Effect of surgery resident change of shift on trauma resuscitations and outcomes.
The ability of surgery residents to provide continuity of care has come under scrutiny with work hour restrictions. The impact of the surgery resident sign-out period (6-8am and 6-8pm) on trauma outcomes remains unknown. We hypothesize that during shift change, resuscitation times are prolonged with worse outcomes. Records of patients treated at a university-based urban trauma center during 2008 and 2009 were reviewed. Patients were separated into a shift change group (6-8am and 6-8pm) and a control group of all other time periods and compared using ANOVA, chi square, and unpaired t-tests. We reviewed the charts of 4361 consecutive trauma patients. There was no difference in gender, acuity, resuscitation times, Glasgow Coma Scale, revised trauma score, injury severity score (ISS), or probability of survival score between patients arriving during shift change compared to other times (p>0.2). There was no difference in total emergency department time for patients arriving during shift change (p = 0.07), even when stratified by ISS (ISS<15, p = 0.09; ISS>15, p = 0.2). Length of stay was increased for patients arriving during shift change compared to other times (5 vs 4 days, p<0.05). This was more pronounced for those with ISS>15 (16 vs 11 days, p = 0.03); however, there was no impact on intensive care unit length of stay, ventilator days, and mortality (p>0.3) regardless of ISS. Trauma outcomes are generally unaffected by patient arrival during shift change when resident sign-outs occur. Although adaptations are being made to accommodate trauma patient arrival during these times, we need to continue paying close attention, especially to seriously injured patients, to ensure that there are no delays in care that may potentially affect patient outcomes.


Modulations of urinary lipid mediators in acute bladder cystitis.
Bioactive lipids, such as lysophospholipids, ceramides, and eicosanoids and related mediators, have been demonstrated to be involved in inflammation. We aimed to investigate the possible orchestral modulations of these bioactive lipids in human inflammation. We simultaneously measured the urinary levels of lysophospholipids, ceramides, and eicosanoids and related mediators by a liquid chromatography-mass spectrometry method in patients with cystitis and control subjects. The urinary levels of lysophosphatidylcholine, lysophosphatidylethanolamine, sphingosine 1-phosphate, ceramides, prostaglandin (PG)E2 and its metabolites represented by tetranor-PGEM, several oxylipins, DHA, and lysoPAF were higher in patients with cystitis. Urinary levels of some species of glycerolysophospholipids were highly positively correlated with those of other species of the same glycerolysophospholipids. Cluster analyses revealed that lysophosphatidylcholine was close to a PGE2 metabolite, lysophosphatidylethanolamine was close to DHA, and sphingosine 1-phosphate and ceramides were close to lysoPAF. The orchestral dynamism of the lipid mediators was observed in the urine of cystitis, suggesting the necessity for simultaneous investigation of lipid mediators for translational research.


[Pulmonary fibrosis after postoperative tangential irradiation in breast cancer].
Incidence rate of pulmonary fibrosis with elevation of diaphragma was calculated for 118 postoperated breast cancer patients who were tangentially irradiated at the Department of Radiology Kyushu University from 1961 to 1980 and followed more than 5 years. 5%, 50% occurred at 40-45 Gy, 60-65 Gy, Rubin's Table (1972) is possible correct.


Classification of illicit heroin by UPLC-Q-TOF analysis of acidic and neutral manufacturing impurities.
The illicit manufacture of heroin results in the formation of trace levels of acidic and neutral manufacturing impurities that provide valuable information about the manufacturing process used. In this work, a new ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) method; that features high resolution, mass accuracy and sensitivity for profiling neutral and acidic heroin manufacturing impurities was developed. After the UPLC-Q-TOF analysis, the retention times and m/z data pairs of acidic and neutral manufacturing impurities were detected, and 19 peaks were found to be evidently different between heroin samples from "Golden Triangle" and "Golden Crescent". Based on the data set of these 19 impurities in 150 authentic heroin samples, classification of heroin geographic origins was successfully achieved utilizing partial least squares discriminant analysis (PLS-DA). By analyzing another data set of 267 authentic heroin samples, the developed discrimiant model was validated and proved to be accurate and reliable.


The potential role of HIF on tumour progression and dissemination.
Cancer is the second cause of mortality worldwide, primarily owing to failure to cure metastatic disease. The need to target the metastatic process to reduce mortality is clear and research over the past decade has shown hypoxia-inducible factor-1 (HIF-1) to be one of the promising targets. In order for metastatic disease to be established, multiple steps need to be taken whereby the tumour cells escape into the bloodstream and survive, disseminate and then establish at a premetastatic niche. HIF-1 mediates hypoxia-induced proangiogenic factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which promote extravasation and chemotaxis. The migration of tumour cells is mediated by loss of E-cadherin, which results in a more invasive phenotype; dissemination of the tumour cells by increased vascular permeability and survival in the bloodstream through resistance to apoptosis as well as adhesion at the premetastatic niche are all controlled by factors under the influence of HIF-1. The overexpression of HIF in many aggressive cancer types as well as its role in the establishment of metastatic disease and treatment resistance demonstrate its potential target in therapeutics. Taken together, the role of HIF-1 in cancer and metastatic disease is clear and the need for better treatment targeting metastases is paramount; more aggressive phenotypes with less response to treatment are associated with HIF-1 expression. Our research has shown promise but many questions still remain to be answered.


Exploring usability characteristics in computer-based digital health technologies for family caregivers of people with chronic progressive conditions: a scoping review protocol.
The objective of this scoping review is to map the literature on how usability is considered during the design and/or evaluation of computer-based digital health technologies for family caregivers of persons with chronic progressive conditions. Computer-based digital health technologies offer convenient alternatives for delivering interventions to caregivers of people with chronic progressive conditions. Usability is a critical component of good practice in developing and implementing health and social care technologies; however, we need to determine whether usability is incorporated in the design and/or evaluation of computer-based digital health technologies for caregivers of people with chronic progressive conditions. Within this context, a broad overview of the existing literature on usability in computer-based digital health technologies is needed. We will include studies published from 2012 to the present that describe usability characteristics of computer-based digital health technologies targeting adult (≥18 years old) family caregivers of people with chronic progressive conditions, regardless of study design or setting. We will use the JBI methodology for scoping reviews. We will conduct searches of MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), and Web of Science Core Collection to capture eligible studies. After the results are deduplicated, 2 independent reviewers will assess each study for eligibility and extract data from the included studies. Conflicts will be resolved through discussion or with a third reviewer. Data analysis will use a textual narrative synthesis approach. Open Science Framework osf.io/w4vk5.


Ubiquinone in Rhodopseudomonas sphaeroides. Some thermodynamic properties.
In Rhodopseudomonas sphaeroides chromatophores there are 25 +/- 3 ubiquinone (Q) molecules/reaction center protein. They comprise several thermodynamically and functionally different ubiquinone complements. There are approx. 19 ubiquinones (Em7 = 90 mV) in the main ubiquinone complement which, within experimental resolution, appears thermodynamically homogenous and follows the redox reaction Q + 2e + 2H+ in equilibrium with QH2 from pH 5--9. A method which takes advantage of the 2H+ bound/molecule of Q reduced is described for measuring the time course of light-activated reaction center-driven reduction and oxidation of the 19 Q complement. No stable semiquinones were detected in the constitutents of the 19 Q complement. There are approx. 6 ubiquinones of lower Em which are currently unaccounted for, although one or possibly two of these can be assigned to the quinones of the reaction center protein. The remainder may be associated with the NADH-ubiquinone oxidoreductase.


Dinucleotide repeat polymorphisms in the neprilysin gene are not associated with sporadic Alzheimer's disease.
In the pathological process of Alzheimer's disease (AD), deposition of amyloid beta-peptide (A beta) in the brain parenchyma plays an important role. Neprilysin (NEP), a neutral endopeptidase, degrades A beta, and it is postulated that decreased NEP activity may contribute to the development of AD by promoting the accumulation of A beta. The human NEP gene possesses four dinucleotide repeat polymorphisms, and it is possible that these polymorphisms regulate the NEP expression levels and influence the pathological cascade of AD. Therefore, we investigated the association of these polymorphisms with AD. We performed genotyping of each polymorphism in 201 Japanese sporadic AD patients and 208 Japanese controls. There were no significant differences between the AD and control groups in allele frequencies of each polymorphism. We conclude that these polymorphisms in the NEP gene do not contribute to genetic risk factors for sporadic AD.


Blood lipid levels, statin therapy and the risk of intracerebral hemorrhage.
Dyslipidemia has been proven to play an important role in the occurrence and development of the ischemic stroke and lipid-lowering therapy could significantly decrease the risk of the ischemic stroke. However, the association between lipid levels, lipid-lowering therapy and the risk of intracerebral hemorrhage (ICH) is not clear. Studies have shown that low serum levels of total cholesterol might be associated with increasing risk of ICH, whereas the SPARCL study, a large prospective, randomized, placebo-controlled trial, demonstrated an increased risk of hemorrhagic stroke during high-dose statin therapy among the patients with previous stroke. The relationship between lipid-lowering therapy and ICH has become a hot topic in the recent years. We searched PubMed for articles published in English to review the existing evidence on the association of lipid levels, statin therapy and risk of ICH as well as the underlying mechanisms in order to provide practical recommendations for clinical decision-making and a foundation for further researches.


Immunological identification of the karyophilic, histone-binding proteins N1 and N2 in somatic cells and oocytes of diverse amphibia.
A polypeptide pair designated N1/N2 (Mr 100 000 and 110 000) is an exceptionally acidic and abundant nuclear protein of oocytes of the toad, Xenopus laevis, and is characterized by a pronounced karyophilia. These proteins have been shown to form specific complexes with free, i.e., non-chromatin-bound histones H3 and H4 (Kleinschmidt & Franke, Cell 29 (1982) 799) [3]. In order to study these proteins and their possible counterparts in other species, antibodies were produced in guinea pigs against proteins N1/N2 purified from Xenopus oocyte nuclei. Using gel electrophoresis, peptide map analysis, immunoblotting techniques and immuno fluorescence microscopy the existence of polypeptides identical in Mr value and charge to polypeptide N1 of oocytes was demonstrated in cultured somatic cells of Xenopus laevis, where it was also highly enriched in cell nuclei, although the cellular concentration was much lower than in oocytes. A similar, if not identical protein, was recognized in nuclei of diverse other cell types including hepatocytes, enterocytes, ovarian follicle cells, and Sertoli cells of testis, of Xenopus, Rana temporaria, R. esculenta, Pleurodeles waltlii but not in erythrocytes and later stages of spermiogenesis. When nuclear proteins from oocytes of different amphibian species were examined with these antibodies it was found that the Mr values of N1/N2 proteins were considerably different in different species, ranging from Mr 110 000 to 190 000. Immunoprecipitation and gel electrophoretic analysis under non-denaturing conditions showed that a significant proportion of these proteins was contained in complexes with histones H3 and H4. The results demonstrate that proteins N1/N2 are not special proteins of oocytes of Xenopus laevis but occur in various other cells of diverse amphibian species. The widespread occurrence of these karyophilic proteins indicates that at least one function of these proteins, i.e., selective binding of the arginine-rich histones H3 and H4, is not exclusive to oocytes but may also contribute to the regulation of histone pools and chromatin formation in other cell types.


Bacterial avoidance of phagocytosis.
Phagocytosis constitutes the primary line of host innate and adaptive defence against incoming microbial pathogens, providing an efficient means for their removal and destruction. However, several virulent bacteria that do not function as intracellular pathogens have evolved mechanisms to avoid and prevent phagocytosis that constitute an essential part of their pathogenic capacity. Some of these mechanisms include preventing recognition by phagocytic receptors or blocking uptake by professional phagocytes. Recently, the molecular mechanisms of such antiphagocytic properties have been elucidated for some pathogens. Such mechanisms illustrate the diversity of mechanisms bacterial pathogens use to avoid phagocytic uptake.


Study on chemosensitivity of oral squamous cell carcinomas by histoculture drug response assay.
The aim of this study was to evaluate the reliability and utility of a histoculture drug response assay (HDRA) for treatment of squamous cell carcinoma in the oral cavity. Nineteen patients with squamous cell carcinoma of the oral cavity were assessed. Tumor tissue samples were histocultured on Gelfoam sponge gels in 24-well plates, followed by treatment with 5-fluorouracil (5-FU, 300 microg/ml), cisplatinum (CDDP, 20 microg/ml), 4-0-tetrahydropyranyl adriamycin (THP, 4.6 microg/ml), bleomycin (BLM, 20 microg/ml), adriamycin (ADM, 15 microg/ml) and docetaxel (TXT, 100 microg/ml). The controls were cultured without drug treatment. After completion of the culture, the relative cell survival in the tumors was determined using an MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide) assay. The inhibition rate was calculated, and sensitivity was defined as a tumor inhibition rate greater than 60% for 5-FU, 40% for TXT, and 50% for the other drugs. All cases were successfully evaluated by the HDRA, and no apparent relationships between the chemosensitivity test results and clinico-histopathological characteristics were seen. CDDP tended to be sensitive, whereas 5-FU, THP, and BLM tended to show resistance in many cases. A good correlation was obtained between the chemosensitivity test results and clinical response. In conclusion, HDRA is a useful method for selection of an anticancer agent for individual oral cancer patients, because of its ease of evaluation and high predictability.


HIV persistence in monocytes leads to pathogenesis and AIDS.
An hypothesis of the pathogenic mechanism leading to acquired immunodeficiency syndrome (AIDS) that places special emphasis on the potential for infected monocytes to act as the reservoir of a persistent human immunodeficiency virus (HIV) infection has been developed. Monocytes may mediate directly the infection and ultimate destruction of helper T cells; this establishes a direct relationship between antigen presentation and HIV dissemination, thus accounting for the cytopathogenic effects and immune system debilitation associated commonly with AIDS. The possibility that this mode of virus dissemination can account for the depletion of helper-T-cell subsets based on their antigen specificity is considered and may explain why the cellular immune response to the virus is ineffective. This concept and may also elucidate the role of intercurrent infections in the development of disease and it suggests mechanistic explanations for the conversion from prodromal to fulminant AIDS.


Is a head CT necessary after uncomplicated coiling of unruptured intracranial aneuryms?
In this study, we sought to determine whether routine head computed tomographies (CTs) after uncomplicated coil embolization of intracranial aneurysms can add any significant clinical value. We retrospectively reviewed the medical records of 139 patients with unruptured aneurysms who underwent 150 elective coiling procedures between January 2008 and June 2010. A total of 6 head CTs were obtained emergently after intraprocedural complications and 122 head CTs were obtained routinely after uncomplicated coil embolization of intracranial aneurysms. The 122 head CTs that were obtained routinely after uncomplicated coil embolization of unruptured intracranial aneurysms did not show any acute or subacute changes. A head CT after uncomplicated coil embolization of an intracranial aneurysm does not add any significant clinical value and should not be ordered routinely.


Verotoxin-producing Escherichia coli (VTEC) and eae-positive non-VTEC in 1-30-days-old diarrhoeic dairy calves.
Faecal samples from 221, 1-30-days-old, diarrhoeic dairy calves were screened for the presence of verotoxin-producing Escherichia coli (VTEC) and eae-positive non-VTEC. Calves were grouped according to their age (1-7, 8-14, 15-21 and 22-30 days) and analyses of prevalences were done by Mantel-Haenzsel chi 2-test for trend. VTEC and eae-positive non-VTEC were detected in 20 (9.0%) and 18 (8.1%) of the diarrhoeic calves, respectively. A significant age-associated increase in the prevalence of VTEC (p = 0.0001), but not in the prevalence of eae-positive non-VTEC (p = 0.381), was found. Significant differences in VTEC prevalence were found between the age-group 22-30 days and in all other age-groups. 43 (5.0%) of the 861 E. coli isolates from the 221 diarrhoeic calves were VTEC, and 30 (69.8%) of these strains produced VT1 only. More than one-half of the VTEC strains (55.8%) were positive for the eae gene and all these eae-positive VTEC strains produced VT1 only. A high percentage (76.7%) of VTEC strains belonged to E. coli serogroups (O4, O26, O39, O91, O113, O128 and O145) associated with haemorrhagic colitis and haemolytic uraemic syndrome in humans. 51 (5.9%) of the E. coli strains studied were eae-positive non-VTEC and the serogroups most prevalent among these strains were O4, O14, O26 and O123. Only four of the eae-positive strains were also espB-positive by hybridization with a probe from a human EPEC isolate and none of these strains produced VT.


Role of radiotherapy in the management of vulvar cancer: Recommendations of the French society for radiation oncology.
Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.


Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway.
Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism of serine/arginine repetitive matrix protein 2-alternative splicing (SRRM2-AS) in NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially expressed lncRNAs were screened out via microarray analysis. Vascular endothelial growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined in NPC and adjacent tissues. NPC CNE-2 cells were treated with a series of vector and small interfering RNA to explore the effect of SRRM2-AS in NPC. The target relationship between myosin light chain kinase (MYLK) and SRRM2-AS was verified. Levels of SRRM2-AS, MYLK, cGMP, PKG, VEGF, PCNA, Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect of SRRM2-AS on cell proliferation, colony formation, angiogenesis, cell cycle, and apoptosis in NPC was evaluated. SRRM2-AS was highly expressed and MYLK was poorly expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC tissues. MYLK was confirmed to be a target gene of SRRM2-AS. Silencing of SRRM2-AS elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF, PCNA, Ki-67, and Bcl-2. Especially, silencing of SRRM2-AS suppressed cell proliferation, colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis in NPC. Our results suggested that silencing of SRRM2-AS protected against angiogenesis of NPC cells by upregulating MYLK and activating the cGMP-PKG signaling pathway, which provides a new target for NPC treatment.


Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich's ataxia: an open-label trial.
Minimal objective evidence exists regarding management of Friedreich's ataxia (FRDA). Antioxidant and recombinant human erythropoietin therapies have been considered potential treatments to slow progression of FRDA in a small number of studies. The primary objective of the current study was to test the efficacy, safety, and tolerability of triple therapy-darbepoetin alfa, idebenone, and riboflavin-in FRDA in a clinical pilot study. Patients included in this study were nine females, 16 to 45 years of age (average 28 ± 8), diagnosed with FRDA with confirmed GAA repeat expansion mutations in the FXN gene and a GAA repeat ≥400 on the shorter allele. Patients had a baseline score between 8 and 28.5 (average 20.7 ± 8.3) on the scale for the assessment and rating of ataxia and 94.3 ± 27.2 g/m(2) in left ventricular mass index (LVMI). Patients had been treated with triple therapy with 150 μg darbepoetin alfa every 2 or 3 weeks, 10-20 mg/kg/day idebenone, and 10-15 mg/kg/day riboflavin for 32 ± 19.4 months (range of 8-56 months). Triple therapy was tolerated. Although not statistically significant, improvement of ataxia was observed during the first six 4-month periods of the study. Furthermore, a small decrease in disease progression during the first 2 years of treatment was observed. Long-term statistically nonsignificant improvement of LVMI and stability of the echocardiographic parameters could be considered. Triple therapy may slow disease progression of FRDA.


A review on polyester and polyester-amide thin film composite nanofiltration membranes: Synthesis, characteristics and applications.
Nanofiltration (NF) membranes have been widely used in various fields including water treatment and other separation processes, while conventional thin film composite (TFC) membranes with polyamide (PA) selective layers suffer the problems of fouling and chlorine intolerance. Due to the abundant hydrophilic hydroxyl groups and ester bonds free from chlorine attack, the TFC membranes composed of polyester (PE) or polyester-amide (PEA) selective layers have been proven to possess enhanced anti-fouling properties and superior chlorine resistance. In this review, the research progress of PE and PEA nanofiltration membranes is systematically summarized according to the variety of hydroxyl-containing monomers for membrane fabrication by the interfacial polymerization (IP) reaction. The synthesis strategies as well as the mechanisms for tailoring properties and performance of PE and PEA membranes are analyzed, and the membrane application advantages are demonstrated. Moreover, current challenges and future perspectives of the development of PE and PEA nanofiltration membranes are proposed. This review can offer guidance for designing high-performance PE and PEA membranes, thereby further promoting the efficacy of nanofiltration.


Evaluation of salivary Thy-1 in health, periodontitis, and obesity.
Thy-1 (CD90) is a glycosylphosphatidyl-anchored protein belonging to the immunoglobulin family and is known to control mesenchymal stromal cells differentiation into osteoblasts or adipocytes. The study aimed to investigate the salivary levels of Thy-1 in health, periodontitis, obesity, and any potential association. Seventy-one participants were divided into four groups: healthy (H), subjects with periodontitis (P), obese individuals (O), and obese individuals having periodontitis (PO). Unstimulated whole saliva was collected from participants who were evaluated for periodontal parameters. The levels of Thy-1 were measured with a commercially available ELISA kit. The data were statistically analyzed. A significant difference in salivary Thy-1 levels among different groups was observed. Periodontitis patients had the maximum, and obese individuals had the minimum Thy-1 levels. Significant differences between H and P, H and PO, P and O, and O and PO were observed. Overall correlations between Thy-1 and periodontal parameters and a positive correlation with pocket depth in group PO were noted. Thy-1 could be detected in the saliva of all study participants. It is implied that a local inflammatory condition like periodontitis elevates the salivary levels of Thy-1 with, and without obesity.


Relation of positive T wave in lead aVR to risk of cardiovascular mortality.
We examined the prevalence and prognostic impact of a positive T wave in lead aVR (aVRT+) on a standard electrocardiogram in the general population. Data were collected from a large nationally representative (random sample) health examination survey conducted in Finland from 2000 through 2001. The survey consisted of 6,354 subjects (2,876 men and 3,478 women) ≥30 years who participated in the field health examination including standard electrocardiographic (ECG) recording at rest. The prevalence of aVRT+ (defined as positive or isoelectric T wave in lead aVR) was 2.2%. During the median follow-up of 98.5 months (interquartile range 96.6 to 99.6), there were 214 (3.5%) cardiovascular (CV) deaths. In Cox regression analysis after adjustment for age and gender, relative risks for CV and total mortalities associated with aVRT+ were 3.24 (95% confidence interval [CI] 2.32 to 4.54, p <0.001) and 1.91 (95% CI 1.47 to 2.49, p <0.001), respectively. In the fully adjusted model controlling for other risk factors, CV morbidity, and ECG findings, the relative risk for CV mortality for aVRT+ was 2.94 (95% CI 2.07 to 4.18, p <0.001). In conclusion, aVRT+, an easily recognized ECG finding, predicts risk for CV mortality in the general population. This finding could aid in screening for risk of total and CV mortalities.


Epidemiology of asthma in the United States.
Incidence and prevalence rates of asthma can vary greatly according to population and location. The National Heart and Blood Institute of the National Institutes of Health defines asthma as a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. This article uses the most common definitions and diagnostic methods for asthma. In 2009 there were 2.1 million asthma-related emergency department (ED) visits. ED visits lend an opportunity for providers to identify and intervene in the care of patients whose asthma is poorly controlled.


Gold-Catalyzed Annulation of 1,8-Dialkynylnaphthalenes: Synthesis and Photoelectric Properties of Indenophenalene-Based Derivatives.
A simple gold-catalyzed annulation of 1,8-dialkynylnaphthalenes utilizing a cationic gold catalyst was developed. Such a peri-position of two alkynyl substituents has not been studied in gold catalysis before. Dependent on the substrate, the reactions either follow a mechanism involving vinyl cation intermediates or involve a dual gold catalysis mechanism which in an initial 6-endo-dig-cyclization generates gold(I) vinylidene intermediates that are able to insert into C-H bonds. Indenophenalene derivatives were obtained in moderate to high yields. In addition, the bidirectional gold-catalyzed annulation of tetraynes provided even larger conjugated π-systems. The optoelectronic properties of the products were also investigated.


A small molecule Smac-mimic compound induces apoptosis and sensitizes TRAIL- and etoposide-induced apoptosis in breast cancer cells.
Inhibitor of apoptosis protein (IAP) suppresses apoptosis through binding and inhibiting active caspases-3, -7 and -9 via its baculoviral IAP repeat (BIR) domains. During apoptosis the caspase inhibition by IAPs can be negatively regulated by a mitochondrial protein second mitochondrial-derived activator of caspase (Smac). Smac physically interacts with multiple IAPs and relieves their inhibitory effect on caspases-3, -7 and -9. Recently, a small molecule Smac-mimic compound (Smac-mimic), which potentiates TNF-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-alpha mediated cell death in glioblastoma T98G cells and HeLa cells, was identified and characterized. To determine the efficacy of this compound in breast cancer cells, we first measured protein expression of three IAPs: XIAP, cIAP-1, and cIAP-2 in nine independent breast cancer cell lines. Three cell lines were chosen: a high IAPs expressing line MDA-MB-231, and two low IAPs expressing lines, T47D and MDA-MB-453. The cell lines were tested for their sensitivity to Smac-mimic alone or in combination with TRAIL or etoposide. Acting alone, Smac-mimic was quite potent with a cytotoxic IC50 of 3.8 nM in high IAPs expressing MDA-MB-231 cells, but was inactive at a much higher concentration in low IAPs expressing T47D and MDA-MB-453 cells. In fact, as low as 2.5 nM of Smac-mimic alone was sufficient to activate caspase-3 and induce apoptosis in MDA-MB-231 cells. In combinational treatments with TRAIL or etoposide, Smac-mimic significantly sensitized cells to growth suppression in MDA-MB-231 cells, but to a lesser extent in T47D and MDA-MB-453 cells. Furthermore, it significantly synergized MDA-MB-231, but not T47D cells to apoptosis induced by either TRAIL or etoposide. Thus, in these cell lines, Smac-mimic acts in an apparent IAPs dependent manner to induce apoptosis alone as well as sensitizes breast cancer cells to TRAIL or etoposide induced apoptosis via caspase-3 activation.


Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa.
The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa, coupled with shrinking antibiotic pipelines, has increased the demand for new antimicrobials with novel mechanisms of action. As the indiscriminate nature of broad-spectrum antimicrobial toxicity may have negative clinical consequences and increase the incidence of resistance, we have developed a P. aeruginosa-selective antimicrobial peptide capable of preferentially killing P. aeruginosa relative to benign microorganisms. A targeting peptide (PA2) that binds specifically to OprF porin on P. aeruginosa was identified by phage display peptide library screening, and a hybrid peptide was constructed by addition of the targeting peptide to GNU7, a potent antimicrobial peptide. The resulting hybrid peptide PA2-GNU7 exhibited potent antimicrobial activity against P. aeruginosa without causing host toxicity. Confocal laser scanning microscopy analysis and time-kill experiments demonstrated that PA2-GNU7 exhibited a high degree of specificity for P. aeruginosa, and rapidly and selectively killed P. aeruginosa cells in mixed cultures. In addition, in vivo treatment efficacy of PA2-GNU7 was significantly greater than that of conventional antibiotics in a mouse model of MDR P. aeruginosa infection. Taken together, the data suggest that PA2-GNU7 may be a promising template for further development as a novel anti-MDR P. aeruginosa therapeutic agent.


Inhibition of microRNA-30a alleviates vascular remodeling in pulmonary arterial hypertension.
The excessive and ectopic pulmonary artery smooth muscle cells (PASMCs) are crucial to the pathogenesis of pulmonary arteriole (PA) remodeling in pulmonary arterial hypertension (PAH). We previously found that microRNA (miR)-30a was significantly increased in acute myocardial infarction (AMI) patients and animals, as well as in cultured cardiomyocytes after hypoxia, suggesting that it might be strongly associated with hypoxia-related diseases. Here, we investigated the role of miR-30a in the PASMC remodeling of PAH. The expression of miR-30a was higher in the serum of PAH patients compared with healthy controls. miR-30a was mainly expressed in PAs and was increased in PASMCs after hypoxia, mediating the downregulation of p53 tumor suppressor protein (P53). Genetic knockout of miR-30a effectively decreased right ventricular (RV) systolic pressure (RVSP), PA, and RV remodeling in the Su5416/hypoxia-induced and monocrotaline (MCT)-induced PAH animals. Additionally, pharmacological inhibition of miR-30a via intratracheal liquid instillation (IT-L) delivery strategy showed high efficiency, which downregulated miR-30a to mitigate disease phenotype in the Su5416/hypoxia-induced PAH animals, and these beneficial effects could be partially reduced by simultaneous P53 inhibition. We demonstrate that inhibition of miR-30a could ameliorate experimental PAH through the miR-30a/P53 signaling pathway, and the IT-L delivery strategy shows good therapeutic outcomes, providing a novel and promising approach for the treatment of PAH.


Hyperkalemia with concomitant watery diarrhea: an unusual association.
Four patients presented to the emergency room with life-threatening hyperkalemia and concomitant watery diarrhea. Hypovolemia, acidosis, and renal insufficiency were present in all 4 cases. In 2 patients, hyperkalemia followed initiation of angiotensin-converting enzyme (ACE) inhibitor therapy, whereas 1 patient experienced hyperkalemia after a dose increase of an ACE inhibitor, and the fourth patient was on continuous ACE-inhibitor therapy at the time of the hyperkalemia episode. Two of the 3 patients with functioning kidneys required hemodialysis to correct the hyperkalemia, whereas the other patient was on long-term hemodialysis therapy. In the 2 patients in whom transtubular potassium (K+) gradients were available, their values ranged far below normal, indicating tubular failure to secrete K+. This abnormality was attributed to decreased distal delivery of sodium and water and to renin/angiotensin II/aldosterone blockade. It has been proposed that aldosterone blockade impairs the capacity of the colonic epithelial cells to secrete K+. In all 4 patients the watery diarrhea ceased in parallel with the correction of serum K+ to normal values. It is suggested that hyperkalemia, most likely by stimulating intestinal motility, induced the watery diarrhea in all 4 patients. The watery diarrhea, however, failed to compensate for the renal tubular failure to secrete K+.


[Prevention of thrombosis by Hemoclar. Preliminary results of a test in a patient with antithrombin III deficiency].
We report here preliminary results of a study comparing the effect of Hemoclar and antithrombin III (AT III) in a patient with an AT III congenital deficiency. Both drugs inhibit thrombin generation in the patient's plasma. Unlike AT III, Hemoclar also inhibits factor Xa generation. This led us to propose the use of Hemoclar, which acts via an AT III independent pathway, to prevent thrombosis in A III deficient patients.


Severe loss of vision after removal of cataract caused by intravitreal triamcinolone in combination with photodynamic therapy for exudative age-related macular degeneration.
Intravitreal triamcinolone has been suggested as an adjunctive to photodynamic therapy in the treatment of exudative macular degeneration. One of the side-effects of intravitreal triamcinolone is the development of cataract, and it is known that cataract extraction can exacerbate macular degeneration. A case is presented where combined intravitreal triamcinolone and photodynamic therapy stopped the progression of the exudative macular degeneration. Subsequent progression of cataract required cataract extraction, which resulted in a very rapid progression of the exudative macular degeneration and loss of vision.


Redescription of the pupa of Culex (Culex) declarator Dyar and Knab (Diptera, Culicidae), with amendments to key to the Culex pupae of the eastern United States.
The pupa of Culex declarator was partially described and illustrated by Lane. This species was recently discovered in Florida for the first time and a series of individual rearings have resulted in a number of pupae and an opportunity to redescribe it fully, with a complete illustration. Amendment to the key to the Culex pupae of the eastern United States is provided.


The result of prospective evaluation of 3-dimensional printing-aided extensive thoracoabdominal aorta repair.
Paraplegia is a distressing complication after open thoracoabdominal aortic aneurysm (TAAA) repair, and revascularization of T8-L2-level segmental arteries is considered pivotal to prevent paraplegia. We employed 3-dimensional (3D) printing to efficiently revascularize segmental/visceral arteries and prospectively evaluated its safety and efficacy. From January 1, 2020, to June 30, 2022, we prospectively enrolled patients of extent I, II, or III TAAA repair. Guidance models were 3D-printed based on preoperative computed tomography, and multibranched aortic grafts were manually constructed upon this model before surgery. The composite outcome of operative mortality, permanent stroke, and permanent spinal cord deficit (SCD) was compared with the historical control group (n = 77, in 2015-2020), subjected to similar TAAA repair without 3D printing. A total of 38 patients (58.6 ± 13.2 years) underwent open TAAA repair with the aid of 3D printing. Extent I, II, and III repairs were performed in 14 (36.8%), 17 (44.7%), and 7 (18.4%), respectively. Concomitant arch repair and bi-iliac reconstruction were performed in 7 (18.4%) and 6 patients (15.8%), respectively. Mean pump time was 107.7 ± 55.5 minutes. Operative mortality, permanent stroke, and permanent SCD each occurred in 1 patient (2.6%), and the incidence of the composite outcome was 7.9% (3/38). In the control group, mean pump time was 166.0 ± 83.9 minutes, significantly longer than the 3D-printing group (P < .001), and operative mortality, permanent stroke, permanent SCD, and the composite outcome occurred in 7 (9.1%), 9 (11.7%), 8 (10.4%), and 19 (24.7%), respectively. Open repairs of extensive TAAA with 3D printing showed favorable safety and efficacy, which need further validation by larger studies.


Developmentally regulated subnuclear genome reorganization restricts neural progenitor competence in Drosophila.
Stem and/or progenitor cells often generate distinct cell types in a stereotyped birth order and over time lose competence to specify earlier-born fates by unknown mechanisms. In Drosophila, the Hunchback transcription factor acts in neural progenitors (neuroblasts) to specify early-born neurons, in part by indirectly inducing the neuronal transcription of its target genes, including the hunchback gene. We used in vivo immuno-DNA FISH and found that the hunchback gene moves to the neuroblast nuclear periphery, a repressive subnuclear compartment, precisely when competence to specify early-born fate is lost and several hours and cell divisions after termination of its transcription. hunchback movement to the lamina correlated with downregulation of the neuroblast nuclear protein, Distal antenna (Dan). Either prolonging Dan expression or disrupting lamina interfered with hunchback repositioning and extended neuroblast competence. We propose that neuroblasts undergo a developmentally regulated subnuclear genome reorganization to permanently silence Hunchback target genes that results in loss of progenitor competence.


A simple and inexpensive system for monitoring jaw movements in ambulatory humans.
A simple and inexpensive method for recording vertical movements of the human mandible relative to the maxilla is presented. Measurements are made from accelerometers and a Hall-effect device temporarily glued to the upper and lower anterior teeth. The accelerometer signals are integrated once to give velocity and a second time to give position. Movements of the mandible relative to the maxilla are obtained by integrating the difference between the two accelerometer signals. The (relative) velocity and position records derived in this way are linear, but subject to drift when the jaw is stationary. Steady mandibular position is obtained from the Hall-effect system, but this signal must be corrected for its inherent non-linearity. This device can record rapid movements of the mandible even when the head is unrestrained, and interferes minimally with normal jaw movements.


Fusion of synaptic vesicle membranes with planar bilayer membranes.
The interaction of synaptic vesicles with horizontal bilayer lipid membranes (BLMs) was investigated as a model system for neurotransmitter release. High concentrations (200 mM) of the fluorescent dye, calcein, were trapped within synaptic vesicles by freezing and thawing. In the presence of divalent ions (usually 15 mM CaCl2), these frozen and thawed synaptic vesicles (FTSVs) adhere to squalene-based phosphatidylserine-phosphatidylethanolamine BLMs whereupon they spontaneously release their contents which is visible by fluorescence microscopy as bright flashes. The highest rate of release was obtained in KCl solutions. Release was virtually eliminated in isotonic glucose, but could be elicited by perfusion with KCl or by addition of urea. The fusion and lysis of adhering FTSVs appears to be the consequence of stress resulting from entry of permeable external solute (KCl, urea) and accompanying water. An analysis of flash diameters in experiments where Co+2, which quenches calcein fluorescence, was present on one or both sides of the BLM, indicates that more than half of the flashes represent fusion events, i.e., release of vesicle contents on the trans side of the BLM. A population of small, barely visible FTSVs bind to BLMs at calcium ion concentrations of 100 microM. Although fusion of these small FTSVs to BLMs could not be demonstrated, fusion with giant lipid vesicles was obvious and dramatic, albeit infrequent. Addition of FTSVs or synaptic vesicles to BLMs in the presence of 100 microM-15 mM Ca2+ produced large increases in BLM conductance. The results presented demonstrate that synaptic vesicles are capable of fusing with model lipid membranes in the presence of Ca+2 ion which, at the lower limit, may begin to approach physiological concentrations.


Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.
Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.


Abasic sites from cytosine as termination signals for DNA synthesis.
DNA with abasic sites has been prepared by deamination of cytosine followed by treatment of the product with uracil N-glycosylase. Termination in vitro on such templates does not occur until treatment with uracil N-glycosylase. DNA terminated one base before abasic sites created from C's has been used as a template in "second stage" reactions. With enzymes devoid or deficient in 3' greater than 5' exonuclease activity purines, particularly adenine, are preferentially added opposite the putative abasic site. 2-Aminopurine behaves more like adenine than like guanine in these experiments. Polymerase beta preferentially incorporates A opposite abasic sites produced from T, and G opposite abasic sites produced from C. We have eliminated an obvious artefact (e.g. strand switching) which might account for this observation.


Association between use of electronic vaping products and insufficient sleep among adolescents: Findings from the 2017 and 2019 YRBS.
Although studies have investigated the association between cigarette smoking and sleep outcomes among adolescents in the United States, few studies have examined the association between electronic vaping products (EVPs) use and insufficient sleep among adolescents. The objective of this study was to investigate the cross-sectional association between the use of EVPs and insufficient sleep among adolescents. Data were pooled from the 2017 and 2019 Youth Risk Behavior Survey. An analytic sample of 28,135 adolescents (51.2% female) was analyzed using binary logistic regression. The dependent variable investigated was insufficient sleep, and the main independent variable was the use of EVPs. Of the 28,135 adolescents, 22.6%, 19.2%, and 58.2% were current, former, and never users of EVPs, respectively. More than three in four adolescents (76.5%) did not obtain the recommended 8 h of sleep on an average school night. Controlling for demographic factors and other covariates, adolescents who currently used EVPs had 1.33 times higher odds of having insufficient sleep (AOR = 1.33, p < .001, 95% CI = 1.16-1.52), and adolescents who previously used EVPs had 1.29 times higher odds of having insufficient sleep (AOR = 1.29, p < .001, 95% CI = 1.15-1.44) when compared to adolescents who had never used EVPs. Adolescents were more likely to get insufficient sleep if they were older, non-Hispanic Black, had symptoms of depression, experienced suicidal ideation, engaged in excessive screen-time behaviors, or currently used alcohol. Physical activity had a protective effect on insufficient sleep. This study found that EVPs use was associated with insufficient sleep among adolescents over and above demographic and other covariates. As EVP use increases among adolescents, it is important to consider the potential impact on multiple domains, including sleep. Future studies that employ longitudinal designs may offer additional insight into the mechanisms underlying the association between EVPs use and insufficient sleep.


Comparison of various classification techniques for supervision of milk processing.
Detecting the types of anomalies that can occur throughout the milk processing process is an important task since it can assist providers in maintaining control over the process. The Raman spectrometer was used in conjunction with several classification approaches-linear discriminant analysis, decision tree, support vector machine, and k nearest neighbor-to establish a viable method for detecting different types of anomalies that may occur during the process-temperature and fat variation and added water or cleaning solution. Milk with 5% fat measured at 10°C was used as the reference milk for this study. Added water, cleaning solution, milk with various fat contents and different temperatures were used to detect abnormal conditions. While decision trees and linear discriminant analysis were unable to accurately categorize the various type of anomalies, the k nearest neighbor and support vector machine provided promising results. The accuracy of the support vector machine test set and the k nearest neighbor test set were 81.4% and 84.8%, respectively. As a result, it is reasonable to conclude that both algorithms are capable of appropriately classifying the various groups of samples. It can assist milk industries in determining what is wrong during milk processing.


Effects of superabundant food on breeding success and behavior of the red-winged blackbird.
The effects of food on breeding success and behavior of the red-winged blackbird (Icteridae: Agelaius phoeniceus) were investigated during 3 successive breeding seasons. In the second season, a 4-week pulse of abundant food in the form of a periodical cicada emergence (Homoptera: Cicadidae: Magicicada spp.) occurred in the forest adjacent to the marsh where the birds were breeding.During the cicada period, the bird population showed: 1) an increase in foraging trips to the forest and a decrease in trips per h, 2) increased biomass of nestlings, 3) increased nestling survival caused by decreased starvation, 4) increased fledging success, and 5) bimodal weight distributions of older nestlings (reflective of the sexual dimorphism in this species). These data suggest the temporary removal of food limitations on the breeding population when the pulse of food was available.


High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study.
Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect. To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome. Cross-sectional comparison. University hospital in Lausanne, Switzerland. 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated. Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype. Hyperresponders and nonresponders had similar pretreatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene. Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.


Effects of trophic morphology and behavior on foraging rates of three Hawaiian honeycreepers.
The effects of trophic morphology and behavior of three Hawaiian honeycreepers (Fringillidae: Drepanidinae) upon their foraging rates on the flowers of Vaccinium calycinum are examined. The Maui Creeper (Paroreomyza montana), the Amakihi (Hemianathus virens), and the I'iwi (Vestiaria coccinea) show shifts from a short straight bill to a long decurved bill, from a tongue adapted for insect feeding to one specialized for nectar, and diets ranging from primarily probing for insects to primarily nectarivorous. This diversity is examined feeding on the simple straight tubular corollas of the Vaccinium. Significant differences (P<0.001, t-tests) exist among the birds with respect to foraging rates on these flowers. The I'iwi, with its greatly decurved (64°) bill feeds the quickest (2.09 s/flower) while the Maui Creeper with its rather straight (18°) bill feeds the slowest (3.87 s/flower). These differences are seen to be the result of differing abilities of tongues to extract nectar as well as differing behavioral tactics of floral exploration and nectar extraction. This suggests that predictions of foraging efficiency based solely on bill morphology are not necessarily valid, and that other factors (tongue morphology, foraging maneuvers, and typical food spectrum) must also be considered.


Recurrent extensive plunging ranula: A rare case.
Plunging ranula (PR) is a cystic mass presenting on the lateral side of the neck with or without a history of the usual presentation of an intraoral lesion. "PR" is recognized as an uncommon lesion that has been found predominantly in the third decade of life mostly in males. However, the exact prevalence of "PR" is not yet known. We report a rare case of an extensive PR that reached the parapharyngeal space in a 17-year-old Saudi female. The diagnosis was made when she presented to the ENT clinic with swellings in the right submandibular and right floor of the mouth. The diagnosis of "PR" with the absence of an oral lesion is very challenging and requires a detailed history, clinical examination, and radiological imaging. Different modalities of treatment have been discussed. However, the excision of ranula and the sublingual gland is the most effective way of management.


Runs of homozygosity reveal signatures of positive selection for reproduction traits in breed and non-breed horses.
Modern horses represent heterogeneous populations specifically selected for appearance and performance. Genomic regions under high selective pressure show characteristic runs of homozygosity (ROH) which represent a low genetic diversity. This study aims at detecting the number and functional distribution of ROHs in different horse populations using next generation sequencing data. Next generation sequencing was performed for two Sorraia, one Dülmen Horse, one Arabian, one Saxon-Thuringian Heavy Warmblood, one Thoroughbred and four Hanoverian. After quality control reads were mapped to the reference genome EquCab2.70. ROH detection was performed using PLINK, version 1.07 for a trimmed dataset with 11,325,777 SNPs and a mean read depth of 12. Stretches with homozygous genotypes of >40 kb as well as >400 kb were defined as ROHs. SNPs within consensus ROHs were tested for neutrality. Functional classification was done for genes annotated within ROHs using PANTHER gene list analysis and functional variants were tested for their distribution among breed or non-breed groups. ROH detection was performed using whole genome sequences of ten horses of six populations representing various breed types and non-breed horses. In total, an average number of 3492 ROHs were detected in windows of a minimum of 50 consecutive homozygous SNPs and an average number of 292 ROHs in windows of 500 consecutive homozygous SNPs. Functional analyses of private ROHs in each horse revealed a high frequency of genes affecting cellular, metabolic, developmental, immune system and reproduction processes. In non-breed horses, 198 ROHs in 50-SNP windows and seven ROHs in 500-SNP windows showed an enrichment of genes involved in reproduction, embryonic development, energy metabolism, muscle and cardiac development whereas all seven breed horses revealed only three common ROHs in 50-SNP windows harboring the fertility-related gene YES1. In the Hanoverian, a total of 18 private ROHs could be shown to be located in the region of genes potentially involved in neurologic control, signaling, glycogen balance and reproduction. Comparative analysis of homozygous stretches common in all ten horses displayed three ROHs which were all located in the region of KITLG, the ligand of KIT known to be involved in melanogenesis, haematopoiesis and gametogenesis. The results of this study give a comprehensive insight into the frequency and number of ROHs in various horses and their potential influence on population diversity and selection pressures. Comparisons of breed and non-breed horses suggest a significant artificial as well as natural selection pressure on reproduction performance in all types of horse populations.


Acid pre-adaptation enhances virulence of Salmonella enterica serovar Typhimurium dam mutant.
It is well established that success or failure of bacterial pathogens during infection relies upon its ability to overcome many lethal environments in the host such as acidity, osmolarity and bile salts. In the present study, we have studied the effects of acid adaptation on the virulence of Salmonella enterica serovar Typhimurium dam mutant. Our results indicated that LD(50) of adapted strains were lower than those of control strains. Also, the in vivo assays have shown that the development of a systemic infection is slower for control strains than for adapted strains. In addition, the number of acid-adapted mutants colonizing spleen and liver is higher than control strains. Adhesion and invasion experiments were performed in order to compare the pathogenicity of Salmonella. No significant differences were shown between pre-treated and non-adapted strains. According to these results, we report that acid adaptation of Salmonella enterica serovar Typhimurium dam mutants can increase their in vivo virulence in mice.


Quantitative evaluation of learning and memory trace in studies of mnemotropic effects of immunotropic drugs.
Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.


Appraisal of GABA and PABA as linker: design and synthesis of novel benzamide based histone deacetylase inhibitors.
Histone deacetylase inhibitors have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Two novel series of N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}-butyramide and N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}benzamide were designed and synthesized as novel histone deacetylase inhibitors. The anticancer potential of the compounds were determined in-vitro using MTT assay against HCT-116 and U251 (glioma) cell lines and histone deacetylase inhibitory assay. The synthesized compounds were investigated for anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The efforts were also made to ascertain structure-activity relationships among test compounds. The results of the present studying represents appraisal of γ-aminobutyric acid (GABA) and para-aminobenzoic acid (PABA) as linker moiety for development of newer benzamide based histone deacetylase inhibitor.


Early ceremonial constructions at Ceibal, Guatemala, and the origins of lowland Maya civilization.
The spread of plaza-pyramid complexes across southern Mesoamerica during the early Middle Preclassic period (1000 to 700 BCE) provides critical information regarding the origins of lowland Maya civilization and the role of the Gulf Coast Olmec. Recent excavations at the Maya site of Ceibal, Guatemala, documented the growth of a formal ceremonial space into a plaza-pyramid complex that predated comparable buildings at other lowland Maya sites and major occupations at the Olmec center of La Venta. The development of lowland Maya civilization did not result from one-directional influence from La Venta, but from interregional interactions, involving groups in the southwestern Maya lowlands, Chiapas, the Pacific Coast, and the southern Gulf Coast.


Identification of Natural CRISPR Systems and Targets in the Human Microbiome.
Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.


Preparation of tyrosinase inhibitors and antibrowning agents using green technology.
Chalcones and their derivatives have attracted great interests in recent years for their comprehensive biological activities. In this study, 2,4,2',4'-tetrahydroxychalcone and its two derivatives, 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione (new compound) and 7,2',4'-trihydroxyflavanone, were synthesized through one-pot green procedure catalyzed by boric acid in polyethylene glycol 400. Their structures were identified by ESI-MS and NMR spectral. Tyrosinase inhibitory activity and antibrowning test results showed that compounds 1-3 exhibited strong tyrosinase inhibitory activities and significant antibrowning effects on the fresh-cut lotus root slices at room temperature in 48 h. Among them, 0.01% 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione combined with 0.5% VC showed the best antibrowning ability. In brief, this study offers a protocol for one-pot green synthesis of high efficiency tyrosinase inhibitors which may be suitable as antibrowning agents for fresh-cut vegetables. More important, this study developed a new type of 1,5-dione derivative which may serve as new lead structures for novel tyrosinase inhibitors discovery.


Differential impairment of psychomotor efficiency and processing speed in patients with chronic kidney disease.
Cognitive impairment has been documented in patients with chronic kidney disease. In a recent paper, improvements in cognitive function were seen in hemodialysis (HD) patients switched from conventional HD to nocturnal HD, in two of three domains of cognitive function. Based on these findings, we hypothesized that functional decline may occur differentially in some domains more than others. Using a cross-sectional study design, patients optimized on medical treatment at a predialysis clinic were tested using a battery of neuropsychological (NP) tests measuring three domains of cognitive functioning-attention & working memory skills; psychomotor efficiency & processing speed; and learning efficiency. Clinical subjective symptoms for cognitive functioning and depression were measured using the Patient's Assessment of Own Functioning (PAOF) inventory and the Beck Depression Inventory (BDI). One hundred and three patients aged 64.6+/-12.4 years were recruited. Of these, 40% were diabetic, with a mean Charlson comorbidity score of 4.4+/-2.1. Depression (defined as >16 on the BDI score) was seen in 11 patients. After adjustment for comorbid diseases, hemoglobin, the use of neurodepressor medication, and parathyroid hormone (PTH) values, renal function was negatively correlated with psychomotor efficiency & processing speed, but not with attention & working memory or learning efficiency scores. Chronic kidney disease is associated with a decline in psychomotor efficiency & processing speed, but not with attention & working memory or learning efficiency.


Physical abuse of abandoned children in India.
Child abuse and neglect, though existing in India, has not come to light because of underlying social constraints like poverty, malnutrition and infection. With an intention to study the problem of physical abuse in neglected children, patients admitted to the pediatric wards of our institution, predominantly with some form of physical abuse were specifically looked for from January 1976 onwards. Over a period of 4 1/2 years, 18 such cases were encountered. Most of the babies were less than four weeks of age, were predominantly females, were quite often premature or malnourished, and rarely had a physical deformity. These babies were deserted and later were found by police or social workers in gutters, dustbins, garbage tins, railway platforms, etc. The spectrum of abuse and injuries included newborn babies with intact placenta, at times lacerated, strangling marks on the throat, multiple bruises, bleeding from the umbilicus, avulsion of the scalp with severe bleeding, shock as a result of environmental stress (i.e., hypothermia), evidence of infection, rat bite marks, and fractures. The morbidity was very high, ultimately resulting in 88.9% mortality over varying periods of time, maximum survival being 22 days. The motive behind this abuse always was an unwanted baby.


Risk Communication Through Health Beliefs for Preventing Opisthorchiasis-Linked Cholangiocarcinoma: A Community- Based Intervention in Multicultural Areas of Thailand.
This research aimed to study the effects of the risk communication program through the Cambodian folk song to prevent Opisthorchiasis-linked cholangiocarcinoma (OV-CCA). We conducted the quasi-experimental research between August and December 2017 in the Cambodian communities, one-fourth of ethnic minorities residing in multicultural areas of Sisaket Province, Thailand. The samples consisted of 94 equally people divided into experimental group and control group. The experimental group included 47 people at-risk of OV-CCA who received the program for 12 weeks, while the control group received regular services. We collected data by using a questionnaire with a reliability of 0.93. Descriptive and inferential statistics were used for data analysis. The study indicated that the socioeconomic information of both groups was not different. The mean scores of all issues (health beliefs, social support, and prevention behavior in the experimental group were higher than those of the control group with statistical significance. Closer inspection showed that the mean difference of the health beliefs was 55.61 points (95%CI: 52.39-57.42, p<0.001), social support was 9.09 points (95%CI: 8.12-10.05, p<0.001), and prevention behavior was 6.38 points (95%CI: 5.43-7.33, p<0.001). Through the Cambodian folk song, the risk communication program by applying the health beliefs and social support to prevent OV-CCA is beneficial for behavior modification in areas with similar cultures.


A case of giant left main coronary artery aneurysm in an elderly man.
Aneurysms of the left main coronary artery are rare and their optimal treatments remain unknown. A 64-year-old man without any symptoms was referred to our department for suspected coronary aneurysm. Transthoracic echocardiography demonstrated an aneurysm of the left main coronary artery. On transesophageal echocardiography, the thrombus was suspected inside and severe ostial stenosis of the left coronary artery was highly suspected due to the accelerated flow velocity. Multidetector computed tomography demonstrated the aneurysm as being 37 mm in diameter with significant stenosis at both left coronary arteries, more clearly than coronary angiography. Because of its size and coexisting coronary artery disease, surgical closure of the aneurysm and coronary artery bypasses were performed. Echocardiography and coronary computed tomography could help in the diagnosis and the therapeutic decision in the case of left main coronary artery aneurysm before coronary angiography.


Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells.
Age-related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide-binding domain, leucine-rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85-90%) and wet (10-15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti-vascular endothelial growth factor (anti-VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option. Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro-oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone-induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE-19 cells). An age-related eye disease study (AREDS) formulation (incl. omega-3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone-induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance. The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). Hydroquinone induced an NLRP3-independent IL-18 release and NLRP3 accumulation inside the IL-1α-primed cells. Resvega treatment reduced the extent of hydroquinone-induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone- and impaired protein clearance-induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.


Mechanisms of prostate cancer progression to androgen independence.
Prostate cancer is a major health problem in the United States and worldwide. In 2007, more than 27,000 men were estimated to have died from prostate cancer in the United States alone. Although important advances have been made in the diagnosis and treatment of prostate cancer, therapies focused on the removal or inhibition of androgen action remain the most important components of therapy for individuals with metastatic disease. Despite the application of such modalities, the vast majority of patients with metastatic disease progress with a median survival of less than 2 years. A number of different mechanisms have been identified that may potentially contribute to the progression of prostate cancer. These insights suggest that signaling via the androgen receptor (AR) -- either via alternate signaling pathways impinging on the AR or through the in situ formation of androgens within progressive tumors -- is an important contributor to such progressive disease. It is anticipated that such mechanistic insights will lead to the development of useful new therapies in the future.


Erratum: Exploring the microbial community (microflora) associated with ovine Haemonchus contortus (macroflora) field strains.
A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Improved Glucose Intolerance through a Distinct Mouse Olfactory Receptor 23-Induced Signaling Pathway Mediating Glucose Uptake in Myotubes and Adipocytes.
It is aimed to determine the role of mouse olfactory receptor 23 (MOR23) in regulation of glucose uptake in myotubes and adipocytes and investigate whether administration of a possible MOR23 ligand, α-cedrene, attenuates the high fat diet (HFD)-induced glucose intolerance by enhancing the OR-mediated signaling pathway in mice. MOR23 is genetically inactivated by specific small interfering RNA in C2C12 myotubes and 3T3-L1 adipocytes and stimulated with α-cedrene under both basal and insulin-stimulated conditions. In addition, Male C57BL/6N mice are fed a normal diet, HFD, or HFD supplemented with 0.2% α-cedrene. In C2C12 myotubes and 3T3-L1 adipocytes, genetic inactivation of MOR23 significantly decrease glucose uptake and MOR23 downstream signaling under both basal and insulin-stimulated conditions. On the other hand, α-cedrene-mediated MOR23 stimulation results in increased glucose uptake and upregulation of MOR23 signaling molecules, absent in MOR23-depleted myotubes and adipocytes. Moreover, in mice, α-cedrene administration ameliorates HFD-induced glucose intolerance. Activation of MOR23 signaling cascade is also confirmed in basal and insulin stimulated skeletal muscles and adipose tissues of α-cedrene-treated mice. These findings suggest that MOR23 is a novel factor for the regulation of glucose uptake and whole-body glucose homeostasis and has therapeutic potential for diabetes treatment.


Cerebral and two spinal meningiomas removed from the same patient: case report.
An exceptional combination of an intracranial convexity and two thoracic spinal meningiomas in a 17-year-old girl is reported. The small meningioma in the left central parasagittal region was removed. One year later, paraplegia rapidly developed. Two meningiomas (one of them ossified) about 2 cm in size were removed from the midthoracic level of the spinal cord. The distance between the two spinal tumors was about 2 cm. One and one-half years after surgery the patient is well. The problem of multicentricity of meningiomas is discussed.


Sulfur polymer solidification/stabilization of elemental mercury waste.
Elemental mercury, contaminated with radionuclides, presents a waste disposal problem throughout the Department of Energy complex. In this paper we describe a new process to immobilize elemental mercury wastes, including those contaminated with radionuclides, in a form that is non-dispersible, will meet EPA leaching criteria, and has low mercury vapor pressure. In this stabilization and solidification process, elemental mercury is combined with an excess of powdered sulfur polymer cement (SPC) and sulfide additives in a mixing vessel and heated to approximately 40 degrees C for several hours, until all of the mercury is converted into mercuric sulfide (HgS). Additional SPC is then added and the temperature of the mixture raised to 135 degrees C, resulting in a molten liquid which is poured into a mold where it cools and solidifies. The final treated waste was characterized by powder X-ray diffraction and found to be a mixture of the hexagonal and orthorhombic forms of mercuric sulfide. The Toxicity Characteristic Leaching Procedure was used to assess mercury releases, which for the optimized process averaged 25.8 microg/l, with some samples being well below the new EPA Universal Treatment Standard of 25 microg/l. Longer term leach tests were also conducted, indicating that the leaching process was dominated by diffusion. Values for the effective diffusion coefficient averaged 7.6x10(-18) cm2/s. Concentrations of mercury vapor from treated waste in equilibrium static headspace tests averaged 0.6 mg/m3.


Prediction of protein thermostability with a direction- and distance-dependent knowledge-based potential.
The increasing use of enzymes in industrial processes and the importance of understanding protein folding and stability have led to several attempts to predict and quantify the effect of every possible amino acid exchange (mutation) on the thermostability of proteins. In this article we describe a knowledge-based discrimination function that acts as a fast and reliable guide in protein engineering and optimization. The function used consists of two parts, a pairwise energy function based on a distance- and direction-dependent atomic description of the amino acid environment, and a torsion angle energy function. In a first step a training set of 11 proteins including 646 mutant proteins with experimentally determined thermostability was used to optimize the knowledge-based energy functions. The resulting potential function was then tested using a test mutant database consisting of 918 various point mutations introduced in 27 proteins. The best correlation coefficient obtained for the experimental data and the predicted thermostability for the training set is r = 0.81 (561 data points). A total of 76% of the mutations could be predicted correctly as being either stabilizing or destabilizing. The results for the test set are r = 0.74 (747 data points) and 72%, respectively. The global correlation over the combined data (1308 mutants) obtained is 0.78.


Demonstration of acid phosphatase activity induced by 20-hydroxyecdysone in the fat body of Calliphora.
In the larval fat body of Calliphora erythrocephala, protein accumulation and autophagic activity occur prior to the onset of puparium formation. The involvement of the lysosomal system in the degradation of sequestered protein and cell organelles can be demonstrated by the electron-microscopical cytochemical localization of the lysosomal marker enzyme acid phosphatase in so-called protein granules. These granules contain not only newly synthetized or absorbed protein but also remnants of cell organelles such as mitochondria and endoplasmic reticulum. Ligation of the larvae behind the brain-ring gland complex prevents the appearance of these acid phosphatase-positive granules. They can be induced in ligated larvae by the injection of 20-hydroxyecdysone into the abdomen. These findings are briefly discussed in relation to the role of moulting hormones in normal development, especially with regard to the induction of autophagic activity.


[Anastomotic techniques in surgery of Crohn's disease-Evidence and new developments].
Intestinal anastomoses in Crohn's disease are controversially discussed. In a comparison of the different types of anastomotic configuration the side-to-side anastomosis according to Kono‑S seems to have the lowest recurrence rate. Neither the configuration of the anastomosis nor the suture material have an influence on the anastomotic leakage rate. The overall complication rate can be reduced by an amelioration of the nutritional status, a reduction of corticoids, pausing biologicals and an oral preoperative antibiotic prophylaxis.


Effect of eccentric-based rehabilitation on hand tremor intensity in Parkinson disease.
Hand tremor is a disturbing yet sometimes resistant symptom in persons with Parkinson disease (PD). Although many exercise regimens for these people have gained attention in recent years, the effect of resistance training and especially eccentric training on parkinsonian tremor is still uncertain. This study was conducted to investigate the precise effect of upper limb eccentric training on hand tremor in PD. In this randomized controlled trial, a consecutive sample of 21 persons with PD recruited from general hospitals went through 6 weeks of upper limb pure eccentric training as the intervention group (n = 11) or no additional exercise during this period as the control group (n = 10). Resting and postural tremor amplitudes were measured with the cellphone-based accelerometer. Comparing hand tremor amplitudes before and after the trial showed a significant reduction in resting tremor amplitude in the intervention group after exercise sessions (p < 0.05) while detecting no changes in the control group during 6 weeks of study. Meanwhile, postural tremor amplitude remained unchanged in both groups.


Technical Success, Sample Adequacy, and Complications of Pediatric Transjugular Liver Biopsy: A Systematic Review and Meta-Analysis.
Transjugular liver biopsy (TJLB) procedurally samples liver tissue through the internal jugular vein. It is indicated in the presence of coagulopathies and/or ascites. This meta-analysis aimed to assess the safety and efficacy of TJLB in children. A literature search of several databases was conducted from inception to August 2022. Eligible studies reported pediatric patients (< 18 years old) who underwent TJLB. The pooled proportion was analyzed using a random-effects model. This review was registered in PROSPERO (CRD42022354421). From 921 initial studies screened, eight met the eligibility criteria, with a total of 361 pediatric patients who underwent 374 TJLBs. All eight studies reported pooled rates of technical success at 99.1% (95% CI 0.982, 1.001; I2 = 0%) and histological adequacy of sampling at 97.5% (95% CI 0.954, 0.995; I2 = 27.66%). A total of 49 complications were reported across six studies, the most common being bleeding from the entry site (38.78%), fevers for less than 24 h (12.24%), red blood cells transfusion requirement (10.2%), supraventricular tachycardia (8.16%), and pain requiring analgesia (8.16%). Pediatric TJLB demonstrates high rates of technical success and adequate liver core biopsy samples, with a low rate of complications. These results suggest that TJLB is an effective method for diagnostic yield and postprocedural outcomes, especially in patients with preexisting coagulopathies and ascites where percutaneous liver biopsy is contraindicated. Additional studies evaluating larger groups of pediatric patients may provide further support for the use of TJLB in this population.


Golgi complex beads in vertebrates and their relationship with clathrin coats.
Addition of tannic acid to the primary glutaraldehyde fixative and the viewing of thin sections by stereo electron microscopy greatly simplifies the detection of vertebrate cell Golgi complex beads which are otherwise difficult to see since they do not stain with bismuth. These results confirm the generality of conclusions from experiments on arthropod beads which are easily observed because of their bismuth affinity. In vertebrate and arthropod cells, bead rings encircle the base of forming transition vesicles below the growing portion of the vesicle that is covered with a clathrin coat. Their unique position at such a sharp functional and structural boundary in intercompartmental transport suggests that the bead rings may specify a select region of rough endoplasmic reticulum devoid of ribosomes where clathrin coats can induce transition vesicle formation and prevent intermixing of the elements of a returning transition vesicle.


Fatty acid alteration in liver, brain, muscle, and oocyte of zebrafish (Danio rerio) exposed to silver nanoparticles and mitigating influence of quercetin-supplemented diet.
No to less effort has been made to assess the toxicity of silver nanoparticles (AgNPs) to lipid composition in biological systems and also to discover a mitigating agent against their oxidative stress. Hence, this research evaluated the antioxidant capability of quercetin (Qu) against silver nanoparticles (AgNPs) toxicity towards the lipid contents of ovarian, nervous, and hepatic systems as well as skeletal muscles. To this end, zebrafish (n = 180) were assigned into four experimental dietary groups: negative and positive controls, without Qu supplementation; Qu-200, 200 mg Qu per kg diet; and Qu-400, 400 mg Qu per kg diet. At the end of the feeding trial (40 days), the experimental groups, except the negative control, were exposed to sublethal concentration of AgNPs (0.15 mg L-1) for 96 h. As to the liver tissue of the positive and Qu-200 treatments, total polyunsaturated fatty acids (∑PUFA) decreased 3 times, as well as total high unsaturated fatty acids (∑HUFA) reduced about 30% and 50%, respectively. However, the brain ∑HUFA, predominated by DHA, enhanced in Qu-400 treatment. Interestingly, ∑MUFA, ∑PUFA, and ∑HUFA increased in the muscle of all treated groups, especially Qu-200 and Qu-400. The oocyte ∑MUFA content increased in the positive and Qu-200 treatments, whereas ∑HUFA reduced about 25%, 25%, and 20%, respectively, in the positive, Qu-200, and Qu-400 groups. Generally, the findings suggest that unsaturated acyl chains, particularly HUFAs, in the liver tissue and oocyte cell are highly susceptible to peroxidation or degeneration by AgNPs. More broadly, in the context of ecotoxicological risk assessment, the alteration in HUFAs and PUFAs of the liver and oocyte could impact on maternal and offspring health and consequently alter long-term population dynamics of aquatic animals.


The effect of divalent cations on the interaction between calf spleen profilin and different actins.
The interaction between calf spleen profilin and actin depends critically on the status of the C-terminus of the actin, and in the case of profilin, the C-terminus is of great importance for the physiochemical behaviour of the protein. Both proteins easily lose their C-terminal amino acids during the preparation, and special care has to be taken to ensure the isolation of the proteins in the intact form. Another factor that may seriously influence the study of the interaction of profilin with actin is the presence of varying amounts of an activity that causes an apparent stabilization of the complex even at later stages of its purification. We have found conditions for the isolation of intact profilin and actin, and studied the interaction between the two proteins, including the determination of the Kdiss for the complex formed under various ionic conditions. The complex formed between profilin and actin from calf spleen was found to be significantly stronger (Kdiss less than or equal to 10(-8) M in 50 mM KCl, and Kdiss = 4.10(-7) M in 50 mM KCl, 1 mM MgCl2) than that formed between profilin and muscle alpha-actin (Kdiss = 10(-6) M in 50 mM KCl, +/- 1 mM MgCl2). The profilactin complex formed in the mammalian system was stronger than the complex formed between Acanthamoeba actin and the profilin-like protein isolated from this organism. Analysis of the formation of the calf spleen complex in the presence of varying concentrations of divalent cations gave evidence for the presence of a high-affinity divalent-cation-binding site on the spleen actin (beta, gamma) which appears to regulate the interaction with profilin.


Osteogenic effects of covalently tethered rhBMP-2 and rhBMP-9 in an MMP-sensitive PEG hydrogel nanocomposite.
While bone morphogenic protein-2 (BMP-2) is one of the most widely studied BMPs in bone tissue engineering, BMP-9 has been purported to be a highly osteogenic BMP. This work investigates the individual osteogenic effects of recombinant human (rh) BMP-2 and rhBMP-9, when tethered into a hydrogel, on encapsulated human mesenchymal stem cells (MSCs). A matrix-metalloproteinase (MMP)-sensitive hydrogel nanocomposite, comprised of poly(ethylene glycol) crosslinked with MMP-sensitive peptides, tethered RGD, and entrapped hydroxyapatite nanoparticles was used. The rhBMPs were functionalized with free thiols and then covalently tethered into the hydrogel by a thiol-norbornene photoclick reaction. rhBMP-2 retained its full bioactivity post-thiolation, while the bioactivity of rhBMP-9 was partially reduced. Nonetheless, both rhBMPs were highly effective at enhancing osteogenesis over 12-weeks in a chemically-defined medium. Expression of ID1 and osterix, early markers of osteogenesis; collagen type I, a main component of the bone extracellular matrix (ECM); and osteopontin, bone sialoprotein II and dentin matrix protein I, mature osteoblast markers, increased with increasing concentrations of tethered rhBMP-2 or rhBMP-9. When comparing the two BMPs, rhBMP-9 led to more rapid collagen deposition and greater mineralization long-term. In summary, rhBMP-2 retained its bioactivity post-thiolation while rhBMP-9 is more susceptible to thiolation. Despite this shortcoming with rhBMP-9, both rhBMPs when tethered into this hydrogel, enhanced osteogenesis of MSCs, leading to a mature osteoblast phenotype surrounded by a mineralized ECM. STATEMENT OF SIGNIFICANCE: Osteoinductive hydrogels are a promising vehicle to deliver mesenchymal stem cells (MSCs) for bone regeneration. This study examines the in vitro osteoinductive capabilities when tethered bone morphogenic proteins (BMPs) are incorporated into a degradable biomimetic hydrogel with cell adhesive ligands, matrix metalloproteinase sensitive crosslinks for cell-mediated degradation, and hydroxyapatite nanoparticles. This study demonstrates that BMP-2 is readily thiolated and tethered without loss of bioactivity while bioactivity of BMP-9 is more susceptible to immobilization. Nonetheless, when either BMP2 or BMP9 are tethered into this hydrogel, osteogenesis of human MSCs is enhanced, bone extracellular matrix is deposited, and a mature osteoblast phenotype is achieved. This bone-biomimetic hydrogel is a promising design for stem cell-mediated bone regeneration.


Double restriction in NK cell recognition is linked to transmethylation and can be triggered by asparagine-linked oligosaccharides on tumor cells.
The determinants of tumor cell susceptibility to NK cell-mediated cytolysis were analyzed in a two stage model. The binding of tumor cells to NK effectors was measured by target-effector conjugation and cold target competition in 51Cr-release assays, whereas triggering was measured by assaying phospholipid methylation in NK cells stimulated by intact targets. Representative targets could be grouped into three phenotypes based on the data. Those such as YAC 1.2 could bind and trigger NK cells whereas the mutagenized variant, YAC 6.28.8, could bind but was unable to trigger NK cells and therefore resisted lysis. The third phenotype was represented by HL-60 which could neither bind nor trigger NK cells and was therefore completely NK resistant. The oligosaccharide nature of the triggering molecules was demonstrated by showing that purified, high mannose containing, asparagine-linked oligosaccharides from tumor cell targets were potent stimulators of NK transmethylation at submicromolar levels. Tunicamycin pretreatment of target cells inhibited their triggering capacity but not their NK binding function. These results suggest a double restriction in NK specificity involving two independent but sequential stages in recognition represented in binding and triggering by asn-linked oligosaccharides on the tumor cell surface.


Bacillus subtilis SPB1 lipopeptide biosurfactant: antibacterial efficiency against the phytopathogenic bacteria Agrobacterium tumefaciens and compared production in submerged and solid state fermentation systems.
Bacillus subtilis SPB1 derived biosurfactants (BioS) proved its bio-control activity against Agrobacterium tumefaciens using tomato plant. Almost 83% of disease symptoms triggered by Agrobacterium tumefaciens were reduced. Aiming potential application, we studied lipopeptide cost-effective production in both fermentations systems, namely the submerged fermentation (SmF) and the solid-state fermentation (SSF) as well as the use of Aleppo pine waste and confectionery effluent as cheap substrates. Optimization studies using Box-Behnken (BB) design followed by the analysis with response surface methodology were applied. When using an effluent/sea water ratio of 1, Aleppo pine waste of 14.08 g/L and an inoculum size of 0.2, a best production yield of 17.16 ± 0.91 mg/g was obtained for the SmF. While for the SSF, the best production yield of 27.59 ± 1.63 mg/g was achieved when the value of Aleppo pine waste, moisture, and inoculum size were, respectively, equal to 25 g, 75%, and 0.2. Hence, this work demonstrated the superiority of SSF over SmF.


Application of conductive polymers in biocathode of microbial fuel cells and microbial community.
Four kinds of conductive polymers, polyaniline (PANI) and its co-polymers poly (aniline-co-o-aminophenol) (PANOA), poly (aniline-co-2, 4-diaminophenol) (PANDAP) and poly (aniline-1, 8-diaminonaphthalene) (PANDAN) were applied to modify carbon felts as the aerobic abiotic cathodes and biocathodes in microbial fuel cells (MFC). Compare to unmodified, all the four polymers can significantly improve the power densities for both abiotic cathodes (increased by 300%) and biocathodes (increased by 180%). The co-polymers with different functional groups introduction had further special advantages in MFC performance: PANOA and PANDAP with -OH showed less sensitivity to DO and pH change in cathode; PANDAP and PANDAN with -NH(3) provided better attachment condition for biofilm which endowed them higher power output. With the help of conductive polymer coats, the cathode biofilm became thicker, and according to biodiversity analysis, the predominated phyla changed from β-Proteobacteria (unmodified) to α, γ-Proteobacteria (modified), which may be responsible for the superiority of the modified MFCs.


A case of solitary necrotic nodule of the liver with acute liver dysfunction: The imaging appearance correlated with pathological findings.
A 22-year-old woman was admitted to this institution because of severe liver dysfunction that looked like acute hepatitis. Abdominal ultrasonography revealed a liver mass 20 mm in diameter that resembled the bull's-eye sign. Enhanced CT revealed a low-density mass. The mass was hypointense in T1-weighted MRI images and slightly hyperintense in T2-weighted MRI images. Needle biopsy of the liver under ultrasound guidance led to a diagnosis of solitary necrotic nodule of the liver. The tumor consisted of coagulation necrosis surrounded by fibrotic tissue. These pathologic features were consistent with the Imaging findings.


Stereoselective hydrolysis of soman in human plasma and serum.
The contribution of various human serum and plasma fractions to the total hydrolysis rate constants of the four isomers of soman is studied. Spontaneous hydrolysis (as measured in buffer) occurs at a faster rate for the C(+)P(+)- and C(-)P(-)-isomers. A stereoselectively catalyzed hydrolysis of soman occurs in serum fractions IV and V (albumin). In fraction V the C(+)P(+)- and C(-)P(-)-isomers are hydrolyzed at a faster rate than their respective epimers, while in fraction IV-1 a stereoselective effect towards C(+)P(+)-soman is found. All the forementioned contributions, however, are negligible in comparison with the stereoselective enzymatic hydrolysis of the P(+)-isomers. The latter reaction is characterized by a significant lowering of the activation energy as compared with the spontaneous hydrolysis of the P(+)-isomers. Such a lowering in activation energy is not found for the hydrolysis of the P(-)-isomers in whole serum or plasma; hence it can be concluded that a phosphorylphosphatase hydrolyzes the P(+)-isomers in a stereoselective way, the P(-)-isomers either not being affected by this (these) enzyme(s) or the mechanism of catalysis being fundamentally different. This conclusion is in agreement with the observations on the influence of Hg2+ on the hydrolysis of soman in serum; the hydrolysis of the P(+)-isomers is significantly inhibited by 1 mM of Hg2+ while the P(-)-hydrolysis is unaffected by this concentration of Hg2+. The action of some potential inhibitors on this phosphorylphosphatase activity was studied. Iodoacetate did not inhibit nor did Ba2+, Sr2+, Co2+ or Mn2+ show a significant effect on the hydrolysis of the P(+)-isomers. On the other hand the hydrolytic activity in serum was nearly completely inhibited by EDTA but restored upon addition of Ca2+. These findings suggest that this enzymatic activity can be classified as an arylesterase (paraoxonase). Finally, the influence of pH on the hydrolytic activity shows a different pattern for C(+)P(+)- and C(-)P(+)-soman, which may suggest that more than one enzyme is involved in the degradation of soman.