Perceptions of unconditional and conditional worth among college students.
Self-esteem scales tend to represent conditional perceptions of self-esteem. The Worth Index has been previously validated as an effective measure for identifying both conditional and unconditional perceptions of worth. We administered the Worth Index to 1,161 college-aged students at Brigham Young University to assess their current perceptions of unconditional and conditional worth. Both men and women agreed more strongly with items involving unconditional worth than conditional worth. A negative correlation was found between ratings of unconditional and conditional worth. Women had lower unconditional worth scores than men, which was related to being more likely to wish they were someone else, desire to have a better body, and to being concerned about weight. Agreement with two overview measures of self-esteem involving a "good" sense of self and stability of self-esteem was positively associated with agreement on statements about unconditional worth. This research shows the importance of incorporating unconditional worth into self-esteem measures.


[Detection of Babes-Negri bodies in blood erythrocytes of rabid white mice].
Large numbers of polymorphous dense Babes-Negri bodies were found in brain neurons of mice sick with street rabies and dying of it. Among blood cells filling the cerebral vessels of mice dead from rabies, erythrocytes containing small dense inclusions, Babes-Negri bodies, could be seen clearly.


Influence of H7N9 virus infection and associated treatment on human gut microbiota.
Between March and June, 2013, forty H7N9 patients were hospitalized in our hospital. Next-generation sequencing technologies have been used to sequence the fecal DNA samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls. The influence of associated treatment in H7N9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technology. We found that most of the MetaGenomic Species (MGS) enriched in the control samples were Roseburia inulinivorans DSM 16841, butyrate producing bacterium SS3/4 and most of MGS enriched in the H7N9 patients were Clostridium sp. 7 2 43FAA and Enterococcus faecium. It was concluded that H7N9 viral infection and antibiotic administration have a significant effect on the microbiota community with decreased diversity and overgrowth of the bacteria such as Escherichia coli and Enterococcus faecium. Enterotype analysis showed that the communities were unstable. Treatment including antivirals, probiotics and antibiotics helps to improve the microbiota diversity and the abundance of beneficial bacteria in the gut.


Pathogenesis of pulmonary hypertension caused by left heart disease.
Pulmonary hypertension has high disability and mortality rates. Among them, pulmonary hypertension caused by left heart disease (PH-LHD) is the most common type. According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, PH-LHD is classified as group 2 pulmonary hypertension. PH-LHD belongs to postcapillary pulmonary hypertension, which is distinguished from other types of pulmonary hypertension because of its elevated pulmonary artery wedge pressure. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. The primary strategy in managing PH-LHD is optimizing treatment of the underlying cardiac disease. Recent clinical studies have found that mechanical unloading of left ventricle by an implantable non-pulsatile left ventricular assist device with continuous flow properties can reverse pulmonary hypertension in patients with heart failure. However, the specific therapies for PH in LHD have not yet been identified. Treatments that specifically target PH in LHD could slow its progression and potentially improve disease severity, leading to far better clinical outcomes. Therefore, exploring the current research on the pathogenesis of PH-LHD is important. This paper summarizes and classifies the research articles on the pathogenesis of PH-LHD to provide references for the mechanism research and clinical treatment of PH-LHD, particularly molecular targeted therapy.


[Current clinical aspects of changes in the lung parenchyma caused by the interaction of polychemotherapy and radiotherapy in the treatment of small cell bronchial cancer].
The use of radiotherapy in the treatment of bronchial carcinoma evokes changes of the healthy lung parenchyma which may lead to pneumonitis and fibrosis. At present more than 20 tumour chemotherapeutics with lung-toxical effect are known, which may induce a pneumonitis or a fibrosis. When two or more lung-toxically acting cytostatic drugs are combined, we have to take into consideration interactions with synergistic character on the healthy lung parenchyma. The combination of a lung-toxical cytostatic drug with the radiotherapy or the combination of a polychemotherapy with the radiation may cause pneumonitides and fibrosis with increased mortality rate. In our therapy programmes for the treatment of the small cell bronchial carcinoma the polychemotherapy of the tumours (I. cyclophosphamide, methotrexate, nitrosomethylurea, II. doxorubicin (adriamycin), dacarbacin, vincristine, III. cyclophosphamide, adriamycin, methotrexate) and the radiotherapy were simultaneously used. Hereby a pneumonitis was x-ray-diagnostically ascertained in more than 70% and a fibrosis in 30-80% of the patients treated. In our opinion these high rates of changes of the lung parenchyma have their cause in a complex process: interaction of the tumour chemotherapeutic drugs among one another; interaction of the tumour polychemotherapy with the radiotherapy (particularly in simultaneous application); the bronchial carcinoma is, depending upon anatomical localisation of the tumour and size a risk factor for an infection; the immunosuppressive situation of the patient increases the danger of an infection particularly in the area of the respiratory tract during the therapy. The course of a pneumonitis is decisively determined by a secondary infection.


Recent advances in amino acid analysis by capillary electromigration methods, 2013-2015.
We describe the most important research articles published on amino acid analysis using CE during the period from June 2013 to May 2015, and follows the format of the previous articles published in electrophoresis the new developments in amino acid analysis with CE are mainly describing improvements in detection means and injection methods. Enantiomeric separation developments are still important. Focusing the applications, we describe the neurochemical and clinical works, but also the metabolomic studies for which the publication number increase greatly. Finally, works focused on amino acids in food and agricultural applications are described.


Analysis of duodenal bile acids by high performance liquid chromatography in infants with cholestasis.
Non-sulfated bile acid levels including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), five taurine conjugates, and five glycine conjugates in duodenal juice were measured in 50 Chinese infants with cholestasis to test their diagnostic value. All 17 with biliary atresia (BA) cases, 11 out of 26 neonatal hepatitis (NH) cases and one case with paucity of the interlobular bile duct were without detectable bile acids. In those NH patients with detectable bile acids, the major components were conjugated forms of CA and CDCA, which was similar to all 6 cases of the comparison group with other diseases. The minor bile acid components identified in them were glycine conjugated UDCA, free CDCA, free CA, and free and conjugated DCA. Only one patient with NH had taurine conjugated LCA. The mean total duodenal bile acid level in 15 patients with NH was significantly lower than that in the 6 patients of the comparison group. Most patients with NH had a CDCA/CA ratio of less than one, indicating that cholic acid is the predominant form in their bile. Glycine conjugated bile acids were the predominant bile acids present in 11 out of 15 patients with NH and 4 out of 6 of the comparison group patients. The results suggest that the detection of duodenal bile acids by a sensitive HPLC method is of limited value in making a differential diagnosis between BA and NH.(ABSTRACT TRUNCATED AT 250 WORDS)


Scirrhous argyrophil cell carcinoma of the stomach with multiple production of polypeptide hormones, amine, CEA, lysozyme, and HCG.
Sixteen argyrophil cell carcinomas in 59 gastric scirrhous carcinomas were examined histologically, ultrastructurally, and immunohistochemically for polypeptide hormones, CEA, lysozyme, and HCG. In nine of these 16 tumors, polypeptides such as gastrin, somatostatin, and glucagon were demonstrated. Six of these nine tumors contained all three hormones, and three of these six tumors also had argentaffin cells. In all of these 16 tumors CEA were observed. Eight of them had CEA, lysozyme, and acid mucin synchronously. Of the above six tumors containing three peptides, three produced focal HCG. Ultrastructurally, several types of secretory granules were noted. Histologically, these 16 tumors showed poorly differentiated adenocarcinomas or signet ring cell carcinomas. Macroscopically, generalized type was 11 and localized type five. No hormonal syndrome was detected in any of the patients. It was suggested that these scirrhous argyrophil cell carcinomas of the stomach with the multifunction originate from totipotent immature cells of endodermal origin.


A Comparative Study between the Postoperative Complications of Stripping Esophagectomy and Classic (Orringer's Technique) Esophagectomy.
Recent studies have suggested that morbidity and mortality rate of transhiatal esophagectomy is comparable to that of thoracotomy, calling the need for the modifications in the surgical procedures. Our methodology includes stripping of esophagus by nasogastric tube to reduce the manipulation of thoracic cavity and associated complications. We also present the comparison between the stripping and classic (Orringer's technique) esophagectomy. Patients presenting esophageal carcinoma from 2015 to 2017 were the target of this study. Patients undergoing esophagectomy were randomized to have classic or stripping esophagectomy. Operating time, manipulation time, blood losses during the surgery, duration of hospitalization, volume intake, hypotension time, arrhythmia, and transfusion were the recorded parameters. Complications, such as anastomotic leak, cardiac effects, and morbidity, were also studied. Seventy patients were referred for transhiatal esophagectomy for esophageal carcinoma at the Al Zahra Hospital. Mean ages of patients in the stripping and Orringer group were 64.00 ± 10.57 and 57.42 ± 12.20 years, respectively. Manipulation time, operating time, blood loss during the surgery, and transfusion were statistically significant variables between the two groups. Although volume intake and duration of hospitalization were not significantly different parameters, however, betterment in the outcomes was evident. Substantial decrease in overall complications via stripping method was obtained, hence can be suggested as an effective alternative, to remove the need of thoracotomy, for transhiatal esophagectomy.


A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.


Characterization of biofilms in biliary stents and potential factors involved in occlusion.
To quantify the components in biofilms and analyze the predisposing factors involved in occlusion of biliary stents. In a prospective study conducted from April 2011 to March 2014 at a tertiary care hospital, all consecutive patients who required endoscopic biliary stent exchange/removal were included. Etiology of the biliary disease was diagnosed by imaging, cytology and on follow-up. Clinical details of patients with biliary stent retrieval were noted. All extracted stents were collected in sterile containers and immediately processed for quantification of biofilm proteins and polysaccharides. Molecular identification of commonly known and unknown bacteria was performed by polymerase chain reaction and density gradient gel electrophoresis methods. Eighty one patients (41 males) with age range of 20-86 years were studied. The underlying causes for stent insertion were bile duct stones (n = 46; 56.8%) benign stricture (n = 29; 35.8%) and malignancy (n = 6; 7.4%) with cholangitis in 50 (61.7%) patients. The retrieved stent sizes were 7 Fr (n = 62; 76.5%) and 10 Fr (n = 19; 23.5%) with 65 days median insertion duration. Polybacterial consortia were detected in 90.1% of the stents. The most common bacteria identified by polymerase chain reaction alone and/or sequencing were Pseudomonas (n = 38), Citrobacter (n = 23), Klebsiella (n = 22), Staphylococcus (n = 20), Serratia (n = 16), Escherichia coli (n = 14), Streptococcus (n = 13), Enterococcus (n = 13), Aeromonas (n = 12), Proteus (n = 10) and Enterobacter (n = 9). Protein concentration according to gender (0.547 ± 0.242 mg/mL vs 0.458 ± 0.259 mg/mL; P = 0.115) as well as age > 60 years and < 60 years (0.468 ± 0.295 mg/mL vs 0.386 ± 0.238 mg/mL; P = 0.205) was non-significant. However, polysaccharide concentration was significant both according to gender (0.052 ± 0.021 mg/mL vs 0.049 ± 0.016 mg/mL; P < 0.0001) and age (0.051 ± 0.026 mg/mL vs 0.038 ± 0.016 mg/mL; P < 0.011). Protein concentration in the biofilm was significantly higher (0.555 ± 0.225 mg/mL vs 0.419 ± 0.276 mg/mL; P = 0.018) in patients with cholangitis, lower (0.356 ± 0.252 mg/mL vs 0.541 ± 0.238 mg/mL; P = 0.005) in the 10 Fr group than the 7 Fr group, and significantly higher (0.609 ± 0.240 mg/mL vs 0.476 ± 0.251 mg/mL; P = 0.060) in stents of ≥ 6 mo of indwelling time. However presence/absence of cholangitis, size of stent, indication of stent insertion and indwelling time did not affect the quantity of polysaccharide concentration. Plastic stents retrieved from patients with biliary tract disease showed polymicrobial organisms with higher protein content among patients with cholangitis and those with smaller diameter stents. Longer indwelling duration had more biofilm formation.


Affective disorders and ABO blood groups: new data and a reanalysis of the literature using the logistic transformation of proportions.
No statistically significant associations were found between ABO blood group distributions and RDC subtype diagnoses in 79 subjects with unipolar (single episode and recurrent) and bipolar major depressive disorder using data from our sample. We discuss methodological issues related to the control samples and choice of statistical methods in the reported studies which have looked for associations between ABO blood types and patients diagnosed as having an affective disorder. After presenting our rationale for employing the logarithm of the cross product ratio (lambda) in place of the more traditionally utilized chi-squared, we used lambda to reanalyze the original data from nine studies in the literature. The individual studies are equivocal on the basic issue of an association between type O blood and bipolar I illness, either compared to controls or to recurrent unipolar patients. The combined (weighted average) measure of association indicates a small but definite association, but statistical analysis of the dispersion of the individual estimates around this combined estimate reveals that the studies have a higher degree of heterogeneity in results than expected by chance. The consequences of this finding are discussed, and possible explanations are offered.


Computational model of cytokinetic abscission driven by ESCRT-III polymerization and remodeling.
The endosomal sorting complex required for transport (ESCRT)-III complex, capable of polymerization and remodeling, participates in abscission of the intercellular membrane bridge connecting two daughter cells at the end of cytokinesis. Here, we integrate quantitative imaging of ESCRT-III during cytokinetic abscission with biophysical properties of ESCRT-III complexes to formulate and test a computational model for ESCRT-mediated cytokinetic abscission. We propose that cytokinetic abscission is driven by an ESCRT-III fission complex, which arises from ESCRT-III polymerization at the edge of the cytokinetic midbody structure, located at the center of the intercellular bridge. Formation of the fission complex is completed by remodeling and breakage of the ESCRT-III polymer assisted by VPS4. Subsequent spontaneous constriction of the fission complex generates bending deformation of the intercellular bridge membrane. The related membrane elastic force propels the fission complex along the intercellular bridge away from the midbody until it reaches an equilibrium position, determining the scission site. Membrane attachment to the dome-like end-cap of the fission complex drives membrane fission, completing the abscission process. We substantiate the model by theoretical analysis of the membrane elastic energy and by experimental verification of the major model assumptions.


Screening, identification, purification and homologous modeling of marine cold-active alpha-amylase.
Cold-active α-amylase is essential in industrial production. However, the number of cold-active α-amylases available for use is limited. Screening microbial strains would lay the groundwork for the future development of the food and pharmaceutical industries. To screen microbial strains for cold-active α-amylase based on physiological and biochemical identification, as well as homology modelling. Cold-active α-amylase strains were screened from water and mud obtained from the Yellow Sea. Colony morphology, Gram staining, scanning electron microscopy and transmission electron microscopy, physiological and biochemical identification and 16S rRNA gene analysis were used to identify strains. A series of steps, including DEAE-anion exchange column chromatography, SephadexG-100 column chromatography, and SDS-PAGE electrophoresis, were used to produce cold-active α-amylase of relatively high purity. Finally, the homology of amylase was modeled to explore the structure and activity site of the enzyme. The named dsh19-1 strain of cold-active α-amylase was screened and identified as Bacillus. The cold-active α-amylase produced by Bacillus was named AmyD-1. The protein with PDB sequence number 5A2B was found to have 40.6% homology with AmyD-1. The verification score of the 3-D model was 137.07 points. We discovered that the six sites are potential sites for amylase to decompose starch by building a 3-D AmyD-1 model. AmyD-1 has a molecular weight of 1515 bp, and hydrogen bonding may be the primary interaction force between AmyD-1 and glucose molecules. A cold-active α-amylase produced by Bacillus strain dsh19-1 was successfully obtained and named AmyD-1. This enzyme has potential uses in the food and pharmaceutical industries.


Inferring microbial interactions in thermophilic and mesophilic anaerobic digestion of hog waste.
Anaerobic digestion (AnD) is a microbiological process that converts organic waste materials into biogas. Because of its high methane content, biogas is a combustible energy source and serves as an important environmental technology commonly used in the management of animal waste generated on large animal farms. Much work has been done on hardware design and process engineering for the generation of biogas. However, little is known about the complexity of the microbiology in this process. In particular, how microbes interact in the digester and eventually breakdown and convert organic matter into biogas is still regarded as a "black box." We used 16S rRNA sequencing as a tool to study the microbial community in laboratory hog waste digesters under tightly controlled conditions, and systematically unraveled the distinct interaction networks of two microbial communities from mesophilic (MAnD) and thermophilic anaerobic digestion (TAnD). Under thermophilic conditions, the well-known association between hydrogen-producing bacteria, e.g., Ruminococcaceae and Prevotellaceae, and hydrotrophic methanogens, Methanomicrobiaceae, was reverse engineered by their interactive topological niches. The inferred interaction network provides a sketch enabling the determination of microbial interactive relationships that conventional strategy of finding differential taxa was hard to achieve. This research is still in its infancy, but it can help to depict the dynamics of microbial ecosystems and to lay the groundwork for understanding how microorganisms cohabit in the anaerobic digester.


Design, Preparation and Characterization of Modular Squalene-based Nanosystems for Controlled Drug Release.
This article reviews the innovative and original concept the "squalenoylation", a technology allowing the formulation of a wide range of drug molecules (both hydrophilic and lipophilic) as nanoparticles. The "squalenoylation" approach is based on the covalent linkage between the squalene, a natural and biocompatible lipid belonging to the terpenoid family, and a drug, in order to increase its pharmacological efficacy. Fundamentally, the dynamically folded conformation of squalene triggers the resulting squalene-drug bioconjugates to self-assemble as nanoparticles of 100-300 nm. In general, these nanoparticles showed long blood circulation times after intravenous administration and improved pharmacological activity with reduced side effects and toxicity. This flexible and generic technique opens exciting perspectives in the drug delivery field.


Hepatitis B Virus-Related Glomerulonephritis with Positive and Negative Serum HBsAg: Different Clinicopathologic Characteristics of Two Clinical Subtypes.
The clinicopathologic characteristics of Hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with different serum HBsAg are not well known. This study aims to investigate the characteristics and treatments between HBV-GN patients with positive and negative serum HBsAg. A retrospective review of patients with renal biopsies in Guangdong Provincial People's Hospital from 2005 to 2018 was performed. Clinicopathological data, treatments and remission of proteinuria were collected and compared between HBsAg+ and HBsAg- group. A total of 101 HBV-GN were recruited. Serum HBsAg+ and HBsAg- patients accounted for 62.4% and 37.6%, respectively. HBsAg+ group had poor kidney and liver functions. Pathological data showed the percentage of membranous nephropathy in HBsAg- group is significantly higher than that of HBsAg+ group (60.3% HBsAg+ vs 89.5% HBsAg-, P<0.05). Chronic renal tubular/interstitial injury was more prevalent in HBsAg+ group (16.9% HBsAg+ vs 2.6% HBsAg-, P<0.05). The deposition sites of immune complexes were significant different between the two groups. In addition, more HBsAg+ patients were given anti-HBV and less were given corticosteroid or immunosuppressants for treatment than that of HBsAg- patients. Percentages of clinical remission were increasing in both HBsAg+ and HBsAg- patients from 1, 3, 6 months to 1 year (18.75%, 45.2%, 67.8%, 82.4% vs 24.4%, 41.2%, 62.8%, 59.3%). The differences of remission betwen two groups were not significant (P>0.05). The clinicopathological characteristics and treatments of HBV-GN with serum HBsAg+ and HBsAg- were distinct, which indicated that the pathogenesis might be different and specific treatments were needed for HBV-GN patients with different serum HBsAg.


Pharmacoeconomic evaluations in the treatment of actinic keratoses.
Actinic keratoses (AKs) develop as a consequence of chronic ultraviolet (UV) exposure and exist on a continuum with squamous cell carcinoma (SCC). As one of the most common conditions treated by dermatologists, AK places a significant burden on patients and the healthcare system. A range of treatments are used, including topical treatments that target the visible and subclinical lesions. The goal of such therapies is to achieve complete clearance of AKs and eliminate the risk of progression to SCC. Robust meta-analyses of trial data can provide valuable information for the optimal management of AK and cost-effectiveness evaluations of topical treatments, such as ingenol mebutate gel and diclofenac. These outcomes can facilitate prescribing physicians' decisions and shape therapeutic guidelines. Peer-reviewed meta-analysis publications and treatment guidelines favoured ingenol mebutate efficacy over diclofenac and the relative cost-effectiveness of ingenol mebutate. We discuss and critique recent evidence, from a cost-effectiveness analysis of 3% diclofenac sodium and ingenol mebutate in the treatment of AK in Italy, which has challenged this view.


Preparing transition-metal clusters in known structural forms: the mass-analyzed threshold ionization spectrum of V3.
The first results are presented of a new experiment designed both to generate and characterize spectroscopically individual isomers of transition-metal cluster cations. As a proof of concept the one-photon mass-analyzed threshold ionization (MATI) spectrum of V3 has been recorded in the region of 44,000-45,000 cm-1. This study extends the range of a previous zero-kinetic-energy (ZEKE) photoelectron study of Yang et al. [Chem. Phys. Lett. 231, 177 (1994)] with which the current results are compared. The MATI spectra reported here exhibit surprisingly high resolution (0.2 cm-1) for this technique despite the use of large discrimination and extraction fields. Analysis of the rotational profile of the origin band allows assignment of the V3 ground state as and the V3+ ground state as , both with D3h geometry, in agreement with the density-functional theory study of the V3 ZEKE spectrum by Calaminici et al. [J. Chem. Phys. 114, 4036 (2001)]. There is also some evidence in the spectrum of transitions to the low-lying excited state of the ion. The vibrational structure observed in the MATI spectrum is, however, significantly different to and less extensive than that predicted in the density-functional theory study. Possible reasons for the discrepancies are discussed and an alternative assignment is proposed which results in revised values for the vibrational wave numbers of both the neutral and ionic states. These studies demonstrate the efficient generation of cluster ions in known structural (isomeric) forms and pave the way for the study of cluster reactivity as a function of geometrical structure.


The Risk of Gynecologic and Urinary Tract Cancer with Pelvic Inflammatory Disease: A Population-Based Cohort Study.
Purpose: The aim of the study was to determine the association between pelvic inflammatory disease (PID) and breast, colorectal, gynecologic and urinary tract cancer. Methods: The source of data was a longitudinal dataset compiled by the Longitudinal Health Insurance Database 2000 (LHID2000) which was collected by the National Health Insurance program. Cases of PID, at least two outpatient visits and one admission, were diagnosed from 2000 to 2013. The data for controls, age matched women who were not diagnosed with PID from 2000 to 2013, were also obtained. Results: A total of 47,333 PID cases and 189,332 for control group were included in the study. The ectopic pregnancy incidence rate (per 10000 person months) was 1.912 and 0.595 in the PID and control group, respectively; the rate ratio was 3.211 (confidence interval, CI = 2.931-3.519). There were significantly different in gynecologic cancers and urinary tract cancers between the PID and control group; the rate ratios (95% C.I.) were 1.903 (1.672-2.166) and 1.566 (1.211-2.025), respectively. Conclusion: Our study found that PID was associated with increased risks of gynecologic and urinary tract cancer but not colorectal or breast cancer. The information may lead to a strategy for cancer prevention and a reasonable healthcare usage through understanding PID epidemiology and controlling the inflammatory responses.


Addressing suicide risk in partners and relatives bereaved by suicide.
Analyses of population-based registers provide evidence to support an increased risk of suicide and mental illness after the suicide of a relative or partner. This editorial explores the implications of this work for progressing recommendations made in suicide prevention strategies regarding the specific support provided to people bereaved by suicide. Declaration of interest A.P. served on the Public Health England expert reference committee contributing to local guidance on commissioning and delivering postvention support (Public Health England, 2016. Support After a Suicide: A Guide to Providing Local Services) and has submitted applications for funding to investigate mediators of suicide risk after suicide bereavement. Since writing this article she has become a Patron of the Support After Suicide Partnership.


Effects of porcine secretin on exocrine and endocrine function in the isolated perfused rat pancreas.
The effects of both synthetic and pure natural porcine secretin on immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) release and on pancreatic exocrine secretion were studied in the isolated perfused rat pancreas. Synthetic porcine secretin stimulated a significant increase in pancreatic juice flow and amylase output at concentrations as low as 0.01 and 0.1 ng/ml, respectively. The maximal peak rate of both juice flow and amylase output was observed at 1 microgram/ml synthetic secretin. Synthetic secretin at concentrations up to 2 micrograms/ml and pure natural porcine secretin at a concentration of 1 clinical unit/ml had no effect on IRI secretion regardless of the glucose concentration (50, 100, or 150 mg/100 ml) in the perfusate. Both types of secretin, however, elicited a concentration-dependent increase in IRG secretion in the presence of 50 mg/100 ml glucose. The lowest synthetic secretin concentration causing a significant increase in IRG release was 0.1 ng/ml, and maximal stimulation was observed at 1 microgram/ml. These concentrations were similar to those eliciting minimal and maximal amylase release. Thus, synthetic and pure natural porcine secretin have been shown to not only stimulate pancreatic juice flow and amylase secretion but also to elicit IRG release from the isolated perfused rat pancreas.


Determinants of Low Birth Weight among Newborns Delivered at Public Hospitals in Sidama Zone, South Ethiopia: Unmatched Case-Control Study.
Low birth weight is a global public health problem having various severe and life-threatening health effects. The World Health Organization is working to reduce the prevalence of low birth weight to 30% by the year 2025. Pinpointing the determinants of low birth weight at different scenarios is crucial to reduce the rate of low birth weight in low-income countries which consist of 96.5% of global low birth weight newborns. Thus, the aim of this study was to assess determinants of low birth weight in Sidama Zone public hospitals of South Ethiopia. An institution-based case-control study was conducted from March 1 to May 5, 2019, in Sidama Zone public hospitals. Data were collected from 354 mother-neonate samples with 118 of them having newborns with birth weight < 2500 g (cases) and 236 of them having birth weight ≥ 2500 g (controls) using a pretested, interviewer-administered structured questionnaire and medical record review. The odds of being rural dweller women was 3.51 times higher among cases (low birth weight babies) than among controls (normal birth weight babies) as compared to being urban dweller women (AOR = 3.51, 95% CI (1.91-6.45)). The likelihood of initiating antenatal care late was 3.22 times more among cases than among controls when compared with timely initiation of antenatal care (AOR = 3.22, 95% CI (1.47-7.14)). The probability of having pregnancy-induced hypertension was 4.49 times higher among mothers of the cases than among mothers of the controls as compared to not having pregnancy-induced hypertension (AOR = 4.49, 95% CI (1.94-10.38)). The odds of not taking iron and folic acid during pregnancy was 3.92 times higher among mothers of the cases than mothers of the controls when compared with taking iron and folic acid (AOR = 3.92, 95% CI (1.80-8.50)). The likelihood of having Mid-Upper Arm Circumference (MUAC) < 23 cm was 4.27 times higher among mothers of the cases than among mothers of the controls as compared to having MUAC ≥ 23 cm (AOR = 4.27, 95% CI (2.24-8.12)). The probability of having inadequate dietary diversity was 3.75 times higher among cases than among controls as compared to having adequate dietary diversity (AOR = 3.75, 95% CI (1.64-8.57)). Interventions targeting the aversion of low birth weight should focus on promotion of iron-folic acid supplementation and dietary diversification through timely initiation of antenatal care.


Diagnosis of ischemic heart disease with exercise echocardiography: Comparison of images obtained at peak- and post-exercise.
Peak-and post-exercise stress echocardiography were compared with respect to ability to detect coronary artery disease in 138 consecutive patients undergoing supine bicycle stress echocardiography. Sixty of these patients had single-vessel disease; 37, double-vessel disease; and 19, triple-vessel disease. Exercise was performed in the 20- to 30-degree left decubitus position on an echo-bed with an ergometer. Exercise started at 50 watts and was increased in 25-watt every 3 minutes and to a maximum of 150 watts. Two-dimensional echocardiographic images were digitized and assigned in a quad-screen format for nonbiased interpretation. Total wall motion score (TWMS) was the sum of the wall motion score, from normokinesis (0) to dyskinesis (4), of 16 segments. Image quality score index (IQSI) was the mean of the image quality scores in all views. All of the patients underwent coronary arteriography. Significant coronary stenosis was defined as≧75% stenosis of the large coronary arteries. Two-dimensional echocardiographic studies were adequate for analysis in 133 patients during the peak-exercise stage (peak-exercise) and in 137 patients 30 to 60 seconds after the end of exercise (post-exercise). TWMS at peak-exercise was higher than at post-exercise, while IQSI at peak-exercise was lower than at post-exercise. Sensitivity at peak-exercise versus that at post-exercise was 91% versus 79% (p<0.05); specificity, 76% versus 85%; and diagnostic accuracy, 88% versus 80% (p<0.05), respectively. We conclude that despite poor image quality on exercise echocardiography, better diagnostic accuracy was attained by assessing wall motion changes at peak-exercise than at post-exercise.


A study of thyroglobulin concentration in the thyroid and serum of patients with different thyroid disorders.
Knowledge concerning the structure and quality of thyroglobulin (Tg) has great significance for the better understanding of the pathogenesis of different thyroid diseases. The localization of the Tg gene and studies of its structure by molecular biological techniques make possible precise investigations of its expression. The aim of our study was to evaluate Tg content in the thyroids and Tg concentrations in the serum of 108 patients suffering from benign or malignant thyroid disorders. The method of investigation was isolating total protein from thyroid tissues obtained during surgery and determining Tg content in the thyroid extracts and Tg concentrations in serum. The Tg concentrations in serum and in thyroid protein extracts were evaluated by fluoroimmunometric assay. Statistical analysis was carried out with the help of the computing programmes.


Phosphorylation by protein kinase a inhibits nuclear import of 5-lipoxygenase.
The enzyme 5-lipoxygenase initiates the synthesis of leukotrienes from arachidonic acid. Protein kinase A phosphorylates 5-lipoxygenase on Ser(523), and this reduces its activity. We report here that phosphorylation of Ser(523) also shifts the subcellular distribution of 5-lipoxygenase from the nucleus to the cytoplasm. Phosphorylation and redistribution of 5-lipoxygenase could be produced by overexpression of the protein kinase A catalytic subunit alpha, by pharmacological activators of protein kinase A, and by prostaglandin E(2). Mimicking phosphorylation by replacing Ser(523) with glutamic acid caused cytoplasmic localization; replacement of Ser(523) with alanine prevented phosphorylation and redistribution in response to protein kinase A activation. Because Ser(523) is positioned within the nuclear localization sequence-518 of 5-lipoxygenase, the ability of protein kinase A to phosphorylate and alter the localization of green fluorescent protein fused to the nuclear localization sequence-518 peptide was also tested. Site-directed replacement of Ser(523) with glutamic acid within the peptide impaired nuclear accumulation; overexpression of the protein kinase A catalytic subunit alpha and pharmacological activation of protein kinase caused phosphorylation of the fusion protein at Ser(523), and the phosphorylated protein was found chiefly in the cytoplasm. Taken together, these results indicate that phosphorylation of Ser(523) inhibits the nuclear import function of a nuclear localization sequence, resulting in the accumulation of 5-lipoxygenase enzyme in the cytoplasm. As cytoplasmic localization can be associated with reduced leukotriene synthetic capacity, phosphorylation of Ser(523) serves to inhibit leukotriene production by both impairing catalytic activity and by placing the enzyme in a site that is unfavorable for action.


Clinical Aspects of Drug-Drug Interaction and Drug Nephrotoxicity at Renal Organic Cation Transporters 2 (OCT2) and Multidrug and Toxin Exclusion 1, and 2-K (MATE1/MATE2-K).
The organic cation transporter 2 (OCT2) belongs to the SLC22 family, while the multidrug and toxin extrusion 1 and 2-K (MATE1/MATE2-K) belong to the SLC47 family, are localized to the basolateral and apical membrane of human renal proximal tubular epithelial cells, respectively. They are polyspecific transporters that enable the transit of structurally diversified drugs with overlapping selectivity across plasma membranes. OCT2 and MATE1/2-K are critically involved in renal secretion, pharmacokinetics (PK), and toxicity of cationic drugs. Drug-drug interactions (DDIs) at OCT2 and/or MATE1/2-K have been shown to result in clinical impacts on PK, therapeutic efficacy and are probably involved in the renal accumulation of drugs. Sites of OCT2 and MATE1/2-K expression and function play an essential role in the pharmacokinetics and toxicity of drugs, such as cisplatin. Thus, knowing the sites (basolateral vs. apical) of the interaction of two drugs at transporters is essential to understanding whether this interaction helps prevent or enhance drug-induced nephrotoxicity. In this work, an overview of OCT2 and MATE1/2-K is presented. Primary structure, membrane location, functional properties, and clinical impact of OCT2 and MATE1/2-K are presented. In addition, clinical aspects of DDIs in OCT2 and MATE1/2-K and their involvement in drug nephrotoxicity are compiled.


Characterization of textured NiO films for application as buffer layers in high temperature superconducting tapes.
Textured NiO films have been grown, by thermal oxidation, on biaxially textured Ni substrates. The films have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The XRD results showed two texture components, cube texture (001)[100] and (111) with out of plane orientation only. SEM showed much inhomogeneity of grain size on the sample surface. Analysis by EBSD revealed that coarse grained regions were cube textured and fine grained regions were <111> fibre textured. The ability to correlate textural and microstructural data is crucial to the optimization of textured NiO films for use in coated conductor technology.


Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model.
Fu's subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal's body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat's discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.


Getting Into Urgent Care.
Many primary care physicians opt to open "urgent care" facilities or add urgent care services to their practices. Although there are advantages - such as billing and appointment scheduling flexibility - there are headaches as well.


Dechlorinated Ullmann Coupling Reaction of Aryl Chlorides on Ag(111): A Combined STM and XPS Study.
Surface-assisted Ullmann coupling was widely applied to construct various molecular nanostructures on surfaces due to its reliability and controllability. By using 4,4''-dichloro-1,1':3',1''-terphenyl (DCTP) as the precursor, covalently bonded zig-zag oligophenylene chains and hexagonal hyperbenzene rings, e. g., [18]-honeycombenes, were successfully fabricated on Ag(111) via dechlorinated Ullmann coupling reaction. Stepwise annealing was applied to investigate the reaction process in detail. Scanning tunneling microscopy and synchrotron X-ray photoemission spectroscopy were utilized to explore the thermal evolution of the DCTP molecules on Ag(111) under ultrahigh vacuum conditions, evidencing the existence of intact DCTP molecules, chemisorbed Cl atoms, covalently bonded DCTP dimers as well as organometallic C-Ag-C-containing intermediates. These results may help understand dechlorinated Ullmann coupling reaction of aryl chlorides on metal surfaces.


[Estimation of glomerular filtration rate in primary care: prevalence of chronic kidney disease and impact on referral to nephrology].
Data were collected in 18.922 patients attending Primary Care Centers in Alcañiz (Spain), mean age 59,96 +/- 17 years, 42,9 % males and 57,1 % females. The prevalence of eGFR was: stage 3 (30-59 ml/min/1,73 m2) 15,7 %; stage 4 (15-29 ml/min/1,73 m2) 0,6 %; stage 5 no dialysis (GFR < 15 ml/min/1.73 m2) 0,1 %. This prevalence increased with age and 32 % of patients attending Primary Care services over 65 years presented a eGFR < 60 ml/min/1,73 m2. Of the total patients with eGFR < 60 ml/min/1,73 m2, 26 % had normal serum creatinine levels. Protocol implementation could implied for the Renal Unit an increase in the number of patients, specially the oldest ones. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level and the importance of Primary Care collaboration in their early identification and appropriate management.


Elevated levels of antibodies to polyuridylic acid detected and quantitated in systemic scleroderma patients by solid phase radioimmunoassay.
A solid support radioimmunoassay has been developed to detect immunoglobulin specific circulating antibodies to polyuridylic acid (Pol U), single-stranded RNA (ss RNA), and single-stranded DNA (ss DNA) in scleroderma and other connective tissue diseases. The assay system uses flex-vinyl microtiter plates on which bovine methyl albumin, the respective polynucleotide, a 1:80 dilution of patient serum, and tritiated high affinity anti-IgG, -IgA, or -IgM are layered. The individual wells containing the sandwich assay are then counted for the presence of labeled immunoglobulins and the results are reported in microgram/ml. Of the 30 scleroderma patients tested, only patients with diffuse systemic scleroderma had antibody levels reactive to Poly U > 4.0 microgram/ml and to ss RNA < 3.0 microgram/ml. Patients with linear scleroderma or morphea had antibody levels to Poly U < 3.0 microgram/ml and very little antibody to ss DNA or ss RNA in their sera. Partial cross reactivity to Poly U was found only in SLE patients with high levels of Ab to ss DNA. Insignificant levels of Poly U antibody were found in patients with other connective tissue diseases and in normal controls. High levels of serum antibody in patients which reacted with Poly U suggest active diffuse systemic scleroderma.


[Zinc induces normoxic accumulation of transcriptionally active hypoxia-inducible factor 1-alpha in mammary epithelial cells].
Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A mammary epithelial cell lines, the toxicity levels of zinc differ. Interestingly, both cell lines overexpress HIF-1α following zinc treatment. As it was evident from an up-regulation of its specific target gene CA9 that encodes carbonic anhydrase IX, the stabilized HIF-1α translocated to the nucleus and was transcriptionally active. Hence, we conclude that zinc causes normoxic accumulation of transcriptionally active HIF-1α by interfering with its post-translational regulation.


Alcohol abuse and suicidal behaviour.
The Psychiatric emergency clinic (PEC) was established at University Psychiatric Hospital Ljubljana in 2004. 2760 patients were examined in the PEC until the end of May 2004. We have gathered data from medical documentation about the patient's age, suicidal behaviour, pharmacotherapy and psychoactive substances misuse. We compared patients with substance misuse and patients without substance misuse regarding suicidal behaviour and prescribed psychopharmacotherapy. There was a significant difference in suicidal behaviour between the group of those, who abused PAS (n=497) and those who did not (35.4% vs. 28.0%, N = 1753, Pearson Chi-Square Test, p<0.001). More patients who abused PAS attempted suicide (9.5% vs. 3.5%, N = 2760, Fisher's Exact Test, p < 0.001). However, we have not observed a difference between the groups regarding suicidal threats and thoughts (17.2% vs. 18.0%, N = 2592, Fisher's exact test, p = NS). The subgroup of patients with PAS abuse have been prescribed pharmacotherapy more often than others (19.4% vs. 11.4%, N = 2592, Fisher's Exact Test, p < 0.001). Our data is in accordance with previous observations that PAS abuse is a risk factor for suicidal behaviour.


Bacterial fucose-rich polysaccharide stabilizes MAPK-mediated Nrf2/Keap1 signaling by directly scavenging reactive oxygen species during hydrogen peroxide-induced apoptosis of human lung fibroblast cells.
Continuous free radical assault upsets cellular homeostasis and dysregulates associated signaling pathways to promote stress-induced cell death. In spite of the continuous development and implementation of effective therapeutic strategies, limitations in treatments for stress-induced toxicities remain. The purpose of the present study was to determine the potential therapeutic efficacy of bacterial fucose polysaccharides against hydrogen peroxide (H2O2)-induced stress in human lung fibroblast (WI38) cells and to understand the associated molecular mechanisms. In two different fermentation processes, Bacillus megaterium RB-05 biosynthesized two non-identical fucose polysaccharides; of these, the polysaccharide having a high-fucose content (∼ 42%) conferred the maximum free radical scavenging efficiency in vitro. Structural characterizations of the purified polysaccharides were performed using HPLC, GC-MS, and (1)H/(13)C/2D-COSY NMR. H2O2 (300 µM) insult to WI38 cells showed anti-proliferative effects by inducing intracellular reactive oxygen species (ROS) and by disrupting mitochondrial membrane permeability, followed by apoptosis. The polysaccharide (250 µg/mL) attenuated the cell death process by directly scavenging intracellular ROS rather than activating endogenous antioxidant enzymes. This process encompasses inhibition of caspase-9/3/7, a decrease in the ratio of Bax/Bcl2, relocalization of translocated Bax and cytochrome c, upregulation of anti-apoptotic members of the Bcl2 family and a decrease in the phosphorylation of MAPKs (mitogen activated protein kinases). Furthermore, cellular homeostasis was re-established via stabilization of MAPK-mediated Nrf2/Keap1 signaling and transcription of downstream cytoprotective genes. This molecular study uniquely introduces a fucose-rich bacterial polysaccharide as a potential inhibitor of H2O2-induced stress and toxicities.


Involvement of small leucine-rich proteoglycans and telocytes in thin and thick human endometrium: immunohistochemical and ultrastructural examination.
Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium (p < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium (p < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium.


Polymorphic organization of the endoplasmic reticulum of the Malpighian tubule. Evidence for a transcellular route.
Isosmotic fluid absorption carried out by many mammalian epithelia appears to be similar to the isosmotic secretion of insect epithelia such as the Malpighian tubules, which are responsible for urine formation and osmoregulation. We have studied by electron microscopy (80 kV) the three-dimensional characteristics of organelles in the Malpighian tubules of Rhodnius prolixus using thick sections (0.3-0.5 microns) and uranyl and lead impregnation. The ER presents a different organization in the upper (distal) and lower (proximal) segments of the Malpighian tubule. In distal secretory segment, the ER forms a network made of chains of vesicles having irregular shapes (ca. 0.06 micron in diameter) connected to each other by canaliculi while in the lower absorptive segment, the ER is made of parallel saccules arranged in stacks or whorls in the central region of the cytoplasm. In both segments, the ER network extends throughout the cytoplasm from the basolateral infoldings to the apex between the many mitochondria present in these two areas. A unique feature of these cells, revealed by thick sections, is the presence in each microvillus of either a mitochondrion or an ER canaliculus in continuity with the ER network. The ER does not seem to have any specific association with mitochondria or other organelles. As in the mammalian nephron, this ER organization is most likely related to specific segmental functions and adds support to its potential role as a transcellular epithelial route.


Sensitive detection of strong acidic condition by a novel rhodamine-based fluorescent pH chemosensor.
A novel rhodamine-based fluorescent pH probe responding to extremely low pH values has been synthesized and characterized. This probe showed an excellent photophysical response to pH on the basis that the colorless spirocyclic structure under basic conditions opened to a colored and highly fluorescent form under extreme acidity. The quantitative relationship between fluorescence intensity and pH value (1.75-2.62) was consistent with the equilibrium equation pH = pKa + log[(Imax - I)/(I - Imin)]. This sensitive pH probe was also characterized with good reversibility and no interaction with interfering metal ions, and was successfully applied to image Escherichia coli under strong acidity.


Lack of prognostic value of human epidermal growth factor-like receptor 2 status in inflammatory breast cancer (IBC): a meta-analysis.
Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/ neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.


Enhanced measurement of tiny rotational angles using conjugate orbital angular momentum modes.
We report the enhanced experimental measurement of tiny rotational angles using two conjugate OAM modes upon rotation of a Dove prism. The two conjugate OAM modes interfere in a petal-like pattern and the orientation of the pattern depends on the phase difference between the two modes. We propose an accurate method of digital image processing to measure the tiny rotational angles of the Dove prism. In the presence of an imperfect pattern and light path, the measurement precision was enhanced by a factor of l. This scheme has potential applications in high-precision sensing and monitoring of tiny rotation angles.


Superfluid liquid helium control for the primordial inflation polarization explorer balloon payload.
The Primordial Inflation Polarization Explorer (PIPER) is a stratospheric balloon payload to measure the polarization of the cosmic microwave background. Twin telescopes mounted within an open-aperture bucket dewar couple the sky to bolometric detector arrays. We reduce detector loading and photon noise by cooling the entire optical chain to 1.7 K or colder. A set of fountain-effect pumps sprays superfluid liquid helium onto each optical surface, producing helium flows of 50-100 cm3 s-1 at heights up to 200 cm above the liquid level. We describe the fountain-effect pumps and the cryogenic performance of the PIPER payload during two flights in 2017 and 2019.


[The effects of a computer assisted cognitive training on neuropsychological parameters, mood and dysfunctional cognitions in depressive patients].
In this pilot study a computer-assisted cognitive training programme (CAT) was tested and evaluated in patients with depressive syndromes for its effects on neuropsychological parameters, modd and dysfunctional cognitions. A total of 48 patients were randomized either to the treatment or the control group. The former underwent 20 sessions, 30-45 minutes each, of computer-assisted cognitive training, twice a week. At the beginning and at the end of the training (ten weeks later), both groups were given neuropsychological tests (memory, attention, concentration and information processing speed) and also questionnaires to assess depressive mood, thoughts, negative self communication and locus of control. At the start of the study, both the groups information processing speed. All these were absent in the control group. Also the depressive mood, as well as negative self-communication markedly improved in the training group. As expected, these results were not observed in the control group. According to these results in depressed patients a computer-assisted cognitive training programme might have a positive influence not only on their neuropsychological functions but also on their dysfunctional beliefs. Thus CAT should be part of the treatment of depressive patients.


Isolated to integrated: an evolving medical informatics curriculum.
A library-led introductory informatics theme has been part of the Albany Medical College undergraduate medical school curriculum as a concurrent theme since 1993. Initially, classes were limited to large group sessions focusing on general searching skills. Over the past several years, course content has been expanded and increasingly integrated into other themes and clerkships. Web-based self-paced tutorials have replaced many classroom sessions, and Web 2.0 technologies have been introduced. Collaborations with clinical and basic science faculty in other themes supplement and strengthen the theme.


Evidences in favour of a single electron transfer (SET) mechanism in the TiO2 sensitized photo-oxidation of α-hydroxy- and α,β-dihydroxybenzyl derivatives in water.
The TiO(2) photosensitized oxidation in water of a series of X-ring substituted benzyl alcohols gives the corresponding benzaldehyde. Kinetic evidence (from competitive experiments) suggests a single electron transfer (SET) mechanism with a changeover of the electron abstraction site from the aromatic moiety (X=4-OCH(3), 4-CH(3), H and 3-Cl) to the hydroxylic group (X=3-CF(3) and 4-CF(3)), probably due to the preferential adsorption of the above OH group on the TiO(2) surface. The same photo-oxidation of a series of 1-(X-phenyl)-1,2-ethanediols and of 2-(X-phenyl)-1,2-propanediols gives the corresponding benzaldehyde and acetophenone, respectively, accompanied by formaldehyde, whereas a series of symmetrically X-ring-substituted 1,2-diphenyl-1,2-ethanediols yields the corresponding benzaldehyde (substrate/product molar ratio=0.5). The relative rate values suggest a SET mechanism in all of the series, with electron abstraction from one of the two OH groups of all the considered diols, probably due to the much higher adsorption of the above groups (due to the chelation effect) on the semiconductor. Further confirmation of this mechanistic behaviour has been obtained from laser flash photolysis experiments.


Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012-2013.
The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results.


High-fidelity national carbon mapping for resource management and REDD+.
High fidelity carbon mapping has the potential to greatly advance national resource management and to encourage international action toward climate change mitigation. However, carbon inventories based on field plots alone cannot capture the heterogeneity of carbon stocks, and thus remote sensing-assisted approaches are critically important to carbon mapping at regional to global scales. We advanced a high-resolution, national-scale carbon mapping approach applied to the Republic of Panama - one of the first UN REDD + partner countries. Integrating measurements of vegetation structure collected by airborne Light Detection and Ranging (LiDAR) with field inventory plots, we report LiDAR-estimated aboveground carbon stock errors of ~10% on any 1-ha land parcel across a wide range of ecological conditions. Critically, this shows that LiDAR provides a highly reliable replacement for inventory plots in areas lacking field data, both in humid tropical forests and among drier tropical vegetation types. We then scale up a systematically aligned LiDAR sampling of Panama using satellite data on topography, rainfall, and vegetation cover to model carbon stocks at 1-ha resolution with estimated average pixel-level uncertainty of 20.5 Mg C ha-1 nationwide. The national carbon map revealed strong abiotic and human controls over Panamanian carbon stocks, and the new level of detail with estimated uncertainties for every individual hectare in the country sets Panama at the forefront in high-resolution ecosystem management. With this repeatable approach, carbon resource decision-making can be made on a geospatially explicit basis, enhancing human welfare and environmental protection.


Seroprevalence of HbsAg, Anti-HBc and anti-HCV in Southern Brazil, 1999-2001.
The prevalence of infection by the hepatitis B (HBV) and C (HCV) viruses varies among geographical regions. We evaluated 263,795 blood donor samples collected from 1999-2001 in various cities in the state of Santa Catarina to determine the prevalence of HbsAg, anti-HBc and anti-HCV markers. The markers were analyzed by immunoenzymatic tests, as determined by the Ministry of Health, and the data were obtained from blood banks and from ANVISA (the Brazilian National Agency for Sanitary Vigilance). There was a significant reduction in the mean frequency of HbsAg and anti-HBc during the study period, from 0.98% to 0.64% and from 8.83% to 5.35%, respectively, though they varied considerably among the different regions. There was also a decrease in the mean frequency of anti-HCV, although it was not significant, decreasing from 0.38% to 0.34%. Even with this reduction, the frequency of these markers was still high compared with that found in other countries, indicating high rates of infection by hepatitis B and C viruses. This emphasizes the urgency of vaccination programs against HBV, especially in some regions of Santa Catarina state, in order to reduce the prevalence of this infection and consequently reduce the risk of transmission through sexual relations or from the donation of blood and/or hemocomponents.


Birth weight and renal function.
Low birth weight due to premature birth or to intrauterine growth retardation adversely affects normal renal development. In the period immediately after birth, the short-term renal-related consequences of low birth weight are an increased risk of acute renal failure as well as transient imbalance of fluid and electrolyte homeostasis. Epidemiological studies show that low birth weight adults are at risk of developing chronic renal disease. There are thought to be several causes for this phenomenon. Adult low birth weight subjects have an increased incidence of hypertension and type 2 diabetes, both of which are well-established risk factors for chronic renal injury. Moreover, interference with normal kidney development, as seen in low birth weight babies, results in a lower than normal number of nephrons, which might also play a role in the renal disturbances.


The antimicrobial peptide DEFB1 is associated with caries.
Genetics is an important component in the determination of individual susceptibility to caries and periodontal diseases. Since beta defensin 1 (DEFB1) localizes in the oral cavity, we tested if variation in DEFB1 is associated with caries and periodontitis. We analyzed 3 single-nucleotide polymorphisms in DEFB1 in DNA samples from unrelated individuals. Carrying a copy of the variant allele of the DEFB1 marker rs11362 (G-20A) increased the DMFT and DMFS scores more than five-fold. Also, carrying a copy of the variant allele of the DEFB1 marker rs179946 (G-52A) correlated with low DMFT scores. We found a high-caries-experience haplotype (GCA), which increased DMFT scores two-fold, and a low- caries-experience haplotype (ACG), which decreased DMFT scores two-fold, in the DEFB1 promoter. No association between DEFB1 genetic markers and periodontal disease was found. Our results suggest that functional polymorphisms of DEFB1 are potential markers for caries.


The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.
Memantine has been demonstrated to be safe and effective in the symptomatic treatment of Alzheimer's disease (AD). While the neurobiological basis for the therapeutic activity of memantine is not fully understood, the drug is not a cholinesterase inhibitor and, therefore, acts differently from current AD therapies. Memantine can interact with a variety of ligand-gated ion channels. However, NMDA receptors appear to be a key target of memantine at therapeutic concentrations. Memantine is an uncompetitive (channel blocking) NMDA receptor antagonist. Like other NMDA receptor antagonists, memantine at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory. However, at lower, clinically relevant concentrations memantine can under some circumstances promote synaptic plasticity and preserve or enhance memory in animal models of AD. In addition, memantine can protect against the excitotoxic destruction of cholinergic neurons. Blockade of NMDA receptors by memantine could theoretically confer disease-modifying activity in AD by inhibiting the "weak" NMDA receptor-dependent excitotoxicity that has been hypothesized to play a role in the progressive neuronal loss that underlies the evolving dementia. Moreover, recent in vitro studies suggest that memantine abrogates beta-amyloid (Abeta) toxicity and possibly inhibits Abeta production. Considerable attention has focused on the investigation of theories to explain the better tolerability of memantine over other NMDA receptor antagonists, particularly those that act by a similar channel blocking mechanism such as dissociative anesthetic-like agents (phencyclidine, ketamine, MK-801). A variety of channel-level factors could be relevant, including fast channel-blocking kinetics and strong voltage-dependence (allowing rapid relief of block during synaptic activity), as well as reduced trapping (permitting egress from closed channels). These factors may allow memantine to block channel activity induced by low, tonic levels of glutamate--an action that might contribute to symptomatic improvement and could theoretically protect against weak excitotoxicity--while sparing synaptic responses required for normal behavioral functioning, cognition and memory.


[Intraprostatic spiral for the treatment of benign prostatic hypertrophy. A new method of insertion with sonographic monitoring. Apropos of 35 patients].
The treatment of subvesical obstruction with a spiral endoprostatic prosthesis is now well-known since Fabian's initial work (1980). A new method of insertion of the spiral with a releasable catheter and under sonographic monitoring has been proposed recently. This article is a report of a series of 35 patients. These patients presented with an adenoma of the prostate and were fitted with a permanent urethral catheter due to an absolute contraindication for anesthesia. The spiral was inserted with US monitoring in 25 patients. In 5 patients, the spiral had to be inserted under classical endoscopic control. The average follow-up period is 7.2 months. In 25 patients (75%), the spiral remained in place; the maximum flow rate of urine after the insertion averages 12.8 ml/s and 76% of these patients report an improvement of their comfort during urination. The position of the spiral had to be changed in 8 cases. No infectious complication was noted. Hematuric complications are reported in 2 cases. The spiral endoprostatic prosthesis seems to be an elegant alternative to the permanent catheter in patients at high anesthetic risk.


The Hartford Consensus IV: A Call for Increased National Resilience.
Despite advances in the response to active shooter and intentional mass casualty events, a gap remains in our national preparedness and resilience. Drawing from experiences at myriad mass casualty events, the immediate responder (volunteer responder) represents an underutilized resource, yet one capable of dramatically increasing our all-hazards (injuries from all natural and man-made causes) national resilience. The overarching principle of the Hartford Consensus, outlined in previous reports, is that no one should die from uncontrolled bleeding. We have championed the following acronym to summarize what we have determined are appropriate steps to ensure that the maximum number of victims of these tragic events can be saved: THREAT: Threat suppression. Hemorrhage control. Rapid Extrication to safety. Assessment by medical providers. Transport to definitive care.


Palladium on Carbon-Catalyzed Benzylic Methoxylation for Synthesis of Mixed Acetals and Orthoesters.
The palladium on carbon (Pd/C)-catalyzed direct methoxylation of the benzylic positions of linear benzyl and cyclic ether substrates proceeded in the presence of i-Pr2 NEt under an oxygen atmosphere to give the corresponding mixed acetals. Cyclic acetal derivatives could also be converted into orthoesters. The present direct methoxylation via a carbon-hydrogen (C-H) functionalization can be accomplished using the easily-removed Pd/C and molecular oxygen as a green oxidant. The obtained mixed acetals were transformed into the corresponding ether products by chemoselective substitution of the methoxy group using a silyltriflate, 2,4,6-collidine, and a nucleophile. The orthoester derivative could also be transformed into the cyclic ketal under similar reaction conditions.


RAS Mutational Status Detection in Tissue, Plasma, and Stool Samples for Colorectal Cancer.
RAS gene testing on tumor tissue biopsies is required for metastatic colorectal cancer (CRC) patients. However, it is infeasible for patients after curative surgery and repeated biopsy. This study is aimed at evaluating the consistency of RAS genes in patient's plasma, stool, and tumor tissue samples, to explore whether plasma and stool samples can supplement or replace tumor tissue to assess baseline RAS gene status. Between June 2016 and October 2017, 53 patients with stage I-IV CRC from the Liaoning Cancer Hospital and the Department of Medical Oncology of the First Hospital of China Medical University were enrolled in the study. Patient tissues, peripheral blood, and stool samples were collected, and RAS gene tests were performed. Analysis of the KRAS gene in tissue, plasma, and stool samples from 53 CRC patients detected 25 cases (47%) of KRAS gene mutations in the tissue samples, 20 cases (38%) of KRAS gene mutations in plasma, and 18 (34%) KRAS gene mutations in fecal samples. The overall consistency of KRAS gene status between tissue samples and plasma samples was 77.4% (p ≤ 0.05) and between tissue samples and stool samples was 83% (p ≤ 0.05). In stage IV cases, the agreement of KRAS gene status between tissue and plasma samples was 93.8% (p ≤ 0.05) and 93.8% (p ≤ 0.05) between tissue and stool samples. There was a high overall consistency in KRAS mutational assessment between plasma, stool, and tissue samples. In stage IV patients, the consistency of KRAS gene detection between tissue and stools or plasma was higher.


Tick resistance and the major histocompatibility system.
199 3/4 Brahman 1/4 Shorthorn cattle, whose resistance to the cattle tick Boophilus microplus had been determined by clinical trial, were tested for 19 bovine lymphocyte antigens. Of eleven antigens detected at a frequency greater than 5%, two were found to be associated with tick resistance and a third was associated with susceptibility to ticks. However, none of these antigens accounts for more than 2.1% of the variance, indicating that these associations are not strong.


Frequency of feed delivery affects the behavior of lactating dairy cows.
The objectives of this study were to examine how frequency of feed delivery affects 1) the behavior of group-housed and group-fed dairy cows and 2) the extent of feed sorting. These objectives were tested in two experiments. In each experiment, 48 lactating Holstein cows, split into groups of 12, were subjected to each of 2 treatments (over 10-d periods) in a cross-over design. The treatments for the first experiment were 1) delivery of feed once per day (1x) and 2) delivery of feed twice per day (2x). Treatments for the second experiment were 1) delivery of feed 2x and 2) delivery of feed four times per day (4x). For the 1x, 2x, and 4x treatments, feed was pushed up 3, 2, and 0 times per day, respectively. For both experiments, cows had 0.6 m of feeding space; one cows was allowed per lying stall. Time-lapse video was used to quantify the feeding and lying behavior, as well as the aggressive behavior displayed at the feed bunk by the cows. Changes in NDF content of the TMR throughout the day were used to determine the extent of feed sorting by the cows. In both experiments, increased frequency of feed provision increased, as well as changed, the distribution of daily feeding time. The changes in distribution of feeding time resulted in cows having more equal access to feed throughout the day. Frequency of feed delivery had no effect on the daily lying time of the cows or the daily incidence of aggressive interactions at the feed bunk. However, subordinate cows were not displaced as frequently when fed more often. For all treatments, in both experiments, the NDF content of the TMR present in the feed bunk increased throughout the day, indicating that sorting of the feed had occurred. Further, the amount of sorting of the feed was reduced by increasing the frequency of feed delivery from 1x to 2x. These results indicate that frequent delivery of feed improves access to feed for all cows, particularly during peak feeding periods when fresh feed is provided, and reduces the amount of feed sorting.


Results of a Qualitative Study to Develop a Patient Reported Outcome Measure for Patients with 4 Subtypes of Soft Tissue Sarcoma.
The objective of this research was to develop a disease-specific symptom inventory for soft tissue sarcoma. Literature review and clinical expert and patient interviews were conducted to determine disease-specific symptoms important to patients with one of the four STS subtypes. Clinical experts identified the most relevant STS symptom items from the item pool developed from literature review. Concept elicitation interviews were conducted with patients to elicit their STS symptom experiences followed by a completion of the draft symptom list via web survey. A cognitive interview was conducted on the comprehension and importance of the symptom items. Eighty-three symptom items were compiled and discussed with three clinical experts who identified 26 symptoms specific to the four STS subtypes. A total sample of 27 STS participants with self-reported leiomyosarcoma (74%), undifferentiated sarcoma (15%), synovial sarcoma (7%), or liposarcoma (4%) diagnosis completed the web survey and 10 were interviewed. The draft 12-item STS-specific symptom inventory includes abdominal pain, pressure in abdomen, early satiety, bloating, gastrointestinal pain, muscle pain, bone pain, heavy menstrual flow, shortness of breath, chest pain, cough, and painful menstruation. A number of symptoms are common across STS subtypes and may form a single STS symptom inventory.


Oral lesions of lupus erythematosus patients in relation to other chronic inflammatory oral diseases: an immunologic study.
The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a+ and Leu 2a+) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined beta 2-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR greater than DQ greater than DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR much greater than DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (less than 5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.


Lysis of donor RBC during plateletpheresis with a blood processor.
Erythrocytes of a normal volunteer blood donor were grossly hemolyzed during plateletpheresis with the use of a continuous-flow centrifuge. Extensive studies of the donor's red blood cells (RBC) showed no abnormalities. Bank blood was then processed in the centrifuge in a manner identical to the prescribed in vivo plateletpheresis. Gross hemolysis consistently resulted when the tubing on the downstream side of the blood pump was partially obstructed by a twist. This experience calls for caution when assembling the harness of an extracorporeal circuit employing a pump. The tubing should be inspected to ensure the absence of obstructions.


Wavelet analysis of nonequilibrium ionic currents in human heart sodium channel (hH1a).
Nonequilibrium response spectroscopy (NRS), the technique of using rapidly fluctuating voltage pulses in the study of ion channels, is applied here. NRS is known to drive an ensemble of ion channels far from equilibrium where, it has been argued, new details of ion channel kinetics can be studied under nonequilibrium conditions. In this paper, a single-pulse NRS technique with custom-designed waveforms built from wavelets is used. The pulses are designed to produce different responses from two competing models of a human heart isoform of the sodium channel (hH1a). Experimental data using this new type of pulses are obtained through whole-cell recordings from mammalian cells (HEK 293). Wavelet analysis of the model response and the experimental data is introduced to show how these NRS pulses can aid in distinguishing the better of the two models and thus introduces another important application of this new technique.


Prediction of adult height: methods and problems.
The three commonly used methods of height prediction employ various combinations of anthropometric data and bone age. In normal children, the regression type methods are preferable, though they do not perform well in the more severe disorders of growth. They are extremely dependent upon the limitations of the method of bone age determination that is used. A major source of error is the inability to predict the timing or the intensity of the adolescent growth spurt. Until this proves possible it is unlikely that significant improvements can be made.


The treatment of gonorrhea, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale.
The "classic" venereal diseases are a diverse group of infections caused by established pathogens. Their epidemiologies are unique and relatively well understood. Likewise, the clinical presentations, although diverse, are well defined, allowing them to be readily suspected or diagnosed. Once the clinical diagnosis is considered, laboratory support methods are available to confirm the impression. This results in the provision of specific directed therapy that is curative. The spread of disease, however, must be considered, and the sexual partners must be identified, evaluated, and, where applicable, treated to prevent spread. The reinforcement of preventative methods is also an important aspect of controlling these infections.


Transcatheter aortic valve replacement for bicuspid aortic valve regurgitation in a 17-year-old patient with congenitally corrected transposition of great arteries: a case report.
Limited research has been conducted on the surgical management of the aortic valve in congenitally corrected transposition of great arteries (ccTGA) and to our knowledge there have been no reports on the treatment of bicuspid aortic regurgitation (AR) in ccTGA. We report on a ccTGA patient with bicuspid AR and systemic right ventricule (SRV) dysfunction who underwent transcatheter aortic valve replacement (TAVR). A 17-year-old male with a history of ccTGA and cerebral palsy diagnosed at birth presented with heart failure. During childhood, he did not experience any heart failure symptoms, however, secondary to progressive bicuspid AR he experienced worsening SRV dysfunction beginning at 15-year-old. Echocardiography showed reduced SRV ejection fraction and severe bicuspid AR. The heart team, including a cardiac surgeon and paediatric cardiologist, discussed the treatment strategies and decided to proceed with TAVR as surgical aortic valve replacement was deemed high risk. TAVR was performed with the 34 mm Evolut R (Medtronic, Minneapolis, MN, USA). Post-operative echocardiography showed severe paravalvular leak (PVL). Therefore, valve-in-valve TAVR using a 29 mm Edwards SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA) was performed on post-operative Day 2 for PVL reduction. Following second procedure, PVL was significantly improved. The patient was discharged in stable condition. This is the first case wherein TAVR was performed for bicuspid AR in a patient with ccTGA. With appropriate preparation and planning and a collaborative multi-disciplinary team approach, TAVR can be a treatment option for severe AR in patients with ccTGA at high risk for surgery.


Fronto-orbital reconstruction using polymethyl methacrylate implant.
The objective of this article is to show a case of fronto-orbital reconstruction with prefabricated polymethyl methacrylate prosthesis. A 35-year-old male with alleged history of trauma following road traffic accident 3 months back reported with unaesthetic scar and deformity in right supraorbital region to us. As there was no functional deformity, the management was aimed at correcting the contour and esthetic only. The correction was achieved by overlaying the defect with a polymethyl methacrylate implant fabricated over a three-dimensional stereolithographically printed rapidly prototyped model. Postoperative phase was uneventful and esthetic outcome was satisfactory. The patient after 4-year follow-up reported with no discomfort and definite improvement in facial contour.


Induction Effect to Apoptosis by Maitake Polysaccharide: Synergistic Effect of Its Combination With Vitamin C in Neuroglioma Cell.
Polysaccharide extracted from the Maitake mushroom (MP) is considered as a potential anticancer agent. The present study was performed to investigate the cytotoxic effects of MP and vitamin C (VC) alone and in combination on the viability of human neuroglioma M059 K cells in vitro. A combination of MP (1.0 mg/mL) and VC (0.4 mmol/L) led to a 53.10% reduction in cell viability and this treatment induced cell cycle arrest at the G2/M phase, and apoptosis occurred in 38.54% of the cells. Results of Hoechst 33258 staining and Western blot showed apoptotic cells appeared and changes in the expression of apoptosis-related proteins (upregulation of Bax and caspase-3, downregulation of Bcl-2, and activation of poly-(ADP-ribose)-polymerase). Moreover, the activities of caspase-3, caspase-8, and caspase-9 were enhanced in M059 K cells. The inhibiting effect of combined treatment with MP and VC on M059 K cells indicates the mechanism of anticancer activity involved induction of cell apoptosis.


Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals.
Successful therapy of bacterial meningitis is dependent upon achieving adequate antibacterial activity in the CSF. The percent penetration (CSF concentration/serum concentration X 100) of various antimicrobial agents was determined in a rabbit model of bacterial meningitis. The percent penetration of the penicillin and cephalosporin derivatives was found to vary inversely with the protein binding of the respective drugs. Esterification of ampicillin increased its lipid solubility and likewise increased the penetration into the CSF. Probenecid competitively inhibits the active transport efflux of various organic acids from the CSF and increased the CSF concentrations of penicillin and cephalosporin derivatives. The percent penetration of all drugs was increased in the presence of the inflamed meninges.


Development of antivirulence compounds: a biochemical review.
There is an urgent requirement for new anti-infective compounds that can be used to prevent or treat bacterial pathogens. In particular, Gram-negative pathogens, which are most commonly associated with hospital-acquired infections, are of major concern. In this review, we cover recent developments in the screening and testing of new anti-infective compounds that interfere with aspects of bacterial pathogenicity. This so-called antivirulence approach is very different to traditional antibiotic development and testing. Moreover, antivirulence compounds vary considerably in their chemical structures, ranging from small compounds to large natural products. The challenge of understanding the precise mechanism of action of any such compound is also highlighted.


Neural mechanisms controlling jaw-jerk reflex in the cat.
Signal substances of axon terminals presynaptic to jaw spindle Ia afferents and their ultrastructural features were examined using a combination of intra-axonal horseradish peroxidase injection and postembedding immunogold-labeling techniques in cats. A total of 35 axon terminals presynaptic to 22 horseradish peroxidase-labeled Ia boutons were examined. Of the 35 presynaptic axon terminals, 14 (40%) were immunoreactive for both gamma-aminobutyric acid and glycine, 9 (26%) for gamma-aminobutyric acid alone and 9 (26%) for glycine alone. The bouton volume, mitochondrial volume, active zone area, and apposed surface area were larger for Ia boutons than for presynaptic axon terminals, while each of the values is similar among the three types of presynaptic axon terminals. These results suggest that gamma-aminobutyric acid and glycine play an important role for modulating the jaw-jerk reflex presynaptically and that the smaller size of presynaptic axon terminals is important to prevent action potential generation from Ia afferents.


Correlations between subjective rating and objective assessment of balance function in individuals with stroke.
To examine the relationships among therapist-reported, patient-reported, and objective assessment scores of balance function. Inpatients with stroke and occupational therapists were recruited. The objective balance scores were measured using the Balance Computerized Adaptive Testing (Balance CAT) system. The therapist and patient-reported scores were evaluated using a visual analogue scale (VAS) and Likert-type scale. Eighty-eight patients and 16 therapists participated. The correlations (r= 0.64 and 0.65; R-squared about 0.42 at baseline and follow-up assessments, respectively) between the therapist-reported VAS scores and the Balance CAT system were larger than those (r = 0.31 and 0.21) between the patient-reported VAS scores and the Balance CAT system. Low correlations (r = 0.27 and 0.26 for VAS and Likert-type scores, respectively) were found between the therapist-reported and patient-reported change scores. Low correlations (r = 0.12-0.17) were found between the change scores of therapist- and patient-reported ratings and those of the Balance CAT system. The therapists' judgments explained <50% of variance of the Balance CAT system scores. Neither therapist-reported nor patient-reported change scores reflected the changes demonstrated by the objective assessments. Further studies are warranted to confirm our findings.Implications for RehabilitationNeither therapist- nor patient-reported balance function and change could effectively reflect the scores resulting from objective assessments.The routine use of objective balance assessments should not be replaced by therapists' subjective judgments.Communications regarding the balance function measured by objective assessments between therapists and patients can help patients to better understand their balance function and progress.


A novel alpha kinase EhAK1 phosphorylates actin and regulates phagocytosis in Entamoeba histolytica.
Phagocytosis plays a key role in nutrient uptake and virulence of the protist parasite Entamoeba histolytica. Phagosomes have been characterized by proteomics, and their maturation in the cells has been studied. However, there is so far not much understanding about initiation of phagocytosis and formation of phagosomes at the molecular level. Our group has been studying initiation of phagocytosis and formation of phagosomes in E. histolytica, and have described some of the molecules that play key roles in the process. Here we show the involvement of EhAK1, an alpha kinase and a SH3 domain containing protein in the pathway that leads to formation of phagosomes using red blood cell as ligand particle. A number of approaches, such as proteomics, biochemical, confocal imaging using specific antibodies or GFP tagged molecules, expression down regulation by antisense RNA, over expression of wild type and mutant proteins, were used to understand the role of EhAK1 in phagocytosis. EhAK1 was found in the phagocytic cups during the progression of cups, until closure of phagosomes, but not in the phagosomes themselves. It is recruited to the phagosomes through interaction with the calcium binding protein EhCaBP1. A reduction in phagocytosis was observed when EhAK1 was down regulated by antisense RNA, or by over expression of the kinase dead mutant. G-actin was identified as one of the major substrates of EhAK1. Phosphorylated actin preferentially accumulated at the phagocytic cups and over expression of a phosphorylation defective actin led to defects in phagocytosis. In conclusion, we describe an important component of the pathway that is initiated on attachment of red blood cells to E. histolytica cells. The main function of EhAK1 is to couple signalling events initiated after accumulation of EhC2PK to actin dynamics.


Detection of small numbers of cells characteristic for haematological disorders in peripheral blood (the deep diff).
We studied cytocentrifuge preparations of peripheral blood mononuclear leucocytes in haematological patients with nondiagnostic white cell differential counts. This approach (the 'deep diff') enabled the detection of small numbers of diagnostically significant cells in a majority of patients. We found ringed sideroblasts in 5/7 patients with sideroblastic anaemia and megaloblasts in 9/10 patients with megaloblastic anaemia. We observed centrocytes in seven patients with follicular lymphoma, mantle cells in five patients with mantle cell lymphoma and marginal zone cells in five patients with nodal marginal zone lymphoma. We detected small percentages of lymphoma cells in cytospins of mononuclear leucocytes in 12 patients with large B-cell lymphoma, Burkitt's lymphoma and anaplastic large-cell lymphoma. The deep diff was nondiagnostic in 5/6 patients with hairy cell leukaemia and in 9/10 patients with Waldenström's macroglobulinaemia and small lymphocytic lymphoma. In these cases, there were insufficient cells to detect light chain restriction. Increased counts of leukaemic cells were found in 12/13 patients with acute leukaemia with < 3% blasts in the conventional white cell differential. Increased blasts were also observed in six patients with refractory anaemia with excess of blasts (RAEB). Decreased blasts were found in five patients with aplastic anaemia and in nine patients with bone marrow aplasia after intensive chemotherapy. Increased plasma cell counts were observed in 13/14 patients with advanced plasma cell myeloma. We conclude that the 'deep diff', augmented by immunocytochemistry, may be useful in the diagnosis of haematological disorders.


[Multiple cerebral infarcts caused by spontaneous, synchronous cholesterol embolisms].
We report on a 68-year-old patient who was admitted with hemiparesis and disorientation. Computed tomography showed several old, mostly lacunar infarcts. One week after admission, the patient became comatose. A repeat computed tomography revealed several new hypodense lesions in both hemispheres compatible with acute cerebral infarctions. Autopsy confirmed the diagnosis of numerous acute encephalomalacias of the same age which were found in different territories of the anterior cerebral circulation. Histologic examination showed the extraordinary result of multiple cholesterol emboli with a maximum in the peripheral leptomeningeal vessels. The source of the emboli was severe atherosclerosis with an ulcerated and thrombotic surface of the aorta and both carotid arteries. This case is remarkable because of its severe and synchronous emboli of cholesterol in several different cerebral territories. One has to suspect a so far unknown physical or metabolic factor responsible for the shower of emboli.


Mammary glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion.
Adipophilin (ADPH), a member of the perilipin family of lipid droplet-associated proteins, is hypothesized to mediate milk lipid formation and secretion. Unexpectedly, the fat content of milk from ADPH-null mice was only modestly lower than that of wild-type controls, and neither TIP47 nor perilipin appeared to fully compensate for ADPH loss. This prompted us to investigate the possibility that the mutated ADPH gene was not a genuine null mutation. ADPH transcripts were detected in ADPH-null mammary tissue by quantitative real-time PCR, and C-terminal-specific, but not N-terminal-specific, ADPH antibodies detected a single lower molecular weight product and immunostained cytoplasmic lipid droplets (CLDs) and secreted milk fat globules in ADPH-null mammary tissue. Furthermore, stable cell lines expressing cDNA constructs corresponding to the ADPH-null mutation produced a product comparable in size to the one detected in ADPH-null mammary glands and localized to CLDs. Based on these data, we conclude that ADPH-null mice express an N-terminally truncated form of ADPH that retains the ability to promote the formation and secretion of milk lipids.