzyme was strongly inhibited by p-chloromercuribenzoic acid, divalent metal cations, and Cr3+, and to a lesser extent by EDTA and urea. The hydrolytic activity using lactose as a substrate was significantly inhibited by galactose. The Km, and Vmax values for ONPG and lactose were 2.6 mM, 262 U/mg, and 73.8 mM, 1.28 U/mg, respectively. beta-Gall possesses strong transgalactosylation activity. The production rate of galactooligosaccharides from 20% lactose at 30 and 60 degrees C was 120 mg/ml, and this rate increased to 190 mg/ml when 30% lactose was used.


Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa.
Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.


[Association of Parry-Romberg syndrome and paroxymal kinesigenic dyskinesia].
Parry-Romberg syndrome is a rare entity of unknown etiology, characterized by hemifacial or hemibody atrophy affecting subcutaneous tissues. Its main clinical manifestations are neurological, ocular and dermatological. Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of choreic/dystonic movements triggered by sudden movements and improved by antiepileptic drugs particularly carbamazepine. It can be sporadic or familial with an autosomal dominant inheritance. Little is known about the pathophysiology of PKD, although a channelopathy is thought likely. The association of these two diseases is rare. Over three years, a 42-year-old patient progressively developed left hemiatrophy. Since age 14, he presented paroxysmal dystonic disorders of the limbs triggered by sudden movements and controlled by carbamazepine. The diagnosis of PKD associated with Parry-Romberg syndrome was established. Investigations revealed immunologic and diffuse electrophysiological abnormalities (EEG and EMG). PKD associated with Parry-Romberg syndrome is very rare but does not appear to be fortuitous. It suggests a common mechanism via an underlying channelopathy or dysimmune disorder.


The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer.
The aim of this study was to investigate the contribution of cathepsin B and cystatin C to the mechanisms of invasion by ovarian cancer. Using surgical materials from patients with ovarian cancer, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis were performed using antibodies against cathepsin B or cystatin C. Serum levels of cathepsin B and cystatin C in patients with benign and malignant ovarian lesions were determined by enzyme-linked immunosorbent assay (ELISA). An invasion assay using an ovarian cancer cell line was performed by addition of cystatin C or specific inhibitors of cathepsin B. While immunohistochemical staining of cathepsin B and cystatin C was evident in cancer cells and associated stromal tissue, this was not the case in benign tumors. The malignancies were also found to be positive for cathepsin B and cystatin C by SDS-PAGE and Western blotting analysis. No significant difference in serum cathepsin B levels was observed between patients with benign and malignant disease. However, the concentration of cystatin C in cases with ovarian cancer was significantly higher in benign cases (P<0.0001) and in healthy controls (P<0.0001). Invasion by cancer cells was dose-dependently suppressed by cystatin C and cathepsin B inhibitors. The results provided convincing evidence that cathepsin B and cystatin C may contribute to the mechanisms of invasion of ovarian cancer.


HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.
Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Herein we show using an autochthonous ccRCC model that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are required for the clear cell phenotype. Transcriptomic and proteomic analyses reveal that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2α-deficient tumours are characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlate with altered immune microenvironments in human ccRCC. These studies reveal an oncogenic role of HIF-1α in ccRCC initiation and suggest that alterations in the balance of HIF-1α and HIF-2α activities can affect different aspects of ccRCC biology and disease aggressiveness.


Online seizure first aid certification program is an effective means of improving student knowledge and self efficacy surrounding epilepsy.
Epilepsy is a neurological disorder, characterized by recurring seizures, affecting more than 3.4 million adults and children throughout the United States. Still, there are sizable gaps in awareness and knowledge of this disorder, and persistent misunderstandings and stigmas surrounding epilepsy and seizure first aid (SFA) pose a risk to those living with this condition. The Epilepsy Foundation, with support from the Centers for Disease Control and Prevention (CDC), has developed programs to address the issue of insufficient public education and awareness surrounding epilepsy. One of these programs is a free, accessible online Seizure Recognition and First Aid Certification program, established in 2021. We aimed to evaluate the effectiveness of the Epilepsy Foundation's online Seizure Recognition and First Aid Certification program in improving student knowledge of epilepsy and appropriate bystander-intervention methods to assist a person experiencing a seizure. The Epilepsy Foundation's online Seizure Recognition and First Aid Certification course evaluates student performance via a 16-question knowledge assessment and six question self-efficacy assessment provided both before and after completion of the course. Pre- and post-course scores of students who enrolled between December of 2021 and September of 2022 were collected. Average score improvement was evaluated via the difference in pre-course and post-course first-attempt scores. Statistical significance was evaluated using paired sample, two-tailed t-tests of pre-course and post-course scores. Average pre-course knowledge score was 74.33% (n = 10,371, σ2 = 3.04%), post-course score was 88.04% (n = 10,371, σ2 = 0.83%), and score difference was 13.71% (p < 0.001). Average pre-course self-efficacy score was 63.44% (n = 8,046, σ2 = 4.71%), post-course score was 87.08% (n = 8,046, σ2 = 1.68%), and score difference was 23.64% (p < 0.001). We found a significant increase in knowledge and self-efficacy assessment scores after students completed the online Seizure Recognition and First Aid Certification course, suggesting that the program is an effective method of improving the understanding of epilepsy and bystander interventions to assist a person who is experiencing a seizure. In the future, awareness should continue to be promoted through SFA training programs and improving accessibility to such programs so that the risks associated with experiencing a seizure without receiving assistance are reduced for people living with epilepsy.


Effects of Yogic Interventions on Patients Diagnosed With Cardiac Diseases. A Systematic Review and Meta-Analysis.
Presently, evidence-based research studies on the efficacy of complimentary therapies like yoga for patients with different cardiac diseases are limited and conflicting. The objective of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on yogic interventions compared with usual care or non-pharmacological treatment in patients diagnosed with cardiac diseases. We conducted an electronic search of literature published from 2006 to May 2021 through five databases. PRISMA statement was used to develop and report a systematic review and meta-analysis protocol. Sixteen RCTs were included in the systematic review and 11 RCTs were used for meta-analysis. Outcome measures were blood pressure, lipid profile, and psychosocial measures. The Cochrane collaboration tool was used to assess bias risk. The results show that yogic interventions resulted in significant reduction in systolic (d = 046; 95% CI.08-0.84; I2 = 81.86%) and diastolic blood pressures (d = 0.56; 95% CI.13-0.99, I2 = 84.84%). A medium statistically significant increase in HDL (d =0.67; 95% CI 0 to 1.33; I2 79.7%) and a low but significant effect on LDL (d = 0.23; 95% CI -0.08-0.54; I2 32.61%), total cholesterol (d =0.28; 95% CI -0.14-0.7; I2 63.72%), and triglycerides (d = 0.43; 95% CI -0.1-0.97; I2 76.64%) were observed. Pooled effect sizes showed a medium to low statistically significant effect on psychosocial indicators viz., QoL, stress, anxiety, and depression. The meta-analysis found strong evidence of effectiveness of yogic interventions on lipid profile, blood pressure, and psychosocial outcomes in patients with diagnosed cardiac diseases.


Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.
In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.


Unilateral suppression of P/N13' potential amplitude in young patients with persistent numbness due to cervical monoradiculopathy. A case-control study.
The utility of Dermatomal Somatosensory Evoked Potentials (DSEPs) in the diagnostic workup of suspected cervical monoradiculopathy has been limited by significant overlap between measurements obtained from affected versus unaffected roots. In a case-control study, we explored whether, under certain conditions, asymmetry in DSEP parameters may offer significant help in the diagnosis of monoradiculopathy. DSEPs were obtained bilaterally from patients with persistent (age range 33-55, n = 10) or intermittent (age range 31-55, n = 7) unilateral sensory symptoms of less than one month duration due to MRI-confirmed cervical monoradiculopathy. DSEPs were also obtained bilaterally from aged-matched asymptomatic volunteers (age range 31-54, n = 8) and older asymptomatic volunteers (age range 57-77, n = 8). Amplitude and latency of the P/N13' potential (negative peak at 13 ms) were measured. In all ten patients with persistent symptoms, the P/N13' amplitude ratio, defined as P/N13' amplitude on the symptomatic side divided by P/N13' amplitude on the contralateral asymptomatic side, ranged between 0.0 and 0.50 (unilateral suppression). In all seven patients with intermittent symptoms, P/N13' amplitude ratios ranged between 0.60 and 1.00. In all age-matched asymptomatic controls, P/N13' amplitude ratio (side with lower divided by side with higher amplitude) was always at least 0.80. Among older asymptomatic subjects, DSEPs had inconsistent characteristics. Cervical monoradiculopathy with persistent numbness in young patients (aged up to 55 years) is very strongly associated with unilateral suppression of P/N13' DSEP amplitude. No significant asymmetry is observed in cases of monoradiculopathy with intermittent numbness. In young patients with unilateral upper extremity persistent sensory complaints, DSEP amplitude asymmetry, as quantified by the P/N13' ratio, may offer significant help in the diagnosis of monoradiculopathy.


Cloning Endangered Felids by Interspecies Somatic Cell Nuclear Transfer.
In 2003, the first wild felid was produced by interspecies somatic cell nuclear transfer. Since then other wild felid clone offspring have been produced by using the same technique with minor modifications. This chapter describes detailed protocols used in our laboratory for (1) the isolation, culture, and preparation of fibroblast cells as donor nucleus, and (2) embryo reconstruction with domestic cat enucleated oocytes to produce cloned embryos that develop to the blastocyst stage in vitro and, after transfer into synchronized recipients, establish successful pregnancies.


Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson's disease: a case report.
Spinal cord stimulation (SCS) has recently been reported to be effective for truncal postural abnormalities such as camptocormia and Pisa syndrome in Parkinson's disease. In this case report, we describe a case of a woman with Parkinson's disease in whom SCS was effective for painful camptocormia with Pisa syndrome. A 65-year-old woman was admitted to our hospital because of painful camptocormia. She had noticed resting tremor in the left upper limb and aprosody at 48 years of age. She was diagnosed as having Parkinson's disease (Hoehn & Yahr stage 1) at 53 years of age. Cabergoline was started during that same year, with subsequent addition of selegiline hydrochloride; the symptoms of parkinsonism disappeared. Wearing-off occurred when she was 57 years old, 3 years after starting carbidopa/levodopa, and truncal postural abnormalities-painful camptocormia with Pisa syndrome to the right-appeared at 58 years of age. These symptoms worsened despite adjustment of her oral medications, and deep brain stimulation (DBS) was performed when she was 60 years old. The truncal postural abnormalities improved after DBS, and she could travel abroad at 61 years of age. However, from 62 years of age, painful camptocormia with Pisa syndrome to the right reappeared. The pain was unsuccessfully treated with oral analgesics, radiofrequency coagulation of the dorsal and medial branches of the lumbar spinal nerve, and lumbar epidural block. Finally, SCS was performed for the pain relief. The pain disappeared immediately after SCS and her posture then gradually improved. Unified Parkinson's Disease Rating Scale score improved from 48 to 34 points and Timed Up and Go Test improved from 15 s to 7 s after SCS. This case suggests that SCS may be effective for improving painful truncal postural abnormalities and motor complications of Parkinson's disease. Pain relief or a direct effect on the central nervous system by SCS was considered to explain the alleviation of these symptoms.


Biological hydrogen production from palm oil mill effluent (POME) by anaerobic consortia and Clostridium beijerinckii.
Palm oil mill effluent (POME) was tested as a substrate to produce hydrogen by dark fermentation. Two microbial consortia and a pure culture of Clostridium beijerinckii (ATCC 8260) were cultured anaerobically in raw, diluted and hydrolyzed POME to compare biohydrogen production yields in all three media. Experiments were done in 15 mL Hungate tubes containing 5 mL of medium and 1 mL of inoculum. When Clostridium beijerinckii was cultivated at 30 °C in the hydrolyzed POME (P003), containing 7.5 g/L of sucrose, during 8 days of fermentation and 20 % of the inoculum, the maximum biohydrogen production yield was 4.62 LH2/Lmed. Consortium C3 also showed the best production in hydrolyzed POME while consortium C6 achieved its maximum production in raw POME. This effluent is a potential substrate for biohydrogen production.


Sex differences in seasonal variations in P300.
Previous reports of seasonal variations in P300 were based on cross-sectional observations of subjects tested at different times of the year. In this study, we tested three groups of subjects in each of two seasons: winter and spring, spring and summer, and summer and winter. We found winter or spring maxima in auditory and visual P300 and visual slow wave. This pattern of results, with the amplitude of P300 being inversely related to the amount of sunlight in a season, supports the hypothesis that the allocation of processing resources varies across the seasons. Our results also suggest a trend for an increased sensitivity of women, as compared with men, to seasonal influences on P300. Although our findings do not provide strong evidence that P300 varies systematically as a function of season, seasonal factors appear to affect cognitive processing (as indexed by P300) differentially in men and women.


Acid-Catalyzed Synthesis of Isatoic Anhydride-8-Secondary Amides Enables IASA Transformations for Medicinal Chemistry.
Quinazolin-dione-N-3-alklyl derivatives are the core scaffolds for several categories of bioactive small molecules, but current synthetic methods are costly, involve environmental hazards, and are not uniformly scalable. Here, we report an inexpensive, flexible, and scalable method for the one-pot synthesis of substituted quinazolin-dione-N-3-alkyls (isomers of isatoic-8-secondary amides (IASAs)) from isatin that take advantage of in situ capture of imidic acid under acidic conditions. We further show that this method can be used for the synthesis of a wide variety of derivatives with medicinal uses.


Cardiac function and tolerance to ischemia/reperfusion injury in a rat model of polycystic ovary syndrome during the postmenopausal period.
There is much controversy regarding whether cardiovascular events increase in women with polycystic ovary syndrome (PCOS) with aging. Considering the lack of possibility of certain investigations in humans, animal models of PCOS may be suitable resources to obtain the useful data needed. In this study; we aimed to investigate whether cardiac function and tolerance to ischemia/reperfusion (I/R) injury worsen in postmenopausal rats, who had PCOS at younger ages, compared to controls. The hearts of aged rats with a history of PCOS and their controls were isolated and perfused in a Langendorff apparatus. Values of hemodynamic parameters, including left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), rate pressure product (RPP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) were recorded using a power lab system. Blood serum levels of total testosterone (TT) and estradiol (E2) were determined by ELISA kits. Generalized Estimating Equation Model and t-student unpaired test results were used to compare the findings documented between two groups. No statistically significant differences were observed in hemodynamic parameters of the heart including, LVSP, LVDP, RPP and ±dp/dt, between the rats of two groups of study, at baseline or before ischemia and after I/R. Nor were any significant differences observed in the levels of two hormones between the two groups (p > 0.05). History of PCOS during reproductive ages should not be considered an important risk factor for reduction in cardiac contractile function or less tolerance to I/R injury during the postmenopausal period.


Bone graft fixation in anterior cruciate ligament reconstruction evaluated by radiostereometric analysis.
For most anterior cruciate ligament reconstruction techniques, the tensile strength of the ligament substitutes and the surgical methods of fixation have been examined. In the present study seven consecutive patients with a chronic anterior cruciate ligament deficiency, who were reconstructed with a bone-patellar tendon-bone graft, were followed. The migration of the bone blocks was examined with radiostereometric analysis immediately postoperatively and after 3 and 12 months. The median migration of the bone blocks in the femur was 0.4 mm and in the tibia 0.4 mm. Clinical examination was undertaken preoperatively and one year postoperatively. We conclude that the use of interference screws seems to be a reliable method for fixation in anterior cruciate reconstruction and that healing of the bone blocks occurs during the first three postoperative months.


Blocking TNF-α enhances Pseudomonas aeruginosa-induced mortality in burn mice through induction of IL-1β.
Tumor necrosis factor (TNFα) is a proinflammatory cytokine and has been a target for intervention in human sepsis. However, inhibition of TNF-α with a high dose of a TNF-receptor fusion protein in patients with septic shock worsened patient survival. This study was designed to investigate whether blocking TNF-α enhances mortality in infected burn mice through the induction of IL-1β. WT or Tnfrsf1a(-/-) mice received Pseudomonas aeruginosa injection in the back at 8h after burn injury. The animals were sacrificed at 24h after burn and lung tissues were harvested and examined for determining myeloperoxidase (MPO) activity, pulmonary microvascular dysfunction, NF-κB DNA binding activity, and IL-1β expression. Also, the lung and blood were harvested for bacterial count assay. Thermal injury alone induced NF-κB DNA binding activity and neutrophil infiltration in the lung in WT but not in Tnfrsf1a(-/-) mice. A 50% total body surface area (TBSA) burn induced a significant increase of mortality in WT compared with Tnfrsf1a(-/-) mice. In contrast, P. aeruginosa injection with a 30% TBSA burn pretreatment enhanced IL-1β expression, bacterial counts in lung and blood, pulmonary microvascular dysfunction, and mortality in Tnfrsf1a(-/-) mice compared with WT mice. Injection of the IL-1 receptor antagonist, Anakinra, reduced P. aeruginosa infection with burn pretreatment-induced blood bacterial counts, IL-1β levels as well as permeability of lung, and mortality in Tnfrsf1a(-/-) mice. Our findings suggest that thermal injury induces lung NF-κB activation and neutrophil sequestration through TNFα signaling. However, blocking TNF-α enhances P. aeruginosa infection-induced lung damage in burn mice via induction of IL-1β. Using an IL-1 receptor antagonist combined with the neutralization of TNF-α could be a useful strategy for decreasing P. aeruginosa infection-induced mortality in burn patients.


Turning waste expanded polystyrene into lightweight aggregate: Towards sustainable construction industry.
With the limited supply of energies that we can extract or mine from the earth, low energy consumption building is indeed a demand for the present situation with the use of sustainable building materials. Owing to the frequent use of EPS in the packaging industry, the versatile use of non-biodegradable EPS contributes to increasing global waste generation. In this regard, the utilization of recycled EPS in concrete production can be a sustainable approach to manage embodied energy. EPS is a very lightweight thermal insulating material and is primarily used to prepare lightweight concrete and thermal insulation products in the construction sector. Currently, EPS-based cementitious composites are used in many building structures due to their excellent durability, thermal performance, and sustainability benefits. Several extensive studies have been carried out over a few years to maximize the hardened and durability properties of EPS concrete. With a number of building materials emerging, there is a lack of in-depth review studies on the performance of EPS aggregate concrete. The study underlines the influence of the addition of EPS to lightweight concrete in terms of mechanical, durability, and thermal insulation properties. The main contribution of this article lies in the exploration of subsequent additives, for the production of modified EPS to improve the performance of concrete. Further, the review is expected to provide substantial knowledge on the potential use of EPS, to promote sustainability in the construction sector.


A multicenter study of genetic testing for Parkinson's disease in the clinical setting.
Parkinson's disease (PD) guidelines lack clear criteria for genetic evaluation. We assessed the yield and rationale of genetic testing for PD in a routine clinical setting on a multicenter cohort of 149 early-onset and familial patients by exome sequencing and semi-quantitative multiplex ligation-dependent probe amplification of evidence-based PD-associated gene panel. We show that genetic testing for PD should be considered for both early-onset and familial patients alike, and a clinical yield of about 10% in the Caucasian population can be expected.


Cacogeusia following pine nut ingestion: a six patient case series.
This is a retrospective case series of 6 patients complaining of a bad taste (cacogeusia) specifically metallogeusia, following the ingestion of pine nuts.(1) The taste arose always within 48h of ingestion, and in all but one patient spontaneously resolved within 14 days. Pine nuts also have a potential for triggering anaphylaxis.(2).


Prospective, Multicenter, Cross-Sectional Survey on Dry Eye Disease in Japan.
Dry eye disease (DED) is commonly encountered in eye clinics and hospitals, and it is therefore very important to understand DED prevalence in outpatients. A multicenter, hospital-based cross-sectional study was conducted among outpatients in Japan to ascertain DED prevalence and relationships between DED and patient profiles, including eye disease, DED diagnosis history, and surgical history. DED was diagnosed according to diagnostic criteria of the Asia Dry Eye Society. Patient self-assessment of DED-related subjective symptoms was conducted using the 5-Item Dry Eye Questionnaire (DEQ-5). Tear break-up time was evaluated in subjective symptom-positive patients. The prevalence of DED was 55.7% in 990 patients (mean age 69.1 ± 13.4 years), DED was commonly experienced in combination with other ocular diseases. In revisiting patients, 15.2% had not previously been diagnosed as DED, and their total DEQ-5 scores were higher than those of patients who had undergone DED treatment. This study revealed that more than half of the outpatients had DED. Among revisiting patients, there were many "hidden" DED patients who had not been diagnosed with DED in the past. There is a high likelihood of finding DED comorbidity in patients with other eye diseases in eye clinics and hospitals. Santen Pharmaceutical Co., Ltd. UMIN Clinical Trials Registry Identifier, UMIN000035506.


Antesternal pharyngogastrostomy by oral insertion of a stapler.
Cancer of the hypopharynx and cervical esophagus involve problems such as removal of the cervical region, resection of the esophagus and also esophageal reconstruction. A standard surgical procedure has not been established. In our clinic, surgery is performed by two teams; one for head and neck and the other for the digestive tract. Since 1963, we have performed 22 operations on patients with such cancers; resection of the cancer and reconstruction of the alimentary tract were performed in sixteen 16 patients and palliative operations in six. As procedures of reconstructive surgery, antesternal pharyngogastrostomy was performed in ten patients, and antesternal esophagogastrostomy in one. Six of these reconstructions were carried out with oral insertion of a stapler. In this paper, we present the surgical techniques and some of the problems involved in total esophagectomy without thoracotomy, i.e., blunt dissection of the esophagus and antesternal pharyngogastrostomy, particularly pharyngogastrostomy, using a stapler inserted orally.


A comparison of the efficacy of sublingual and oral misoprostol 400 microgram in the management of early pregnancy failure: a randomized controlled trial.
To compare repeated doses of sublingual with oral misoprostol in the medical management of early pregnancy failure. One hundred and thirty eight women with a period of gestation less than 20 week calculated by her last menstrual period and less than 12 weeks by size were sequentially allocated to two groups to receive either 400 microg of misoprostol orally or sublingually every 4 hours until termination of pregnancy was completed. There is no difference in the mean induction to abortion interval. Fever and chill were more common in sublingual group compared with oral group. The other adverse effects were similar and included nausea, vomiting, diarrhea, abdominal pain, and headache. Sublingual misoprostol is as effective as oral route. Most adverse effects are similar in both groups except fever was more common in sublingual group.


Role of prostaglandin E (PGE) in the modulation of the action of vasopressin on water flow in the urinary bladder of the toad and mammalian kidney.
PGE1 and PGE2 are known to interfere with the water permeability effect of vasopressin in toad bladder and kidney. It has been proposed that endogenous prostaglandin E (PGE), synthesized within cells of vasopressin-sensitive tissues, serves to modulate the permeability changes elicited by the neurohypophyseal hormone. Direct evidence in support of this hypothesis is as follows: vasopressin increases the biosynthesis of PGE2 in renal interstitial cells and in isolated toad bladder. In the latter, inhibition of vasopressin-induced synthesis of PGE by a variety of inhibitors results in a greater water permeability response to vasopressin. It appears that vasopressin has two effects in toad bladder and kidney: (i) it activates adenylate cyclase thereby increasing the concentration of adenosine 3',5' monophosphate (cyclic AMP), the nucleotide responsible for the resultant increase in water permeability; and (ii) it activates a phospholipase that serves to release arachidonic acid, the precursor of PGE2 from intracellular pools. The PGE derived from the arachidonic acid diminishes adenylate-cyclase activity, in consequence of which the response of the enzyme to vasopressin is modulated.


Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21.
The Helicobacter pylori CagA bacterial oncoprotein plays a critical role in gastric carcinogenesis. Upon delivery into epithelial cells, CagA causes loss of polarity and activates aberrant Erk signaling. We show that CagA-induced Erk activation results in senescence and mitogenesis in nonpolarized and polarized epithelial cells, respectively. In nonpolarized epithelial cells, Erk activation results in oncogenic stress, up-regulation of the p21(Waf1/Cip1) cyclin-dependent kinase inhibitor, and induction of senescence. In polarized epithelial cells, CagA-driven Erk signals prevent p21(Waf1/Cip1) expression by activating a guanine nucleotide exchange factor-H1-RhoA-RhoA-associated kinase-c-Myc pathway. The microRNAs miR-17 and miR-20a, induced by c-Myc, are needed to suppress p21(Waf1/Cip1) expression. CagA also drives an epithelial-mesenchymal transition in polarized epithelial cells. These findings suggest that CagA exploits a polarity-signaling pathway to induce oncogenesis.


Telomeric Region of the Spinal Muscular Atrophy Locus Is Susceptible to Structural Variations.
Most patients with spinal muscular atrophy lack the survival motor neuron 1 gene (SMN1) in the telomeric region of the spinal muscular atrophy locus on chromosome 5q13. On the other hand, the copy number of SMN2, a centromeric homolog of SMN1, is increased in many of these patients. This study aimed to clarify the mechanism underlying these structural variations. We determined the copy numbers of telomeric and centromeric genes in the spinal muscular atrophy locus of 86 patients and 22 control subjects using multiplex ligation-dependent probe amplification analysis. Then, we chose 74 patients lacking SMN1 exons 7 and 8, and compared their dataset with that of 22 control subjects retaining SMN1 exons 7 and 8. The SMN2 copy number was shown to vary widely and to correlate with the disease severity of the patients. Interestingly, telomeric NAIP and telomeric GTF2H2 showed similar tendencies. We also noted positive correlations among the copy number of SMN2 and the telomeric genes of the spinal muscular atrophy locus. However, the copy numbers of centromeric NAIP and centromeric GTF2H2 were stable among the patients, with both approximating a value of two. Our findings suggested that the telomeric region of the spinal muscular atrophy locus appears to be susceptible to structural variation, whereas the centromeric region is stable. Moreover, according to our results, new SMN2 copies may be generated in the telomeric region of the spinal muscular atrophy locus, supporting the SMN1-to-SMN2 gene conversion theory.


Telomerase ribonucleoprotein and genome integrity-An emerging connection in protozoan parasites.
Telomerase has an established role in telomere maintenance in eukaryotes. However, recent studies have begun to implicate telomerase in cellular roles beyond telomere maintenance. Specifically, evidence is emerging of cross-talks between telomerase mediated telomere homeostasis and DNA repair pathways. Telomere shortening due to the end replication problem is a constant threat to genome integrity in eukaryotic cells. This poses a particular problem in unicellular parasitic protists because their major virulence genes are located at the subtelomeric loci. Although telomerase is the major regulator of telomere lengthening in eukaryotes, it is less studied in the ancient eukaryotes, including clinically important human pathogens. Recent research is highlighting interplay between telomerase and the DNA damage response in human parasites. The importance of this interplay in pathogen virulence is only beginning to be illuminated, including the potential to highlight novel developmental regulation of telomerase in parasites who transition between multiple developmental stages throughout their life cycle. In this review, we will discuss the telomerase ribonucleoprotein enzyme and DNA repair pathways with emerging views in human parasites to give a broader perspective of the possible connection of telomere, telomerase, and DNA repair pathways across eukaryotic lineages and highlight their potential role in pathogen virulence. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.


Low-dose warfarin versus external pneumatic compression for prophylaxis against venous thromboembolism following total hip replacement.
Lower doses of warfarin are effective in the treatment of proven proximal deep vein thrombosis (DVT), and at a substantially lower risk of bleeding complications than with standard doses. The authors compared low-dose warfarin with external pneumatic compression (EPC) boots for prophylaxis against DVT and efficacy and safety in a population of total hip replacement patients at high risk for DVT and bleeding complications. DVT developed in 12 of 72 patients on low-dose warfarin and 11 of 66 patients on EPC. Both regimens were as efficacious as traditional higher doses of warfarin used in prior studies. No major bleeding complications occurred in either group. Low-dose warfarin appears to be an effective and relatively safe form of prophylaxis against postoperative DVT, as does sequential EPC of the calf and thigh.


Universally applicable methods for monitoring response regulator aspartate phosphorylation both in vitro and in vivo using Phos-tag-based reagents.
Recent development of the phosphate chelator, Phos-tag, together with Phos-tag pendant reagents, has provided new methods for detection of phosphorylated serine, threonine, tyrosine, and histidine residues in phosphoproteins. We have investigated the use of Phos-tag for detection and quantification of phospho-aspartate in response regulator proteins that function within two-component signaling systems. Alternative methods are especially important, because the labile nature of the acylphosphate bond in response regulator proteins has restricted the application of many traditional methods of phosphoprotein analysis. We demonstrate that Phos-tag gel stain can be used to detect phospho-Asp in response regulators and that Phos-tag acrylamide gel electrophoresis can be used to separate phosphorylated and unphosphorylated forms of response regulator proteins. The latter method, coupled to Western blot analysis, enables detection of specific phosphorylated proteins in complex mixtures such as cell lysates. Standards of phosphorylated proteins can be used to correct for hydrolysis of the labile phospho-Asp bond that invariably occurs during analysis. We have employed Phos-tag methods to characterize the phosphorylation state of the Escherichia coli response regulator PhoB both in vitro, using purified protein, and in vivo, by analyzing lysates of cells grown under different conditions of induction of the PhoR/PhoB phosphate assimilation pathway.


Native extracellular matrix preserves mesenchymal stem cell "stemness" and differentiation potential under serum-free culture conditions.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) for clinical use should not be grown in media containing fetal bovine serum (FBS), because of serum-related concerns over biosafety and batch-to-batch variability. Previously, we described the preparation and use of a cell-free native extracellular matrix (ECM) made by bone marrow cells (BM-ECM) which preserves stem cell properties and enhances proliferation. Here, we compare colony-forming ability and differentiation of MSCs cultured on BM-ECM with a commercially available matrix (CELLstart™) and tissue culture plastic (TCP) under serum-free conditions. Primary MSCs from freshly isolated bone marrow-derived mononuclear cells or passaged MSCs (P1) were grown in serum-containing (SCM) or serum-free (SFM) media on BM-ECM, CELLstart™, or TCP substrates. Proliferation, cell composition (phenotype), colony-forming unit replication, and bone morphogenetic protein-2 (BMP-2) responsiveness were compared among cells maintained on the three substrates. Proliferation of primary BM-MSCs was significantly higher in SCM than SFM, irrespectively of culture substrate, suggesting that the expansion of these cells requires SCM. In contrast, passaged cells cultured on BM-ECM or CELLstart™ in SFM proliferated to nearly the same extent as cells in SCM. However, morphologically, those on BM-ECM were smaller and more aligned, slender, and long. Cells grown for 7 days on BM-ECM in SFM were 20-40 % more positive for MSC surface markers than cells cultured on CELLstart™. Cells cultured on TCP contained the smallest number of cells positive for MSC markers. MSC colony-forming ability in SFM, as measured by CFU-fibroblasts, was increased 10-, 9-, and 2-fold when P1 cells were cultured on BM-ECM, CELLstart™, and TCP, respectively. Significantly, CFU-adipocyte and -osteoblast replication of cells grown on BM-ECM was dramatically increased over those on CELLstart™ (2X) and TCP (4-7X). BM-MSCs, cultured in SFM and treated with BMP-2, retained their differentiation capacity better on BM-ECM than on either of the other two substrates. Our findings indicate that BM-ECM provides a unique microenvironment that supports the colony-forming ability of MSCs in SFM and preserves their stem cell properties. The establishment of a robust culture system, combining native tissue-specific ECM and SFM, provides an avenue for preparing significant numbers of potent MSCs for cell-based therapies in patients.


Childhood cancers: Analysis of 1279 cases at Armed Forces Institute of Pathology, Rawalpindi, Pakistan.
To determine the clinicopathological pattern of childhood malignancies registered with a pathology-based tumour registry. The descriptive retrospective study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised data related to all the histologically diagnosed malignant childhood tumours in the institutional tumour registry from January 2009 to December 2018. Data was analysed using SPSS 20 for the site of involvement, age distribution and histological types of tumours. Of the total 37793 malignant tumours, 1279(3.38%) were in paediatric subjects aged <15 years. There were 820(64.1%) male subjects and 459(35.8%) were female. Lymph node malignancies were the commonest 261(20.4%), followed by eye tumours 251(19.6%), and brain 107(8.3%). Lymphomas and eye tumours were found to form the main bulk of childhood cancer.


Norepinephrine stimulates amylase release from pancreatic acini.
alpha-Adrenergic blockade decreases food-stimulated amylase secretion in dogs, suggesting that physiologic sympathetic nerve discharge of norepinephrine enhances pancreatic enzyme secretion. Previous studies have not separated direct effects of adrenergic agonists on pancreatic exocrine cells from effects on blood flow. An in vitro preparation of dispersed acini from guinea pig pancreas was modified and amylase release in response to common pancreatic stimulants was measured. It was demonstrated that physiologic concentrations of norepinephrine enhance amylase release from dispersed pancreatic acini evoked by supramaximal concentrations of cholecystokinin. These observations suggest that the sympathetic nervous system plays a role in modulating pancreatic enzyme secretion independent of effects on blood flow.


Diabetes Alert Dogs (DADs): An assessment of accuracy and implications.
To test the accuracy of Diabetes Alert Dogs (DADs) by comparing recorded alerts to continuous glucose monitoring (CGM) device readings during waking and sleeping hours. 14 individuals (7 adults with type 1 diabetes and 7 youth with type 1 diabetes/parents) who owned DADs for ≥6 mos wore masked CGM devices over a several-week period while recording DAD alerts electronically and in paper diaries. During waking hours, sensitivity scores across participants were 35.9% for low BG events and 26.2% for high BG events. DAD accuracy was highly variable with 3/14 individual dogs performing statistically higher than chance. Sensitivity scores were lower during sleep hours of the person with diabetes (22.2% for low BG events and 8.4% for high BG events). DAD accuracy during sleeping hours was also highly variable, with 1/11 individual dogs performing statistically better than chance. Rate of change analyses indicated that DADs were responding to absolute BG level, rather than rapid shifts in glucose levels. In this study the majority of DADs did not demonstrate accurate detection of low and high BG events. However, performance varied greatly across DADs and additional studies are needed to examine factors contributing to this variability. Additionally, more research is needed to investigate the significant gap between the positive experiences and clinical outcomes reported by DAD owners and the mixed research findings on DAD accuracy.


Development of the amino acid pools in chick embryo brain, heart, and eye: taurine, valine, glutamine, and phosphoethanolamine.
The redistribution of valine, from the nonrenewable yolk supply into excitable tissues, was studied during the first 15 days of chick embryogenesis. Valine levels in the extraembryonic circulation (the vitelline plexus) peak between days 7-9 (E7-9) and then decline steeply. In their first phase of differentiation (E2-E4), all embryonic tissues contain more valine than the blood plexus. From E4 to E7, the heart and brain exhibit initially a rapid fall in valine, but from day 7 on the decrease becomes more gradual. The eye during the same period reaches an equilibrium with circulating valine; as these levels fall from E9 to E15, the eye retains the valine that accumulated. Against this pattern of change, characteristic for an essential amino acid during embryogenesis, glutamine levels are at any time from two- to threefold higher than valine in all tissues. In the circulation, this ratio remains constant throughout the 15 days of embryonic development. Eye glutamine, higher on day 4, by E7 has entered into an equilibrium with glutamine in the plexus. A steady but two times higher glutamine level is maintained in the heart, although during the later stages of development it gradually tends to approach the plexus content. In sharp contrast, starting on E7 and accelerating on E9, a large increase of glutamine relative to valine or other essential amino acids is seen in developing brain tissue. This appears typical for most metabolic amino acids, suggesting that by days 9-10 the essential amino acid supply in the brain is being exhausted.(ABSTRACT TRUNCATED AT 250 WORDS)


Radioprotective effect of montelukast sodium in rat lacrimal glands after radioiodine treatment.
The aim of this study was to evaluate the morphological changes of rat lacrimal glands at the third month following radioiodine (RAI) treatment and the radioprotective effect of montelukast (ML) sodium against RAI-related lacrimal gland damage. Fifty female Wistar Albino rats were divided into three groups. The control group (n=10) consisted of rats with no intervention. RAI group (n=20) consisted of rats treated with oral (131)I (111 MBq). The ML group (n=20) consisted of rats treated with intraperitoneal 10mg/kg/day ML sodium, starting three days before and continuing for one week after oral RAI administration. Intraorbital (IG), extraorbital (EG) and Harderian glands (HG) were removed bilaterally after three months. The existence of acinar atrophy, acinar fibrosis, abnormal cell lines, peripheral basophilia, cell size variation and decrease in amount of cytoplasm was significantly more common in the RAI-rat treated group than in the ML group, in each of the glands. The ML-treated group had less-frequent cell shape variation in EG (P=0.001) and HG (P=0.027), cell size variation in IG (P<0.001) and HG (P=0.01), ductal pathology in EG (P<0.001) and HG (P<0.001) and lipofuscin accumulation in EG (P=0.001) and in HG (P=0.01) than the RAI-treated group. RAI treatment seems to cause morphological damage to rat lacrimal glands, and ML sodium effectively protects against damage to lacrimal glands.


In silico analysis of prion protein mutants: a comparative study by molecular dynamics approach.
Polymorphisms in the human prion proteins lead to amino acid substitutions by the conversion of PrPC to PrPSc and amyloid formation, resulting in prion diseases such as familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia. Cation-π interaction is a non-covalent binding force that plays a significant role in protein stability. Here, we employ a novel approach by combining various in silico tools along with molecular dynamics simulation to provide structural and functional insight into the effect of mutation on the stability and activity of mutant prion proteins. We have investigated impressions of prevalent mutations including 1E1S, 1E1P, 1E1U, 1E1P, 1FKC and 2K1D on the human prion proteins and compared them with wild type. Structural analyses of the models were performed with the aid of molecular dynamics simulation methods. According to our results, frequently occurred mutations were observed in conserved sequences of human prion proteins and the most fluctuation values appear in the 2K1D mutant model at around helix 4 with residues ranging from 190 to 194. Our observations in this study could help to further understand the structural stability of prion proteins.


Impact of exacerbations of cystic fibrosis on muscle strength.
Adult patients with cystic fibrosis have peripheral muscle weakness, which is related to exercise intolerance and poor prognosis. The influence of acute exacerbations on muscle strength has been poorly studied. This study aimed to investigate whether quadriceps force (QF), as assessed with an involuntary technique, changes during intravenous antibiotics therapy (IVAT) for an exacerbation. QF was measured in 20 patients using twitch stimulation of the femoral nerve at the day of hospitalization (day 1) and at termination (day 14) of the IVAT. Physical activity was monitored during IVAT using a SenseWear armband. Ten stable patients served as control subjects. QF did not change during exacerbation (potentiated twitch force at day 1: 140 ± 42 N, at day 14: 140 ± 47 N), but a decrease was observed in individual patients. Changes in twitch force during exacerbation were correlated with time spent in activities of at least moderate intensity (r = 0.61, p = 0.007). QF does not systematically decrease during exacerbations of cystic fibrosis. Individual changes in QF are well correlated with daily time spent in activities of at least moderate intensity.


Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples.
Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue.


New neolignans from Talauma ovata.
The hexane extract of the bark of Talauma ovata yielded three new natural neolignans, identified as acetyl oleiferin-C (4), acetyl oleiferin-F (7) and acetyl oleiferin-G (8), together with the known compounds dihydroguaiaretic acid (1), austrobailignan-5 (2), oleiferin-C (3), austrobailignan-6 (5) and oleiferin-F (6).


Primary mucoepidermoid carcinoma of the thyroid: diagnosis by fine-needle aspiration biopsy.
Fine-needle aspiration biopsy (FNAB) has been recognized as a safe and reliable procedure in the evaluation of thyroid nodules. We herein report a case of a low-grade mucoepidermoid carcinoma of the thyroid that was diagnosed with this technique. Examination of an intra-operative FNAB showed cohesive clusters of polygonal squamoid cells with distinct cellular borders, uniform round nuclei, distinct nucleoli, and homogeneous amphophilic to cyanophilic cytoplasm. Focal keratin "pearl" formation was apparent, along with extracellular, lightly basophilic mucin deposits mantled by squamoid cells. These cytologic features are characteristic of low-grade mucoepidermoid carcinoma, as seen in other anatomic sites. This impression was confirmed by examination of paraffin sections. Previous reports have indicated that mucoepidermoid thyroid carcinoma is an indolent, locally recurring lesion. However, in spite of low-grade histology in our case, the neoplasm presented with distant metastases to bones, pleura, and lung.


Experimental investigation and molecular dynamics simulation of the binding of ellagic acid to bovine liver catalase: Activation study and interaction mechanism.
Ellagic acid (ELA), as a polyphenolic natural compound and food additive, which has reported to possess anti-carcinogenic, antioxidant, antidepressant, ameliorative and anti-mutagenic effects. In the current work, the effects of ELA on the conformation and catalytic activity of catalase were investigated by using spectroscopic techniques including ultraviolet visible (UV-vis), fluorescence, synchronous fluorescence and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy as well as molecular dynamics (MD) simulation. Kinetic studies showed that the enzymatic activity of catalase increases in the presence of ELA (almost 2-fold higher than free enzyme activity). Moreover, analysis of fluorescence data revealed two binding sites for ELA on the catalase and static type of quenching mechanism. The binding constants between ELA and catalase were obtained to be 47.35 × 107 M-1 (at 298 K) and 17.60 × 107 M-1 (at 310 K) and the binding distance was calculated to be 2.83 nm. Thermodynamic data showed that hydrogen bonds have a main role in the ELA-catalase complex formation. The best binding sites for ELA were, in the middle of β-barrel and wrapping domain and in the middle of β-barrel and helical domain, according to molecular docking data. MD simulation results were confirmed that ELA can increase catalase activity through increasing the distance between an upper side α-helix structure and a down side random coil structure.


Computation of dynamical correlation functions of heisenberg chains in a magnetic field.
We compute the momentum- and frequency-dependent longitudinal spin structure factor for the spin-1/2 XXZ Heisenberg spin chain in a magnetic field, using exact determinant representations for form factors on the lattice. Multiparticle (i.e., multispinon) contributions are computed numerically throughout the Brillouin zone, yielding saturation of the sum rule to high precision.


Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits.
Terbinafine hydrochloride (T-HCl) is recommended for the management of fungal keratitis. To maintain effective aqueous humor concentrations, frequent instillation of T-HCl drops is necessary. This work aimed to develop alternative controlled-release in situ ocular drug-loaded nanoemulsion (NE) gels. Twelve pseudoternary-phase diagrams were constructed using oils (isopropyl myristate/Miglyol 812), surfactants (Tween 80/Cremophor EL), a co-surfactant (polyethylene glycol 400) and water. Eight drug-loaded (0.5%, w/v) NEs were evaluated for thermodynamic stability, morphology, droplet size and drug release in simulated tear fluid (pH 7.4). Following dispersion in gellan gum solution (0.2%, w/w), the in situ NE gels were characterized for transparency, rheological behavior, mucoadhesive force, drug release and histopathological assessment of ocular irritation. Drug pharmacokinetics of sterilized F31 [Miglyol 812, Cremophor EL: polyethylene glycol 400 (1:2) and water (5, 55 and 40%, w/w, respectively)] in situ NE gel and oily drug solution were evaluated in rabbit aqueous humor. The NEs were thermodynamically stable and have spherical droplets (<30 nm). The gels were transparent, pseudoplastic, mucoadhesive and showed more retarded zero-order drug release rates. F31 in situ NE gel showed the least ocular irritation potential and significantly (P<0.01) higher C(max), delayed T(max), prolonged mean residence time and increased bioavailability.


Coronavirus mRNA synthesis involves fusion of non-contiguous sequences.
Positive-stranded genomic RNA of coronavirus MHV and its six subgenomic mRNAs are synthesized in the cytoplasm of the host cell. The mRNAs are composed of leader and body sequences which are non-contiguous on the genome and are fused together in the cytoplasm by a mechanism which appears to involve an unusual and specific 'polymerase jumping' event.


Detection of Alphacoronavirus in velvety free-tailed bats (Molossus molossus) and Brazilian free-tailed bats (Tadarida brasiliensis) from urban area of Southern Brazil.
A survey was carried out in search for bat coronaviruses in an urban maternity roost of about 500 specimens of two species of insectivorous bats, Molossus molossus and Tadarida brasiliensis, in Southern Brazil. Twenty-nine out of 150 pooled fecal samples tested positive by reverse transcription-PCR contained fragments of the RNA-dependent RNA polymerase gene of coronavirus-related viruses. The sequences clustered along with bat alphacoronaviruses, forming a subcluster within this group. Our findings point to the need for risk assessment and continued surveillance of coronavirus infections of bats in Brazil.