Inhibition of influenza virus internalization by (-)-epigallocatechin-3-gallate.
(-)-Epigallocatechin-3-gallate (EGCG), one of the major flavonoid components of green tea, is known to have a broad antiviral activity against several enveloped viruses, including the influenza virus. However, its mode of action and the mechanism that allows it to target influenza virus molecules have not been fully elucidated. Thus, this study investigated the molecular mechanism by which EGCG suppresses influenza virus infections. EGCG was found to block an early step in the influenza viral life cycle, but it did not affect viral adsorption to target cells or viral RNA replication. However, EGCG inhibited hemifusion events between virus particles and the cellular membrane by reducing the viral membrane integrity, thereby resulting in the loss of the cell penetration capacity of the influenza virus. EGCG also marginally suppressed the viral and nonviral neuraminidase (NA) activity in an enzyme-based assay system. In conclusion, it is suggested that the anti-influenza viral efficacy of EGCG is attributable to damage to the physical properties of the viral envelope and partial inhibition of the NA surface glycoprotein. These results may facilitate future investigations of the antiviral activity of EGCG against other enveloped viruses as well as influenza virus.


Proportion of undetected narrow angles or angle closure in cataract surgery referrals.
To determine the proportion of patients referred for cataract surgery consultation who had undetected narrow angles (primary angle closure suspect [PACS], primary angle closure [PAC], or primary angle closure glaucoma [PACG]). Retrospective chart review. Phakic patients referred by eye care providers (optometrists and ophthalmologists) to a tertiary centre for cataract management between July 1, 2010 and June 30, 2012 were identified and reviewed. Demographic, referral, and specialist assessment information, as well as biometric data, including anterior segment optical coherence tomography, were collected. Patients with undetected narrow angles were identified. Univariate tests and multivariable analyses were performed to determine risk factors for narrow angles or angle closure. A total of 1229 patients were included. The mean patient age was 67.8 ± 13.0 years, 53.9% of patients were female, and 26.8% were Asian or South Asian. Of the sample population, 139 (11.3%) patients had PACS, 7 (0.6%) had PAC, and 12 (1.0%) had PACG. Overall, 158 (12.9%) patients had narrow angles or angle closure. Multivariable logistic regression using generalized estimating equations confirmed 3 independent predictors of PACS/angle closure: Asian race (odds ratio 2.82, p < 0.001), shorter axial length (AL) (odds ratio 1.25, p = 0.03), and smaller anterior chamber depth (ACD; odds ratio 33.3, p < 0.001). A patient of Asian race referred for cataract surgery with ACD <2.8 mm and AL <23 mm had a 52% probability of having PACS/angle closure (range 42%-62%) versus 3% if these 3 factors were not present. Of patients referred for cataract surgery, 1.5% were found to have undetected narrow angles or angle closure, implying that gonioscopy may not be adequately performed in this patient population.


Enhancing the Sound and Thermal Insulation Properties of Polypropylene Foam by Preparing High Melt Strength Polypropylene.
High-performance polypropylene (PP) foam is a vital polymer product in industrial areas. However, the poor melt strength of ordinary PP homopolymer limits its foaming molding. In this work, high melt strength polypropylene (HMSPP) is prepared by using styrene (St) and tripropylene glycol diacrylate (TPGDA) as comonomers, and then PP foams are prepared by mold foaming method. The results show that adding St in the grafting process of TPGDA will obviously improve the melt strength of the PP matrix, and its melt strength (28 184 Pa.s) is 7.4 times higher than that of pure PP. HMSPP foam has more regular and uniform cells and higher cell density, which significantly improves the sound and thermal insulation properties of PP foam. Compared with pure PP foam, the average sound transmission loss (52.9 dB) of HMSPP foam with a low foaming ratio increased by 64%, and the thermal conductivity (0.0867 W mK-1 ) decreased by 46%. Therefore, the obtained HMSPP foam can be used in sound insulation or thermal insulation area. This work provides an available route for the high-performance utilization of PP foam.


Feasibility of Dose Escalating [18F]fluciclovine Positron Emission Tomography Positive Pelvic Lymph Nodes During Moderately Hypofractionated Radiation Therapy for High-Risk Prostate Cancer.
The aim of this study was to report the treatment planning feasibility of dose escalation to suspicious lymph nodes (LNs) for a series of men who underwent pretreatment [18F]fluciclovine positron emission tomography (PET)/magnetic resonance imaging (MRI). Cases of men with prostate cancer who enrolled in a clinical trial of pretreatment [18F]fluciclovine PET who had suspicious LNs were selected. Pelvic LNs <1 cm were defined as positive based on [18F]fluciclovine-PET if their maximum standardized uptake value (SUVmax) was ≥1.3-fold greater than the reference blood pool SUVmean, and LNs ≥1 cm were defined as positive if the SUV was greater than the reference SUV bone marrow reference. For each case, a radiation treatment plan was generated to deliver 70 Gy to the prostate and proximal seminal vesicles, 60.2 Gy to the PET-positive LNs, and 50.4 Gy to the elective nodal regions, simultaneously in 28 fractions of 2.5 Gy, 2.15 Gy, and 1.8 Gy, respectively. Treatment planning goals were defined a priori. The resulting target volume and organ-at-risk dosimetry were compared with the original treatment plan. Four cases were identified, with between 1 and 5 [18F]fluciclovine PET-positive LNs each. Goals for the prostate and elective nodal target volumes were successfully met in all cases. The goal of covering more than 90% of the positive LN planning target volume by the prescription dose of 60.2 Gy was met in 3 of the 4 cases. This goal was not met in 1 case, but 100% of clinical target volume was covered by 60.2 Gy. The primary organ-at-risk tradeoff was that a small volume (0.5-8.2 cm3) of small bowel would receive ≥54 Gy in each case. These preliminary results suggest that [18F]fluciclovine PET/MRI directed dose escalation of suspicious pelvic LNs is likely feasible in the setting of definitive radiation therapy. The potential clinical benefit of dose escalating [18F]fluciclovine PET-positive LNs should be investigated in a prospective clinical trial.


Exposure to organophosphate flame esters during early pregnancy and risk of spontaneous abortion: A case-control study.
Prenatal exposure to organophosphate flame retardants (OPFRs) has been associated with adverse pregnancy outcomes including low birth weight and preterm birth. However, no study has addressed the impacts of OPFRs exposure on spontaneous abortion (SAB) and fetal chromosome abnormalities. We examined whether prenatal exposure to OPFRs was associated with increased risk of SAB and fetal chromosome abnormalities. A total of 272 pregnant women, including 136 SAB cases and 136 healthy controls, were enrolled in this case-control study. Urinary concentrations of 3 OPFRs metabolites (diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCIPP) and bis (1-chloro-2-propyl) phosphate (BCIPP)) were measured using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). More than 70% of the urine samples detected quantifiable levels of 3 OPFRs metabolites. Concentrations of BCIPP were significantly higher in SAB cases than in healthy controls. Higher urinary BCIPP levels were associated with increased risk of SAB. Per unit increase in ln-transformed BCIPP concentrations was associated with 103% (OR = 2.03, 95% CI, 1.57, 2.63) increase in the odds of SAB. While higher BDCIPP levels were associated with increased risk of fetal chromosome abnormalities and the corresponding OR associated with a unit increase in ln-transformed BDCIPP concentrations were 2.34 (95% CI, 1.14, 4.81). Our results suggested the potential developmental toxicity and teratogenicity of some OPFRs.


Dustborne Alternaria alternata antigens in US homes: results from the National Survey of Lead and Allergens in Housing.
Alternaria alternata is one of the most common fungi associated with allergic disease. However, Alternaria exposure in indoor environments is not well characterized. The primary goals of this study were to examine the prevalence of Alternaria exposure and identify independent predictors of Alternaria antigen concentrations in US homes. Data for this cross-sectional study were obtained from the National Survey of Lead and Allergens in Housing. A nationally representative sample of 831 housing units in 75 different locations throughout the United States completed the survey. Information on housing and household characteristics was obtained by questionnaire and environmental assessments. Concentrations of A alternata antigens in dust collected from various indoor sites were assessed with a polyclonal anti-Alternaria antibody assay. Alternaria antigens were detected in most (95% to 99%) of the dust samples. The geometric mean concentration, reflecting the average Alternaria concentration in homes, was 4.88 microg/g (SEM, 0.13 microg/g). In the multivariable linear regression analysis, the age of the housing unit, geographic region, urbanization, poverty, family race, observed mold and moisture problems, use of de-humidifier, and presence of cats and dogs were independent predictors of Alternaria antigen concentrations. Less frequent cleaning and smoking indoors also contributed to higher Alternaria antigen levels in homes. Exposure to A alternata antigens in US homes is common. Antigen levels in homes are influenced not only by regional factors but also by residential characteristics. Preventing mold and moisture problems, avoiding smoking indoors, and regular household cleaning may help reduce exposure to Alternaria antigens indoors.


In-silico identification of adsorbent for separation of ethane/ethylene mixture.
We present here a high-throughput computational screening of 4,821 real metal-organic framework (MOF) structures that do not contain any open metal sites to isolate the best performing candidate for separation of ethane/ethylene mixture at ambient conditions. The MOF structures were assessed on the basis of several adsorption-based separation performance metrics. Some of these metrics were found to correlate strongly among themselves. We have presented various structures-property correlations which unfold useful insights. MOF ATAGEJ is found to be the top performing MOF with highest adsorbent performance score 12.38 mol/kg and regenerability 93.88%. Several other MOFs OTOLIU (MIL-167), UMUMOG (UBMOF-8), and TOVGES (PCN-230) containing tetravalent metal cations such as Zr4+ and Ti4+ are found to be potential structures that are thermally, mechanically, and chemically stable and performs better than zeolites. Adsorption selectivity shows exponential correlation with difference of heat of adsorption of ethane and ethene at 0.1 bar and 298 K. We have also presented how various performance metrics correlate among themselves. These correlations unfold useful insights. Graphical abstract.


Corporate social responsibility in times of need: Community support during the COVID-19 pandemics.
Since the outbreak of COVID-19, the hotel sector has engaged in various corporate social responsibility (CSR) initiatives to show solidarity with local communities. Our research examines the impact of such initiatives on tourists' intentions to spread positive word-of-mouth (WOM) and their intentions to visit when the current pandemic ends. Our experimental results suggest community support in the form of providing free accommodation to homeless people increases tourists' intentions to spread positive WOM, bringing reputational benefits. But such initiatives reduce tourists' intentions to visit, presenting potential business risks. Our results further suggest that community support in the form of providing free accommodation to medical professionals has little impact, as it shows no significant difference to control (no CSR initiatives).


The role of neuropeptide Y in energy homeostasis.
When administered into the brain, NPY acts at Y1 and Y5 receptors to increase food intake. The response occurs with a short latency and is quite robust, such that exogenous NPY is generally considered to be the most potent of a growing list of orexigenic compounds that act in the brain. The role of endogenous NPY is not so straightforward, however. Evidence from diverse types of experiments suggests that rather than initiating behavioral eating per se, endogenous NPY elicits autonomic responses that prepare the individual to better cope with consuming a calorically large meal.


Vitamin D replacement therapy in persons with spinal cord injury.
An increased prevalence of vitamin D deficiency has been reported in persons with chronic spinal cord injury (SCI), but treatment guidelines for replacement are not available. The purpose of this study was to evaluate two types of vitamin D therapy on calcium metabolism and vitamin D status in persons with SCI. Ten subjects with chronic SCI who were vitamin D deficient received 25 hydroxyvitamin D3 [25(OH)D], 50 microg twice a week, for 14 days (Study 1). Regardless of vitamin D status, 40 subjects received vitamin D3 800 IU (20 microg) daily for 12 months (Study 2). Supplemental calcium was administered. The response to therapy was determined by the effect upon serum 25(OH)D levels. Results are expressed as mean +/- standard deviation. In Study 1, serum 25(OH)D levels increased by day 14 (8.7 +/- 2.1 vs 14.7 +/- 3.6 ng/mL; P < 0.0005). However, in 8 of 10 subjects, 25(OH)D levels were still below the absolute lower limit of normal. Serum calcium levels were not significantly different, but urinary calcium excretion increased (103 +/- 81 vs 184 +/- 145 mg/d; P < 0.01). Serum parathyroid hormone (PTH) levels decreased (35 +/- 26 vs 1 7 +/- 12 pg/ mL; P < 0.01). In Study 2, after 12 months of vitamin D supplementation, 9 subjects had an absolute and 23 had a relative vitamin D deficiency, compared with 33 and 6 subjects, respectively, at baseline. By 12 months, the 25(OH)D level increased (10.7 +/- 7.1 to 22.5 +/- 7.5 ng/mL; P < 0.0001) and the serum PTH level decreased (37 +/- 16 vs 25 +/- 11 pg/mL; P < 0.0001). Although 25(OH)D levels significantly increased in both studies, the replacement therapies employed were not sufficient to recommend for adoption for clinical use, indicating the need for higher doses and/or for longer periods of administration.


Whole-Genome Draft Sequences of Three Multidrug-Resistant Klebsiella pneumoniae Strains Available from the American Type Culture Collection.
Infection with multidrug-resistant Klebsiella pneumoniae is a significant problem worldwide, requiring a better understanding of how various strains are able to defeat current antibiotic therapies and cause disease. Here, we report the draft genome sequences of three K. pneumoniae strains harboring the SHV-18, KPC-2, or NDM-1 β-lactamases.


Recombination after protoplast fusion in the yeast Candida tropicalis.
Candida tropicalis protoplasts obtained by snail enzyme treatment were induced to fuse by the use of polyethylene-glycol. Heterokaryons formed by two auxotrophic strains were selected by complementation on minimal medium. These heterokaryons were unstable and readily dissociated into their nuclear components. Under appropriate conditions, the parental nuclei of an heterokaryon fused. The homokaryon so obtained was unstable and segregated into various types of auxotrophic and prototrophic recombinants.


Inflammatory activation biomarker profile after marathon running and its impact on cardiovascular stress in amateur middle-aged male runners.
Cardiovascular safety of marathon running middle-aged amateurs remains unclear. We previously hypothesized that transient release of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in addition to an acute inflammatory response to exercise, may be the cause. To evaluate the effects of running a marathon on inflammatory biomarkers, and its impact on cardiovascular function. Thirty-three healthy male amateur runners aged ≥50 (mean age: 57 ±7 years) were enrolled in the study. Venous blood samples were obtained before the marathon, just after the race, and 2-4 days and 7 days after the marathon. Using novel single molecule counting (SMC) technology, we measured plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). White blood cell (WBC) count was measured using a certified hematology analyzer. The results were related to previous analyses on cardiovascular stress and endothelial function biomarkers. Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were used to determine myocardial function. We observed a sharp rise of all studied biomarkers after the race, which subsequently normalized after 2-4 days and stayed within the normal range 7 days after the race. We found no correlation between inflammatory and cardiovascular stress biomarkers. Transthoracic echocardiography and CMR did not show ischemic or inflammatory myocardial damage. Marathon running is associated with a sharp and significant rise in inflammatory and cardiovascular stress biomarkers. We found no connection between immune activation and cardiac biomarker release. Cardiovascular imaging showed no myocardial damage due to ischemia or inflammation.


The people behind the papers - Milica Bulajić, Divyanshi Srivastava, Esteban Mazzoni and Shaun Mahony.
Hox genes instruct positional identity along the anterior-posterior axis of the animal body. A new paper in Development addresses the question of how similar Hox genes can define diverse cell fates, using mouse motor neurons as a model. To hear more about the work, we caught up with the paper's two first authors, PhD students Milica Bulajić and Divyanshi Srivastava, and their respective supervisors Esteban Mazzoni (Associate Professor of Biology at New York University, USA) and Shaun Mahony (Assistant Professor of Biochemistry & Molecular Biology at Penn State University, USA).


Simultaneous DNA and RNA profiling in a case of sexual assault in a 3-year-old child: Forensic genetics solves the crime.
DNA profiling can identify an individual from a sample of biological material but it does not reveal what body fluid or tissue source the DNA profile originated from. In many cases it is important to know from what body fluid or tissue the DNA profile originated in order to provide crucial information necessary to the investigation, especially in cases where the victims are not able to give information about the dynamics of the event. For this purpose messenger RNA (mRNA) analysis has been shown to be a suitable method for the identification of body fluids, resulting in a trend to overcome the conventional approaches. Here we present the first report about case regarding a three-year-old child supposedly victim of a sexual assault with digital penetration. Thanks to the use of the combined DNA profiling and RNA analysis it was possible to demonstrate the sexual assault suffered by the victim.


Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone.
Dapsone (4,4'-diaminodiphenylsulfone) is an antimicrobial substance that also has anti-inflammatory activity, which has been attributed to inhibition of the leukocyte enzyme myeloperoxidase (MPO). We observed that dapsone was a much better inhibitor of the eosinophil peroxidase (EPO) in an assay that measured peroxidase-catalyzed oxidation of tetramethylbenzidine at pH 5.4. To clarify the specificity and pH-dependence of dapsone inhibition of the purified enzymes under more physiologic conditions, we studied peroxidase-catalyzed oxidation of chloride to the antimicrobial and cytotoxic agent hypochlorous acid. Taurine was added as a trap for hypochlorous acid, to prevent inactivation of the enzymes or chlorination of dapsone by hypochlorous acid. Dapsone was much more effective as an inhibitor of both MPO and EPO when chloride rather than tetramethylbenzidine was the substrate. Inhibition of both enzymes was greater at neutral pH than at acid pH (pH 7 vs pH 5), but EPO was more sensitive to inhibition than MPO regardless of pH. Inhibition was increased by lowering chloride, raising hydrogen peroxide, or lowering the enzyme concentration. Inhibition was accompanied by irreversible loss of enzyme activity, which was correlated with loss of the heme absorption spectrum, indicating chemical modification of the enzyme active site. EPO, but not MPO, was partially protected against inactivation by adding physiologic levels of bromide along with chloride. The results suggest that dapsone could prevent MPO- and EPO-mediated tissue injury at sites where the peroxidase enzymes are secreted and diluted into the neutral pH environment of the tissue interstitial space. Dapsone might not inhibit peroxidase-mediated antimicrobial activity, which occurs at high enzyme concentrations in the acid environment of phagolysosomes.


Carbamazepine up-regulates the binding of [3H]PK 11195 to platelets of epileptic patients.
The maximal number of binding sites (Bmax) and the equilibrium dissociation constant (KD) values for [3H]PK 11195 binding were determined in the platelet membranes of epileptic patients before and after 4 weeks of carbamazepine (CBZ) treatment, as well as in healthy controls. There was a decrease of 17.1% in the Bmax value of patients before treatment as compared to the controls whereas an increase of 50.3% was observed in CBZ-treated patients as compared to their pretreatment values. The up-regulatory effect of CBZ on peripheral benzodiazepine receptors was not accompanied by alterations in KD values.


Validation of the translation and cross-cultural adaptation into Spanish of the Postoperative Nausea and Vomiting Intensity Scale.
Postoperative nausea and vomiting (PONV) is a common problem in patients undergoing surgical procedures, generating patient dissatisfaction and increasing hospital costs. The Postoperative Nausea and Vomiting Intensity Scale identifies clinically significant cases; however, it has not been validated in Spanish. To carry out a cross-cultural adaptation of the PONV Intensity Scale into Spanish and validate it for use in the postoperative period of patients undergoing elective non-cardiac and non-intracranial surgery. Cross-sectional validation study of a diagnostic test. The NVPO Intensity Scale was culturally adapted to Spanish and administered to 393 adult hospitalized patients at 6 postoperative hours. The data were compared with the Apfel Scale and nausea measured on a visual analogue scale (VAS). Internal consistency and inter-observer concordance were calculated. 59.8% of patients presented NVPO, of which 14.5% were clinically significant. An acceptable internal consistency was obtained for the NVPO Intensity Scale (Cronbach's alpha 0.7) and a high inter-observer correlation (Kappa 0.9, 95% CI 0.86-0.92), statistically significant, for the overall scale. The correlation with VAS was high (Rho Spearman 0.9). The mean VAS and Apfel scale score was significantly higher in patients with clinically significant PONV. The PONV Intensity Scale adapted to Spanish is a valid and reliable instrument for monitoring and evaluating postoperative nausea and vomiting.


Primary 3D Culture of Human Thyroid Follicle-Like Structures in Platelet Lysate-Based Gel.
The results of 3D culturing of human thyroid follicle-like structures in a gel based on platelet lysate at the gel-air interface are presented. During culturing up to 4 months, no new follicle-like structures were formed and none were destroyed. During the first 2 months, most follicle-like structures increased in size; then, their grown decelerated, but they retained viability. Ki-67+ cells were observed in the majority of follicle-like structures. Most of them produced thyroglobulin. Follicle-like structures get closer, the number of contacts between them increased, and cluster appeared. Thus, the developed 3D culturing system in a gel based on platelet lysate is an adequate approach for maintaining structure and functional activity of human follicle-like structures in vitro for at least 2 months.


Immunoglobulin G4-Related Kidney Disease: A Comprehensive Pictorial Review of the Imaging Spectrum, Mimickers, and Clinicopathological Characteristics.
Immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) has recently been demonstrated to be an important part of IgG4-related sclerosing disease (IgG4-SD). However, since IgG4-KD is still relatively unfamiliar to radiologists and physicians as compared to IgG4-SD involving other organs, it could, therefore, be easily missed. In this article, we present a comprehensive pictorial review of IgG4-KD with regards to the imaging spectrum, mimickers, and clinicopathologic characteristics, based on our clinical experience with 48 patients during the past 13 years, as well as a literature review. Awareness of the broad imaging spectrum of IgG4-KD and differential diagnosis from its mimickers will thus facilitate its early diagnosis and treatment.


Dietary management of patients with diabetes treated by hemodialysis.
Early experience with the treatment of patients with insulin-dependent diabetes and renal failure by chronic hemodialysis indicated a high mortality and increased incidence of medical complications. Since 1972, a marked improvement in survival and reduction in incidence of complications has been attributed to more rigorous control of fluid overload, hypertension, and blood sugar levels by insulin therapy and careful dietary management. A diet has been developed which combines the diet used by dialysis patients with suitable modifications for the insulin-dependent patient with diabetes. The importance of patient education is stressed in an attempt to improve patient compliance.


Tracking live cell response to cadmium (II) concentrations by scanning electrochemical microscopy.
The biological chemistry of toxic heavy metals, such as Cd (II), has become an active area of research due to connections with increased oxidative stress, cytotoxicity, and human/animal carcinogenicity. In this study, scanning electrochemical microscopy (SECM) was used as a noninvasive technique to monitor membrane permeability of single live human bladder cancer cells (T24) subjected to exposure of Cd (II) at various concentrations. The addition of a membrane permeable redox mediator, ferrocenemethanol (FcMeOH), in combination with depth scan imaging provided probe approach curves (PACs) to reveal changes in membrane homeostasis. To demonstrate the strength of SECM as a bioanalytical technique for cell physiology and pathology, we tested responses of live cells after 1h incubations with various concentrations of Cd (II). For the first time, a trend in membrane permeability of Cd (II) treated live T24 cells was discovered. Dependent on the incubation concentration, the trend displayed an initial decrease in membrane permeability coefficient from 75μm/s for control cells to 25μm/s for cells incubated with 75μM Cd (II). This was followed by an eventual return to the permeability coefficient of control cells (75μm/s) with further increases in Cd (II) exposure. The cells were found to respond at as little as 10μM Cd (II) concentrations. This work further demonstrates the use of SECM as a bioanalytical technique to monitor cell physiology and topography. A greater insight into the complex mechanisms behind Cd (II) toxicity is anticipated.


CSF diazepam binding inhibitor and schizophrenia: clinical and biochemical relationships.
Diazepam-binding inhibitor (DBI) is a 9-kD neuropeptide that interacts with the benzodiazepine (BZD) binding sites of the neuronal gamma-aminobutyric acid type A (GABAA) receptor and with the glial mitochondrial BZD receptor (MBR). We explored the involvement of CSF DBI-LI in schizophrenia, based on the potential role of GABA in the negative symptoms associated with schizophrenia, the relationship of its receptors with dopamine and norepinephrine release, and the proposed therapeutic efficacy of BZDs in schizophrenia. Clinical data, CSF DBI-LI and CSF monoamine measures were obtained in 65 drug-free male chronic (DSM-IIIR) schizophrenic patients, 53 of whom were also tested prior to haloperidol withdrawal. Following haloperidol withdrawal, CSF DBI-LI increased significantly. Drug-free CSF DBI-LI did not correlate with CSF monoamines. CSF DBI-LI was significantly higher in paranoid compared to chronic undifferentiated schizophrenic patients. The data suggest that DBI may have a symptom modulatory rather than an etiological role in schizophrenia.


Anti-proliferative effect of pyridinolcarbamate and of aspirin in the early stages of atherogenesis in swine.
When young swine are fed a suitable hyperlipidemic (HL) diet the number of cells in intimal cell masses (ICM) of large and medium-sized arteries begins to increase in number; by 90 days on the diet the cell increase is several-fold compared to no significant increase in cell numbers in ICM of mash-fed controls. The objective of the current study was to see if the cell increase associated with the HL diet could be reduced by pyridinolcarbamate or aspirin. Arteries studied were the abdominal aorta and the coronaries; time on HL diet was 90 days. Both drugs resulted in significant reductions in the increases in cells in ICM associated with the HL diet in both of the arterial beds that were studied. The reduction was most prominent in the abdominal aorta where the increase in ICM cells in the untreated HL diet-fed swine was from an average of 242 +/- 50 cells per cross-section in the mash-fed controls to 1925 +/- 556; in the pyridinolcarbamate-treated swine the increase was only to 641 +/- 214 and in the aspirin-treated group to 770 +/- 146.


Structure of whey protein hydrolysate used as emulsifier in wet and dried oil delivery systems: Effect of pH and drying processing.
The secondary structure of whey protein concentrate hydrolysate (WPCH), used as an emulsifier in oil delivery systems, was investigated using Synchrotron Radiation Circular Dichroism (SRCD). The effect of pH on the conformation of peptides in solution and adsorbed at the oil/water interface, as well as the thermal stability of the systems was studied. Furthermore, oil-loaded microcapsules were produced by spray-drying or electrospraying to investigate the influence of encapsulating agents (glucose syrup, maltodextrin) and drying technique on the secondary structure of WPCH at the oil/water interface. Enzymatic hydrolysis resulted in peptides with a highly unordered structure (∼60% turns and unordered regions) in solution. However, WPCH adsorption onto the oil/water interface increased the α-helical content resulting in an improved thermal stability. The encapsulating agents and spray-drying process did not modify the conformation of WPCH at the oil/water interface. Nonetheless, electrospraying affected the SRCD spectra obtained for WPCH adsorbed at the oil/water interface.


Spraying tick-infested houses with lambda-cyhalothrin reduces the incidence of tick-borne relapsing fever in children under five years old.
Tick-borne relapsing fever (TBRF) is a major cause of morbidity and mortality of children in central Tanzania. This study assessed the effect of house interior residual spraying with lambda-cyhalothrin on domestic tick infestation and the incidence of TBRF in children under 5 years old. Two neighbouring villages were studied: one was sprayed with insecticide, the other left untreated. Samples of earth from the floors of 50 houses before and after spraying, and 50 houses in the control village, were sieved and ticks counted. The incidence of TBRF was estimated by microscopy of thick blood films taken from all children under 5 years old presenting with fever to the village dispensary or health workers. After 2 cycles of spraying, no tick was found in the treated houses; in the controls, tick numbers remained high. In the treated village there were 29 cases of TBRF among the 960 children under 5 years old in the 4 months before spraying, and one in the 4 months after spraying. In the control village there were 10 and 4 cases in the same periods among the 510 children. There was a significant reduction of 0.09 in the odds ratio of infection after spraying (95% confidence interval 0.01-0.87).


Relapsing pancreatitis associated with duodenal wall cysts. Diagnostic approach and treatment.
A case of enterogenous cysts of the duodenum in a 44-yr-old man complicated by duodenal obstruction and relapsing pancreatitis is presented. The cystic duodenal lesions were visualized by endoscopic retrograde cholangiopancreatography and for the first time by computed tomography and abdominal sonography. Thus, the diagnosis was made preoperatively. The cysts were excised successfully during a Whipple procedure. Awareness of this rare condition combined with modern x-ray, sonographic, and endoscopic techniques permit accurate preoperative diagnosis.


Effect of ketamine on local cerebral glucose utilization in fetal sheep.
Ketamine hydrochloride was infused intravenously in eight near-term fetal sheep, in doses ranging from 4.6 to 62.2 mg/kg. Local cerebral glucose utilization was determined by the [14C]deoxyglucose method. Heterogeneity in density of autoradiographs, a prominent feature in untreated fetal brains, was greatly diminished in animals receiving greater than 18 mg/kg, with differences between cerebral cortical gray and white matter virtually disappearing at high doses. In striking contrast to the pale, washed-out appearance in autoradiographs of most cerebral, cerebellar, and brain stem structures was a relatively high density of entorhinal cortex, hippocampus, lateral olfactory tract, and olfactory bulbs. Local cerebral glucose utilization of most gray and white matter structures was elevated in one ketamine-treated fetus experiencing a marked drop in PO2 during the study.


'Lady Windermere's counterpart? Pulmonary nontuberculous mycobacteria in men with bronchiectasis.
Pulmonary nontuberculous mycobacterial (NTM) disease occurs frequently in older women, and phenotypes of men with NTM disease are largely undescribed. We conducted a case-control study of 34 men with non-cystic fibrosis pulmonary NTM disease (cases), and three male and female control groups with or without NTM disease. Cases were median 71 years of age (range 30-94) and mostly non-Hispanic white (85.3%). These men had similarly low BMI as their female NTM patient counterparts, which was lower than both healthy men (p < 0.001) and bronchiectatic men without NTM (p = 0.06). Kyphoscoliosis was also more common in cases than healthy men (p= 0.007) or bronchiectatic men without NTM (p = 0.02). Our study was the first study to our knowledge to examine demographic features and phenotypes of men with NTM disease. Larger studies are needed to ascertain whether these phenotypes are characteristic of men with NTM disease.


Short-term microbial effects on n-alkane during the early phase degradation and consequential modification of biomarkers in a lowland subtropical rainforest in southern Taiwan: A litterbag experiment.
Accurate reconstructions of past environments are critical and urgent because they can help understand how modern environments might respond to current climatic and land-use changes. However, the effect of microbial degradation and consequential modification in plant-derived-biomarkers during the early degradation phase is not yet apparent, that might bias the paleoenvironmental investigation. In this regard, a litterbag experiment was conducted to reveal the microbial effects on n-alkane-associated biomarker changes associated with three habitats (ravine, windward, and leeward) in a lowland subtropical rainforest in southern Taiwan. Freshly collected leaves of plant species Iles rotunda, Ficus benjamina, and Castanopsis carlesii were distributed in the habitat leaf litterbag experiment for 15 and 75 days incubation, respectively. The results revealed that the average leaf decomposition rate was 19.4% ± 6.4% during the first 15 days and 39% ± 11% within 75 days incubation for all leaves. The overall leaf mass degradation of I. rotunda, F. benjamina and C. carlesii in the ravine after 75 days was 58%, 51% and 41%, respectively, which were higher than those in the windward (28%, 36% and 38%) and leeward habitats (35%, 26% and 42%, respectively) indicating higher decomposition rate in the ravine habitat than the others. The predominant n-alkanes in I. rotunda were C31 and C29, whereas in F. benjamina these were C31, C29, and C33, and in C. carlesii it was C31. After 75 days, the ravine habitat showed a 60% decrease in the total n-alkane concentration compared to windward and leeward habitats, suggesting the microbial community associated with the ravine habitat has a higher efficiency of degrading n-alkanes. However, the biomarkers such as carbon preference index (CPI), average carbon length (ACL) and the C31/C29 ratio did not show statistical difference in all habitats from 15 to 75 days incubation. The next-generation sequencing revealed that microbial communities changed significantly from 15 to 75 days in all habitats. The alkB gene-containing bacteria and their family lineages increased substantially during the first 15 days incubation in all habitats. Furthermore, several bacterial genera were exclusively present in the ravine habitat, whereas some were only in the leeward and windward habitats. Despite the heterogeneity of microbial proliferation, difference in biomass and n-alkane degradation among the three habitats, most of the n-alkane-associated biomarkers remained the same. Therefore, we concluded that the microbial effects on n-alkane degradation during the early phase in plant leaves had little influence on the results of most n-alkane biomarkers.


Styles of adjustment to coronary graft surgery.
Using Herzlich's descriptions of styles of adaptation to illness a conceptual scheme is offered which sets out four potential modes of adjustment to illness (ACCOMMODATION, ACTIVE-DENIAL, RESIGNATION, SECONDARY GAIN). A study is reported in which a group of 40 patients attending for CABGS were interviewed to assess their adjustment style, their expectations of surgery and their pattern of activities. A second group of 40 patients who had received CABGS approx. 11 months previously were also interviewed regarding their course of recovery, activity pattern and style of adjustment to illness. Results indicate that the same adjustment styles may not be employed prior to surgery as are adopted during recovery. Specific findings indicate that different styles of adjustment are consistent with different expectations of surgery; with changes in patterns of activity; and with particular courses of recovery. These differences were not explicable in terms of the degree of angina reported by patients either prior to or following CABGS. Discussion of these and related findings point to the explanatory potential of the conceptual system outlined in the paper, within which scheme further questions of adjustment to illness can be addressed.


The cosubstrate NADP(H) protects lysine 601 in the porcine NADPH-cytochrome P-450 reductase against pyridoxylation.
Lys601 in NADPH-cytochrome P-450 reductase is modified by reductive alkylation with pyridoxal 5'-phosphate (pyridoxylation). Lys601 is protected against modification by the cosubstrate NADP(H).


Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.
Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. NCT01373892.


Limiting intrusion-social control of outsiders in a healing community: an illustration of qualitative comparative analysis.
The analytic shceme of "limiting intrusion" was generated in this study, using research strategies that involved direct contact with subjects under natural living conditions. Data were collected in an experimental treatment community for diagnosed schizophrenics, where conventional psychiatric control structures are muted and denied. Approximately 200 hours of field observation, in-depth interviews with staff members, and documents related to the setting formed the data base. Qualitative comparative analysis is presented in detail to emphasize its relevance to theory building in nursing science.


TSLP: from allergy to cancer.
The cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers. While the role of TSLP in type 2 immune responses has been investigated extensively, recent studies have found an expanding role for TSLP in inflammatory diseases and cancer. In this Review, we will highlight major recent advances in TSLP biology, along with results from emerging clinical trials of anti-TSLP agents used for the treatment of a variety of inflammatory conditions.


Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study.
The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC). This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance. In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators. Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients' clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG). Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.


Architecture of the pontin/reptin complex, essential in the assembly of several macromolecular complexes.
Pontin and reptin belong to the AAA+ family, and they are essential for the structural integrity and catalytic activity of several chromatin remodeling complexes. They are also indispensable for the assembly of several ribonucleoprotein complexes, including telomerase. Here, we propose a structural model of the yeast pontin/reptin complex based on a cryo-electron microscopy reconstruction at 13 A. Pontin/reptin hetero-dodecamers were purified from in vivo assembled complexes forming a double ring. Two rings interact through flexible domains projecting from each hexamer, constituting an atypical asymmetric form of oligomerization. These flexible domains and the AAA+ cores reveal significant conformational changes when compared with the crystal structure of human pontin that generate enlarged channels. This structure of endogenously assembled pontin/reptin complexes is different than previously described structures, suggesting that pontin and reptin could acquire distinct structural states to regulate their broad functions as molecular motors and scaffolds for nucleic acids and proteins.


Helical (spiral) CT of the female pelvis.
Helical CT is well suited for evaluation of the female pelvis. The advantages of peak contrast enhancement and data continuity provide a major advance over conventional CT. Helical CT provides improved detection and characterization of gynecologic pathology and is recommended for the primary staging of gynecologic malignancy.


Evaluation of the validity and reliability of the KFORCE Sens® electrogoniometer in evaluation of wrist proprioception.
The aim of this study was to determine the validity and reliability of the KFORCE Sens® electrogoniometer in the evaluation of wrist proprioception. Wrist position sense was assessed on a Baseline® 360° universal goniometer and a KFORCE Sens® device. The validity and reliability of the KFORCE Sens® device for wrist position sense evaluation were investigated by comparing the two data sets. Fifty-three healthy volunteers (39 female, 14 male) with a mean age of 22.83 ± 1.28 years (range, 21-27 years) were included. Joint position sense test-retest reliability (intra-class correlation coefficient) on KFORCE Sens® was "very good" for all wrist movements. There was a very strong correlation between flexion-extension movements on the dominant side (r = 0.955), and a strong correlation between ulnar-radial deviation movements (r = 0.745). There was also a very strong (r = 0.863) correlation between flexion-extension movements on the non-dominant side and a strong correlation (r = 0.690) between ulnar-radial deviation movements (p < 0.05). Our results showed that the KFORCE Sens® device was a valid and reliable evaluation means of assessing wrist position sense.


Reduced syntactic recursion in spontaneous speech of Parkinson's disease patients.
Although characterized as a movement disorder, Parkinson's disease (PD) affects more than just the motor system. Within the heterogenous non-motor symptoms, language impairment is frequent but poorly understood beyond semantic processing. This study investigates the impact of PD on syntactic subordination in spontaneous language production. Fifteen PD patients in ON levodopa status narrated a short story guided by a set of pictures. Thirteen PD patients were also assessed in OFF levodopa status. Narrations were digitally recorded, subsequently transcribed and annotated, making the produced speech accessible to systematical quantitative analysis. Compared to a healthy matched control group, PD patients showed a significant reduction of subordinating structures while the number of non-embedding sentences remained unaffected. No significant effect comparing ON versus OFF levodopa status emerged. Our results suggest a contribution of the basal ganglia to language processing, such as syntactic composition, which, however, does not seem to be dopamine dependent.


Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis.
Various therapies are used for inflammatory bowel diseases (IBD), though none seem to be extremely effective. AP-1 is a major transcription factor that upregulates genes involved in immune and proinflammatory responses. We investigated decoy oligodeoxynucleotide (ODN) targeting AP-1 to prevent dextran sulfate sodium (DSS)-induced colitis in mice. Functional efficacies of synthetic decoy and scrambled ODNs were evaluated in vitro by a reporter gene luciferase assay and measuring flagellin-induced IL-8 expression by HCT-15 cells transfected with ODNs. Experimental colitis was induced in mice with a 2.5% DSS solution in drinking water for 7 days, and decoy or scrambled ODNs were intraperitoneally injected from days 2 to 5. Colitis was assessed by weight loss, colon length, histopathology, and detection of myeloperoxidase (MPO), IL-1beta, and TNF-alpha in colon tissue. Therapeutic effects of AP-1 and NF-kappaB decoy ODNs were compared. Transfection of AP-1 decoy ODN inhibited AP-1 transcriptional activity in reporter assays and flagellin-induced IL-8 production in vitro. In mice, AP-1 decoy ODN, but not scrambled ODN, significantly inhibited weight loss, colon shortening, and histological inflammation induced by DSS. Further, AP-1 decoy ODN decreased MPO, IL-1beta, and TNF-alpha in colonic tissue of mice with DSS-induced colitis. The AP-1 decoy therapeutic effect was comparable to that of NF-kappaB decoy ODN, which also significantly decreased intestinal inflammation. Double-strand decoy ODN targeting AP-1 effectively attenuated intestinal inflammation associated with experimental colitis in mice, indicating the potential of targeting proinflammatory transcription factors in new therapies for IBD.


Immunofluorescent studies in ocular cicatricial pemphigoid.
Twenty nine patients with cicatrizing conjunctivitis were studied; 17 with a clinical diagnosis of cicatricial pemphigoid, five with a clinical diagnosis of pseudopemphigoid caused by long-term application of topical medication and seven who had a cicatrizing conjunctivitis from other causes. Biopsies from clinically uninvolved bulbar conjunctiva were taken for direct immunofluorescence and blood was taken for indirect immunofluorescence using normal human conjunctiva, oral mucosa and skin as substrates. On direct immunofluorescence, in vivo bound immunoglobulins were found along the basement membrane in 10 of the 17 patients with cicatricial pemphigoid, one of the five with pseudopemphigoid and two of the seven with a cicatrizing conjunctivitis associated with other diseases. Circulating anti-basement membrane zone antibodies were found only when conjunctiva was used as a substrate. These were present in seven of the patients with cicatricial pemphigoid, three of those with pseudopemphigoid and two of those with a cicatrizing conjunctivitis caused by other diseases. These results indicate that direct immunofluorescence is a useful, but not absolute diagnostic marker for ocular cicatricial pemphigoid. The results in the pseudopemphigoid group argue that this is an immunologically mediated disorder indistinguishable from spontaneous cicatricial pemphigoid and probably triggered by the drugs. The presence of circulating antibodies should allow for precise identification of the antigen involved in cicatricial pemphigoid using SDS electrophoresis and Western blot analysis.


Ischemia as a potential etiologic factor in idiopathic unilateral sudden sensorineural hearing loss: Analysis of posterior circulation arteries.
The association between idiopathic sudden sensorineural hearing loss (ISSNHL) and the radiologic characteristics of the vertebrobasilar artery is unclear. We hypothesized that the degree and direction of vertebrobasilar artery curvature in the posterior circulation contribute to the occurrence of ISSNHL. We consecutively enrolled patients diagnosed with unilateral ISSNHL in two tertiary hospitals. Magnetic resonance images were performed in all patients to exclude specific causes of ISSNHL, such as vestibular schwannoma, chronic mastoiditis, and anterior inferior cerebellar artery infarct. We measured the following parameters of posterior circulation: vertebral and basilar artery diameter, the degree of basilar artery curvature (modified smoker criteria), and vertebral artery dominance. Pure tone audiometries were performed at admission and again 1 week and 3 months later. A total of 121 ISSNHL patients (mean age, 46.0 ± 17.3 years; 48.8% male) were included in these analyses. The proportion of patients with the left side hearing loss was larger than the proportion with the right side hearing loss (left, 57.9%; right, 42.1%). The majority of patients were characterized by a left dominant vertebral artery and right-sided basilar artery curvature. The direction of the basilar artery curvature was significantly associated with hearing loss lateralization (p = 0.036). Age and sex matched multivariable analyses revealed the absence of diabetes and right-sided basilar artery curvature as significant predictors for left sided hearing loss. There was no statistical difference between atherosclerotic cardiovascular risk score (high versus low) and hearing outcomes at 3 months. In ISSNHL, the laterality of hearing loss was inversely associated with the direction of basilar artery curvature. Our results, therefore, indicate the importance of vascular assessment when evaluating ISSNHL.


Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl-hydrazone derivatives as histone lysine acetyl-transferase inhibitors and apoptosis inducers.
Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol-2-yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti-histone lysine acetyl-transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A-associated protein p300), compared to CPTH2. Among all the tested derivatives, compound 10b revealed the highest activity against both P300 and pCAF. In addition, the new hits were tested for anticancer efficacy against two leukemia cell lines. Most of them showed a moderate to potent antitumor effect on the k562 and CCRF-CEM cell lines. Interestingly, the activity of compound 10b against the k562 cell line was found to be higher than that of CPTH2. Furthermore, it showed a good safety profile, better than CPTH2 on normal cells. Molecular docking analysis was carried out to reveal the crucial binding contacts in the inhibition of the P300 and pCAF enzymes.


Granulomas of intestinal tuberculosis and Crohn's disease can be differentiated by CD73 cell surface marker expression: a pilot study.
Intestinal tuberculosis (ITB) and Crohn's disease are similar granulomatous disorders. Granulomas are present in both and difficult to differentiate on histopathology alone. A recent study demonstrated recruitment of mesenchymal cells (MSCs) at the periphery of granulomas in lymph node tuberculosis which suppressed T cell responses. We hypothesized that granulomas of ITB would also recruit MSCs to evade host immune response. The purpose of this study was to demonstrate MSC markers in granulomas of ITB and evaluate whether distribution of MSC markers could differentiate between granulomas of Crohn's and ITB. We initially retrospectively enrolled 17 patients with confirmed ITB (8) or Crohn's (9) with granulomas on histopathology. Tissues were evaluated by immunofluorescence for MSC markers CD29, CD90, CD73 and absence of haematopoietic markers CD31, CD34, CD45 and CD14. Double-staining was done to confirm presence of MSCs. Subsequently, 23 postoperative specimens of Crohn's (18) and ITB (5) were analyzed for validation. Overall, 27 Crohn's and 13 ITB cases were assessed. CD29 and CD90 positive cells were noted around both ITB and Crohn's granulomas. MSC marker CD73 was expressed around the granulomas of ITB alone and was completely absent in the Crohn's. The subsequent assessment of granulomas in postoperative specimens of Crohn's and ITB also showed similar results. Granulomas of ITB and Crohn's disease can be differentiated by CD73 MSC surface marker expression. The differential CD73 expression around ITB granuloma indicates that Mycobacterium tuberculosis evades host immunity by recruiting MSCs with CD73 expression. MSCs with increased CD73 expression could be the future for therapeutic intervention in Crohn's.


Social Disadvantage, Politics, and Severe Acute Respiratory Syndrome Coronavirus 2 Trends: A County-level Analysis of United States Data.
Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence. We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June-30 June 2020 and social, demographic, and political characteristics of the county. Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24-72]) than counties with nonincreasing case counts (median, 40 [IQR, 19-66]; P = .009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000-1 million population (P < .001), to have a higher percentage of black residents (9% vs 6%; P = .013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P = .044). In the multivariable model, metropolitan areas of 250 000-1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts. Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control.


Current approach to seronegative myasthenia.
The group of patients with weakness or fatigue who have electrophysiological evidence of neuromuscular transmission defects, but no antibodies against either acetyl choline receptor or muscle specific kinase, need special evaluation and therapeutic consideration. Such seronegative patients may have low affinity antibodies but may also be late onset of a congenital myasthenic syndrome. This review discuss the practical approach toward the condition of seronegative myasthenia.


A global goodness-of-fit test for receiver operating characteristic curve analysis via the bootstrap method.
Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap. A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported. In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC=0.888; p=0.78, and AUC=0.888; p=0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC=0.898; p=0.61, and AUC=0.899; p=0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC=0.766; p=0.004, and AUC=0.831; p=0.03), respectively. In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.


Metformin and Trehalose-Modulated Autophagy Exerts a Neurotherapeutic Effect on Parkinson's Disease.
Since the number of aged people will increase in the next years, neurodegenerative diseases, including Parkinson's Disease (PD), will also rise. Recently, we demonstrated that autophagy stimulation with rapamycin decreases dopaminergic neuronal death mediated by oxidative stress in the paraquat (PQ)-induced PD model. Assessing the neurotherapeutic efficacy of autophagy-inducing molecules is critical for preventing or delaying neurodegeneration. Therefore, we evaluated the autophagy inducers metformin and trehalose effect in a PD model. Autophagy induced by both molecules was confirmed in the SH-SY5Y dopaminergic cells by detecting increased LC3-II marker and autophagosome number compared to the control by western blot and transmission electron microscopy. Both autophagy inducers showed an antioxidant effect, improved mitochondrial activity, and decreased dopaminergic cell death induced by PQ. Next, we evaluated the effect of both inducers in vivo. C57BL6 mice were pretreated with metformin or trehalose before PQ administration. Cognitive and motor deteriorated functions in the PD model were evaluated through the nest building and the gait tests and were prevented by metformin and trehalose. Both autophagy inducers significantly reduced the dopaminergic neuronal loss, astrocytosis, and microgliosis induced by PQ. Also, cell death mediated by PQ was prevented by metformin and trehalose, assessed by TUNEL assay. Metformin and trehalose induced autophagy through AMPK phosphorylation and decreased α-synuclein accumulation. Therefore, metformin and trehalose are promising neurotherapeutic autophagy inducers with great potential for treating neurodegenerative diseases such as PD.


Randomised controlled trial to evaluate a new double-layer air-cell overlay for elderly patients requiring head elevation.
A clinical investigation was conducted concerning the effects of a newly designed double-layer air-cell overlay in preventing the onset of pressure ulcers for patients with a Braden scale score of < or = 16, and who require a head-elevated position of 45 degrees or higher. A randomised controlled trial was undertaken involving 82 patients from a general hospital ward using one of the following three support surfaces: a double-layer air-cell overlay, a single-layer air-cell overlay or a standard hospital mattress. A significantly lower percentage of patients using the double-layer air-cell overlay developed pressure ulcers (3.4%) compared to 19.2% and 37.0% for those patients using the single-layer air-cell overlay and standard mattress respectively. Based on these findings, a double-layer air-cell overlay should be more effective in preventing the onset of pressure ulcers than either a single-layer air-cell overlay or a standard hospital mattress for subjects requiring head elevation.


Cytotoxic effects of adriamycin on mouse hypoglossal neurons following retrograde axonal transport from the tongue.
We reported recently that the fluorescent, cytostatic drug, adriamycin (Doxorubicin) may reach the hypoglossal neurons by retrograde axonal transport from the nerve terminals of the tongue. The present investigation was undertaken to ascertain whether morphological changes occur in the hypoglossal neurons due to retrograde transport of adriamycin. Neuronal degeneration was observed in the hypoglossal nucleus 14 days after i.m. injection of adriamycin into the tongue. Early neuronal changes, such as rarefaction of the nuclear chromatin and segregation and fragmentation of the nucleolar components, were succeeded by cytoplasmic vacuolation, disappearance of ribosomes and other degenerative features. These observations are important from a neurotoxicologic viewpoint since they demonstrate that retrograde axonal transport may provide a route for the entry of adriamycin into the nervous system. Thus far, adriamycin appears to be the only known substance which can be traced directly in the neurons and cause their degeneration. An experimental method of damaging the motor neurons of the CNS has been introduced. A new toxic model for the investigation of experimental motor neuron disease is therefore available by the use of adriamycin.


Recovery of walking speed and symmetrical movement of the pelvis and lower extremity joints after unilateral THA.
In 17 patients with unilateral hip disease who underwent total hip arthroplasty (THA), the gait was analyzed preoperatively and 1, 3, 6, and 12 months after unilateral THA using a Vicon system to assess the recovery of walking speed and symmetrical movement of the hip, knee, ankle, and pelvis. The walking speed of these patients reached that of normal Japanese persons by 12 months after surgery. Walking speed was correlated with the range of hip motion on the operated side at 1 month postoperatively, and was correlated with the hip joint extension moment of force on both sides from 3 to 6 months after surgery. Before THA, asymmetry was observed in the range of the hip motion, maximum hip flexion, maximum hip extension, maximum knee flexion, as well as in pelvic obliquity, pelvic tilt, and pelvic rotation. There were no differences of the stride length or step length between both sides throughout the observation period. The preoperative range of hip flexion on the operated side during a gait cycle (21.3+/-7.9 degrees ) was significantly smaller than on the non-operated side (46.7+/-7.1 degrees ), and the difference between sides was still significant at 12 months after surgery (35.1+/-6.2 degrees on the operated side and 43.6+/-5.7 degrees on the non-operated side). The majority (74%) of the difference in hip motion range during this period was due to the difference in maximum extension of the hip. The increase in the range of pelvic tilt and the range of motion of the opposite hip showed an inverse correlation with the range of motion of the operated hip, suggesting a compensatory preoperative role. However, this correlation became insignificant after 6 months postoperatively. Asymmetry of the range of hip motion persisted at 12 months after THA in patients with unilateral coxoarthropathy during free level walking, while the operation normalized the spatial asymmetry of other joints and the walking speed prior to the recovery of hip motion.


[Clinical examination of spatial neglect and other disorders of spatial cognition].
Neglect occurring after stroke, neoplasms or degenerative processes can lead to considerable disability in everyday life as can other disorders of spatial orientation. Therefore, a dedicated examination and early diagnostic classification are obligatory. Behavioral tests are helpful in this respect, enabling the clinician to obtain an initial overview of the existing deficits even at the patient's bedside. The clinical (bedside) examination of spatial neglect as well as the corresponding differential diagnostic procedure for the clarification of (possibly additionally or exclusively existing) hemianopia and extinction, as well as the examination of disorders of visuospatial perception, visuoconstructive disorders, topographic disorders, Bálint's syndrome, simultanagnosia, and optic ataxia are presented. The presentation is based on the newly revised (year 2023) guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) on this subject area.


Assessing the resilience of urban areas to traffic-related air pollution: Application in Greater Paris.
Recent studies report that outdoor air pollution will become the main environmental cause of premature death over the next few decades (OECD, 2012; WHO, 2014; World Bank, 2016). Cities are considered hot spots and urban populations are particularly exposed. There is therefore an urgent need to adapt urban systems and urban design to tackle this issue. While most European cities have introduced measures to reduce emissions, action is still required to reduce concentrations and exposure, and a holistic approach to urban design is badly needed. The concept of urban resilience, defined by Holling (1987) as the ability of a city to absorb a disturbance while maintaining its functions and structures, may offer a new paradigm for tackling urban air pollution. We propose to adapt the concept of urban resilience to outdoor air pollution. A method has been developed to assess the resilience of an urban area to outdoor air pollution. Three "resilience capacities" have been identified: the capacity of an urban area to decrease air pollution emissions, the capacity to decrease concentrations and the capacity to decrease exposure. The calculation is based on the analysis of urban design, defined as the pattern of buildings as well as the structural elements that define an urban area (urban morphology; transport network, services and land use). For each resilience capacity, indicators are calculated using a Geographic Information System (GIS) and a grid-based approach. This method has been implemented in the Greater Paris area within a 500m grid-cell system. Greater Paris is one of the densest urban areas in Europe and experiences high air pollution levels. The proposed "quick scan" method helps to localize areas where specific action is needed.


White blood cell differentials performance of a new automated digital cell morphology analyzer: Mindray MC-80.
The manual differential count has been recognized for its disadvantages, including large interobserver variability and labor intensiveness. In this light, automated digital cell morphology analyzers have been increasingly adopted in hematology laboratories for their robustness and convenience. This study aims to evaluate the white blood cell differential performance of the Mindray MC-80, the new automated digital cell morphology analyzer. The cell identification performance of Mindray MC-80 was evaluated for sensitivity and specificity using pre-classification and post-classification of each cell class. The method comparison study used manual differentials as the gold standard for calculating Pearson correlation, Passing-Bablok regression, and Bland-Altman analysis. In addition, the precision study was performed and evaluated. The precision was within the acceptable limit for all cell classes. Overall, the specificity of cell identification was higher than 95% for all cell classes. The sensitivity was greater for 95% for most cell classes, except for myelocytes (94.9%), metamyelocytes (90.9%), reactive lymphocytes (89.7%), and plasma cells (60%). Pre-classification and post-classification results correlated well with the manual differential results for all the cell types investigated. The regression coefficients were greater than 0.9 for most cell classes except for promyelocytes, metamyelocytes, basophils, and reactive lymphocytes. The performance of Mindray MC-80 for white blood cell differentials is reliable and seems to be acceptable even in abnormal samples. However, the sensitivity is less than 95% for certain abnormal cell types, so the user should be aware of this limitation where such cells are suspected.


Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.
Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management.


Reactor performance of a 750 m(3) anaerobic digestion plant: varied substrate input conditions impacting methanogenic community.
A 750 m(3) anaerobic digester was studied over a half year period including a shift from good reactor performance to a reduced one. Various abiotic parameters like volatile fatty acids (VFA) (formic-, acetic-, propionic-, (iso-)butyric-, (iso-)valeric-, lactic acid), total C, total N, NH4 -N, and total proteins, as well as the organic matter content and dry mass were determined. In addition several process parameters such as temperature, pH, retention time and input of substrate and the concentrations of CH4, H2, CO2 and H2S within the reactor were monitored continuously. The present study aimed at the investigation of the abundance of acetogens and total cell numbers and the microbial methanogenic community as derived from PCR-dHPLC analysis in order to put it into context with the determined abiotic parameters. An influence of substrate quantity on the efficiency of the anaerobic digestion process was found as well as a shift from a hydrogenotrophic in times of good reactor performance towards an acetoclastic dominated methanogenic community in times of reduced reactor performance. After the change in substrate conditions it took the methano-archaeal community about 5-6 weeks to be affected but then changes occurred quickly.


Multitensor approach for analysis and tracking of complex fiber configurations.
A multidiffusion-tensor model (MDT) is presented containing two anisotropic and one isotropic diffusion tensors. This approach has the ability to detect areas of fiber crossings and resolve the direction of crossing fibers. The mean diffusivity and the ratio of the tensor compartments were merged to one independent parameter by fitting MDT to the diffusion-weighted intensities of a two-point data acquisition scheme. By an F-test between the errors of the standard single diffusion tensor and the more complex MDT, fiber crossings were detected and the more accurate model was chosen voxel by voxel. The performance of crossing detection was compared with the spherical harmonics approach in simulations as well as in vivo. Similar results were found in both methods. The MDT model, however, did not only detect crossings but also yielded the single fiber directions. The FACT algorithm and a probabilistic connectivity algorithm were extended to support the MDT model. For example, a mean angular error smaller than 10 degrees was found for the MDT model in a simulated fiber crossing with an SNR of 80. By tracking the corticospinal tract the MDT-based tracks reached a significantly greater area of the gyrus precentralis.


Clinical Conditions "Suggestive of Progressive Supranuclear Palsy"-Diagnostic Performance.
The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level "suggestive of progressive supranuclear palsy" for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


High-Throughput DNA Array for SNP Detection of KRAS Gene Using a Centrifugal Microfluidic Device.
Here, we describe detection of single nucleotide polymorphism (SNP) in genomic DNA samples using a NanoBioArray (NBA) chip. Fast DNA hybridization is achieved in the chip when target DNAs are introduced to the surface-arrayed probes using centrifugal force. Gold nanoparticles (AuNPs) are used to assist SNP detection at room temperature. The parallel setting of sample introduction in the spiral channels of the NBA chip enables multiple analyses on many samples, resulting in a technique appropriate for high-throughput SNP detection. The experimental procedure, including chip fabrication, probe array printing, DNA amplification, hybridization, signal detection, and data analysis, is described in detail.


Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.
The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events. This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event. The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01-1.24) and 1.19 (1.07-1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07-2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46-3.61), using the Youden's index. Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.


The chemotherapy of advanced bladder cancer.
This paper traces the development of the use of chemotherapy in the management of advanced bladder carcinoma in Europe. A number of agents, including cisplatin, methotrexate, vinblastine, adriamycin, fluorouracil and cyclophosphamide, have been investigated singly and in combination in phase II studies, and it is envisaged that an ideal combination chemotherapy regimen giving lasting complete response will ultimately be used along with limited ablative surgery in the management of localised advanced bladder cancer. Careful application of the increasing knowledge of the biology of transitional cell carcinoma and strict adherence to rigid criteria of response in the assessment of new agents appears at last to offer hope of an improvement in the prognosis of invasive bladder cancer.


Interleukin-6 in neurons of the pterygopalatine ganglion of the rat.
An indirect immunofluorescence method was used to study the pterygopalatine nerve ganglion in rats with the aim of determining the identification and locations within it of neurons expressing IL-6. A low density of IL-6-immunoreactive cells was seen in the cranial area of the ganglion; the medial surface and caudal area contained occasional cells demonstrating nuclear fluorescence; rarer groups of cells, organized into chains, were seen in the intermediate part of the ganglion on its lateral margin contacting the maxillary nerve.


Physico-chemical characterization of a new salt of ibuprofen.
A new salt of ibuprofen was prepared by reaction with t-butylamine; its formation was confirmed by IR and 1H-NMR spectroscopy. The salt was characterized by thermoanalytical, X-ray powder diffraction and solubility studies. The salt was found to be 1.5 times more soluble in water than was ibuprofen, with an enthalpy of solution of -8.84 kcal mol-1.


Single lateral versus medial and lateral plates for treating displaced scapular body fractures: a retrospective comparative study.
This study compared the outcomes and complications of single lateral plating vs. dual plating for treating displaced scapular body fractures. Open reduction and internal fixation using locking plates was performed in 45 patients with displaced scapular fractures. A single lateral plate fixed in the lateral border was used in 22 patients (group A), and dual plates fixed in both the lateral and medial borders were used in 23 (group B). The average follow-up duration in both groups was 20 months. A remarkable difference was seen between the 2 groups in mean operative time and blood loss, although the Disabilities of the Arm, Shoulder and Hand and Constant Shoulder scores at the final follow-up were similar. The prominence rate of the hardware was 27.3% (6 of 22) in group A and 65.2% (15 of 23) in group B. The plate removal rate was 31.8% (7 of 22) in group A and 78.3% (18 of 23) in group B. Open reduction using a single plate on the lateral border for treating displaced scapular body fractures can lead to good functional outcomes, shorter operative time, less blood loss, and fewer plate-related complications compared with the dual-plating technique.


CaRdiac Arrest Survival Score (CRASS) - A tool to predict good neurological outcome after out-of-hospital cardiac arrest.
The aim of this study was to develop a score to predict the outcome for patients brought to hospital following out-of-hospital cardiac arrest (OHCA). All patients recorded in the German Resuscitation Registry (GRR) who suffered OHCA 2010-2017, who had ROSC or ongoing CPR at hospital admission were included. The study population was divided into development (2010-2016: 7985) and validation dataset (2017: 1806). Binary logistic regression analysis was used to derive the score. The probability of hospital discharge with good neurological outcome was defined as 1/(1 + e-X), where X is the weighted sum of independent variables. The following variables were found to have a significant positive (+) or negative (-) impact: age 61-70 years (-0·5), 71-80 (-0·9), 81-90 (-1·3) and > = 91 (-2·3); initial PEA (-0·9) and asystole (-1·4); presumable trauma (-1·1); mechanical CPR (-0·3); application of adrenalin > 0 - < 2 mg (-1·1), 2 - <4 mg (-1·6), 4 - < 6 mg (-2·1), 6 - < 8 mg (-2·5) and > = 8 mg (-2·8); pre emergency status without previous disease (+0·5) or minor disease (+0·2); location at nursing home (-0·6), working place/school (+0·7), doctor's office (+0·7) and public place (+0·3); application of amiodarone (+0·4); hospital admission with ongoing CPR (-1·9) or normotension (+0·4); witnessed arrest (+0·6); time from collapse until start CPR 2 - < 10 min (-0·3) and > = 10 min (-0·5); duration of CPR <5 min (+0·6). The AUC in the development dataset was 0·88 (95% CI 0·87-0·89) and in the validation dataset 0·88 (95% CI 0·86-0·90). The CaRdiac Arrest Survival Score (CRASS) represents a tool for calculating the probability of survival with good neurological function for patients brought to hospital following OHCA.


A large Q fever outbreak in the West Midlands: clinical aspects.
In the spring of 1989 the largest outbreak of acute Q fever recorded in the United Kingdom occurred in Solihull and surrounding areas of the West Midlands. The diagnosis was confirmed in 147 people, mainly males of working age. Windborne spread from farmland to the south of the urban area was the most likely route of infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed by weight loss reported by 83/101 (82%). Headache, often severe, was experienced by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102 (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%). Neurological features, seen in 23% of cases, were more prominent in this outbreak than is commonly recognized. Persisting ill health 6 months following the acute episode not due to chronic Q fever was also a prominent feature of this largely urban outbreak.


Differences in regional wash-in and wash-out time constants for xenon-CT ventilation studies.
Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO-WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon. WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO-WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI-WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh-Taylor instabilities set up at interfaces between two gases of different densities.


Squamous cell carcinoma of skin developing in a skin graft donor site.
We report a case of squamous cell carcinoma of the skin of the right ring finger which was treated by excision and split skin grafting. Three months later the patient presented with a further lesion at the margin of the skin graft donor site on the right thigh. Excision biopsy of this second lesion revealed a squamous cell carcinoma of a similar pathological appearance to the original lesion. We have been unable to trace any previous similar reports. A possible pathological basis for the sequence of events is discussed.


Detection of Toxoplasma gondii antibodies in captive non-human primates in the Amazon region, Brazil.
Toxoplasma gondii infections in captive non-human primates are of interest because often they die due to severe toxoplasmosis. Thus, we aimed to evaluate samples from a serum bank to T. gondii antibodies. Serum samples of 179 monkeys from the National Center of Primates, Brazil, were retrospective analyzed for T. gondii IgG antibodies by modified agglutination test using formalin-fixed whole parasites as antigen (cutoff 1:25). Among the 179 samples tested, 88 (49.2%) were positive. Twelve of the 18 evaluated species presented at least one positive animal. A higher occurrence of positive animals was found in New World (52.2%) than Old World (22.2%) monkeys (P = .023) and in the animals from domestic donation origin, which had lived in human homes as pets (P = .004). We confirm the widespread presence of T. gondii in captive monkeys and contribute to the range of species that can be infected by this parasite.


Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions.
Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.


ERα, microRNAs, and the epithelial-mesenchymal transition in breast cancer.
The most common form of breast cancer, luminal A, is estrogen receptor α (ERα)-positive and epithelial, but nevertheless can metastasize. The process of epithelial-mesenchymal transition (EMT) is probably the first step in the metastasis of epithelial cancers. We discuss the characteristics of EMT, including factors that induce EMT, and the relationship of EMT to cancer stem cells (CSCs). Estrogen/ERα signaling maintains an epithelial phenotype and suppresses EMT. An overview of microRNAs in breast cancer is presented, including how microRNA biogenesis is altered in cancer and regulated by ERα. We also discuss the role of the miR-200 family in opposing EMT. Finally, we discuss specific microRNAs that target ERα and regulate EMT in breast cancer, and the role of these microRNAs in breast cancer progression.


Estrogen receptor ligands. Part 14: application of novel antagonist side chains to existing platforms.
Two novel side chains which had previously been found to enhance antagonist activity in the dihydrobenzoxathiin SERM series were applied to three existing platforms. The novel side chains did not improve the antagonist activity of the existing platforms.


Matrix interference free determination of perchlorate in urine by ion association-ion chromatography-mass spectrometry.
Quantitative measurement of perchlorate in biological fluids is of importance to assess its toxicity and to study its effects on the thyroid gland. Whenever possible, urine samples are preferred in toxicologic/epidemiologic studies because sample collection is non-invasive. We present here a pretreatment method for the determination of perchlorate in urine samples that lead to a clean matrix. Urine samples, spiked with isotopically labeled perchlorate, are exposed to UV to destroy/decompose organic molecules and then sequentially treated with an H+-form cation exchange resin to remove protolyzable compounds, with ammonia to raise the pH to 10-11 and finally passed through a mini-column of basic alumina to remove the color and other organic matter. After filtration through a 0.45 microm syringe filter, the sample thus prepared can be directly injected into an ion chromatograph (IC). We use ion association-electrospray ionization-mass spectrometry (ESI-MS) to detect and quantify perchlorate. The proposed sample preparation method leads to excellent limits of detection (LOD's) for perchlorate since there is essentially no dilution of sample and the matrix effects are eliminated. Results of urine samples from both men and women volunteers are reported for perchlorate, as well as for iodide and thiocyanate, which are generally present at much higher concentrations and for which a "dilute and shoot" approach is adequate. The limit of detection (S/N=3) for iodide, thiocyanate and perchlorate by the present method was 0.40, 0.10 and 0.080 microg l(-1), respectively.


[Use of omental flap in the course of evolution of treated breast cancer. Apropos of 20 omental flaps done at the Gustave-Roussy Institute].
Some of the complications which occur after classical treatment of breast cancer can best be treated by use of the omental flap described by Kiricuta. These include radionecrosis of the chest wall, skin defects occuring after radical mastectomy combined with maximal irradiation, and local recurrence taking place after classical treatment. The results from the Gustave-Roussy Institute, which include experience with twenty omental flaps performed in breast cancer patients, confirm the exceptional qualities of this flap, especially reconstructing defects in irradiated tissue.


Unfolding, conformational change of active sites and inactivation of creatine kinase in SDS solutions.
It has been reported that inactivation occurs before noticeable conformational change can be detected during denaturation of creatine kinase (ATP: creatine N-phosphotransferase, EC 220.127.116.11) and other enzymes by guanidinium chloride or urea. Therefore, Tsou suggested that enzyme active sites may display more conformational flexibility than the enzyme molecules as a whole [Tsou (1986) Trends Biochem. Sci. 11, 427-429; Tsou (1993) Science 262, 380-381]. In this study, the conformational change of the active site, the unfolding of the whole molecule and the inactivation of creatine kinase in solutions of different concentrations of SDS are compared. The results show that, at low SDS concentrations, the conformational change of the active site and inactivation of the enzyme occur to nearly the same extent. However, both of these changes occur at much lower concentrations of SDS than required to significantly unfold the enzyme molecule. The rates of conformational changes of enzyme active sites are markedly faster than those of inactivation. However, at the same SDS concentration, both the inactivation rate and the rate of the active site conformational change are much faster than that of the unfolding of the enzyme molecule as a whole. The above results provide direct evidence of the flexibility of the active site of creatine kinase.


Extraosseous 99mTc-MDP uptake in squamous cell carcinoma of the pleura.
A rare case of squamous cell carcinoma of the pleura in association with tuberculosis is described. Concentration of 99mTc-methylenediphosphonate was demonstrated in the calcified pleural tumoral tissue. To the best of our knowledge, such concentration has not been previously reported. The possible etiological factors of this disease and findings are briefly discussed.


Insurance plan raises benefits, lowers costs.
The Direct Service Contract encourages hospital employees to use their own hospital for medical services. The plan benefits the hospital, cuts costs, and raises employee morale.