Promoter mutations that allow nifA-independent expression of the nitrogen fixation nifHDKY operon.
The nifHDKY operon of Klebsiella pneumoniae encodes for structural polypeptides of nitrogenase and requires the nifA gene product for transcription. Mutations that allow transcription of the nifHDKY operon in absence of the nifA gene product were characterized in plasmids containing the regulatory region of nifHDKY and nifH fused in phase to lacZ. beta-Galactosidase activity served as a measure for nifH expression. Most mutations were located in the nif regulatory region and included insertion sequence 2 (IS2) insertions, a sequence duplication, and a base substitution. In Escherichia coli, beta-galactosidase activity expressed from the mutant plasmids in the absence of nifA was 6-30% of the nifA-activated, parental level. Expression from most mutant plasmids was further increased by nifA. In K. pneumoniae, IS2-containing plasmids expressed low levels of beta-galactosidase and responded poorly, if at all, to activation by nifA, whereas expression from other mutant types was similar to that observed in E. coli. Nucleotide sequence analysis of two mutants indicated that sequences within 41 base pairs upstream to the nifH coding sequence were involved in nif-specific regulation. The results suggest that an inverted repeat element in this region, which could theoretically form a cruciform structure in the DNA, is involved in the transcriptional control of the nifHDKY operon.


Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.
We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.


[The role of mucolytic therapy in the treatment of sinobronchial syndrome].
The objective of the present study was to estimate the therapeutic efficacy and safety of myrtol standardized (gelomyrtol forte) and acetylcysteine given to 11 and 13 patients respectively presenting with sinobronchial syndrome. Dynamics of clinical and roentgenological signs and symptoms in these patients was investigated throughout the period of therapy. The best clinical results were obtained using myrtol standardized. Specifically, the summary score characterizing the change of clinical symptoms decreased from the initial value of 32 to 0.73 on the 7th day after the initiation of therapy and to 0.18 after its termination. The decrease of the same parameter in the group of the patients treated with acetylcysteine to 1.3 and 0.38 (mean score for the group) was documented on days 7 and 10 after the beginning of therapy respectively.


Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.
Tropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. There is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. One new approach is to apply host defense peptides (HDP; formerly called antimicrobial peptides) to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in their insect vectors. A potent anti-parasite effector is bovine myeloid antimicrobial peptide-27 (BMAP-27), a member of the cathelicidin family. Although BMAP-27 is a potent inhibitor of microbial growth, at higher concentrations it also exhibits cytotoxicity to mammalian cells. We tested the anti-parasite activity of BMAP-18, a truncated peptide that lacks the hydrophobic C-terminal sequence of the BMAP-27 parent molecule, an alteration that confers reduced toxicity to mammalian cells. BMAP-18 showed strong growth inhibitory activity against several species and life cycle stages of African trypanosomes, fish trypanosomes and Leishmania parasites in vitro. When compared to native BMAP-27, the truncated BMAP-18 peptide showed reduced cytotoxicity on a wide variety of mammalian and insect cells and on Sodalis glossindius, a bacterial symbiont of the tsetse vector. The fluorescent stain rhodamine 123 was used in immunofluorescence microscopy and flow cytometry experiments to show that BMAP-18 at low concentrations rapidly disrupted mitochondrial potential without obvious alteration of parasite plasma membranes, thus inducing death by apoptosis. Scanning electron microscopy revealed that higher concentrations of BMAP-18 induced membrane lesions in the parasites as early as 15 minutes after exposure, thus killing them by necrosis. In addition to direct killing of parasites, BMAP-18 was shown to inhibit LPS-induced secretion of tumour necrosis factor alpha (TNF-alpha), a cytokine that is associated with inflammation and cachexia (wasting) in sleeping sickness patients. As a prelude to in vivo applications, high affinity antibodies to BMAP-18 were produced in rabbits and used in immuno-mass spectrometry assays to detect the intact peptide in human blood and plasma. BMAP-18, a truncated form of the potent antimicrobial BMAP-27, showed low toxicity to mammalian cells, insect cells and the tsetse bacterial symbiont Sodalis glossinidius while retaining an ability to kill a variety of species and life cycle stages of pathogenic kinetoplastid parasites in vitro. BMAP-18 also inhibited secretion of TNF-alpha, an inflammatory cytokine that plays a role in the cachexia associated with African sleeping sickness. These findings support the idea that BMAP-18 should be explored as a candidate for therapy of economically important trypanosome-infected hosts, such as cattle, fish and humans, and for paratransgenic expression in Sodalis glossinidius, a bacterial symbiont in the tsetse vector, as a strategy for interference with trypanosome transmission.


Steroid-Responsive Epilepsia Partialis Continua with Anti-Thyroid Antibodies: A Spectrum of Hashimoto's Encephalopathy?
When a neuropsychiatric symptom due to encephalopathy develops in a patient with anti-thyroid antibodies, especially when the symptom is steroid-responsive, Hashimoto's encephalopathy (HE) needs to be included in the differential diagnosis of the patient. Although HE is an elusive disease, it is thought to cause various clinical presentations including seizures, myoclonus, and epilepsia partialis continua (EPC). We present the case of a 33-year-old Japanese woman who acutely developed EPC in the right hand as an isolated manifestation. A thyroid ultrasound showed an enlarged hypoechogenic gland, and a thyroid status assessment showed euthyroid with high titers of thyroid antibodies. A brain MRI revealed a nodular lesion in the left precentral gyrus. Corticosteroid treatment resulted in a cessation of the symptom. A precentral nodular lesion can be responsible for steroid-responsive EPC in a patient with anti-thyroid antibodies and may be caused by HE. The serial MRI findings of our case suggest the presence of primary demyelination, with ischemia possibly due to vasculitis around the demyelinating lesion.


Closing the loop: best practices for cross-setting communication at ED discharge.
This study aimed to develop emergency department best practice guidelines for improved communication during patient care transitions. To our knowledge, there are no specific guidelines for communication at the point of transition from the emergency department to the community. In Rhode Island, we used a multistage collaborative quality improvement process to define best practices for emergency department care transitions. We reviewed the medical literature, consensus statements, and materials from national campaigns; gathered preferences from emergency medicine and primary care clinicians; and created guidelines that we vetted with emergency medicine clinicians and other key stakeholders. Because we did not find any guidelines that globally addressed care transitions from the emergency department, we drew from studies on patient discharge instructions and extrapolated from the evidence base available for other, related settings. Our key outcome is a set of care transition best practices for emergency departments, which can be implemented to establish measurable, communitywide expectations for cross-setting clinician-to-clinician communication. They include obtaining information about patients' outpatient clinicians, sending summary clinical information to downstream clinicians, performing modified medication reconciliation, and providing patients with effective education and written discharge instructions. The best practices provide feasible standards for evaluating and improving how patients transition out of the emergency department and can provide a framework for emergency department leaders expanding their collaboration with community partners, particularly in the context of emerging payment models. They also catalyze introspection and debate about how to improve communication and accountability across the care continuum.


Mesorhizobium camelthorni sp. nov., isolated from Alhagi sparsifolia.
Nine strains isolated from symbiotic root nodules on Alhagi sparsifolia were previously designated as representing genospecies I. Phylogenetic analyses indicated that genospecies I was related closely to Mesorhizobium alhagi (genospecies II), and clearly formed a new lineage within the genus Mesorhizobium. In this study, we differentiated genospecies I from recognized species of the genus Mesorhizobium based on phylogenetic analyses of additional core genes (recA, glnA), levels of DNA-DNA relatedness (<43.3 %), fatty acid profile (58 % C₁₈:₁ω7c, 19 % 11-methyl C₁₈:₁ω7c), and biochemical and physiological characteristics. The nine strains are therefore considered to represent a novel species of the genus Mesorhizobium, for which the name Mesorhizobium camelthorni sp. nov. is proposed. The type strain is CCNWXJ 40-4(T) (=HAMBI 3020(T) =ACCC 14549(T)).


Primary pulmonary hypertension in the elderly.
Primary pulmonary hypertension is usually considered a disease of younger adults. We reviewed the natural course of primary pulmonary hypertension in patients aged 65 years or greater. During an 8-year period, 63 elderly patients were discharged from our hospital with a diagnosis of pulmonary hypertension. In eight instances, an elevated mean pulmonary arterial pressure (greater than 25 mm Hg) could not be explained by secondary causes. These elderly patients with primary pulmonary hypertension had symptoms common to younger patients with this disease, including dyspnea (eight patients), chest pain (five), pedal edema (four), and fatigue (one). In all but one patient, the initial diagnosis was incorrect, and the patients were thought to have more common diseases of the elderly that cause similar symptoms. Coexisting medical problems were common and further obscured the correct diagnosis. Survival was significantly shorter in those patients with symptoms of less than 6 months' duration. Primary pulmonary hypertension should be considered in the differential diagnosis in elderly patients with unexplained dyspnea and chest pain.


Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized, double-blind, multicentre study.
The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinson's disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations. Patients were randomized in a 3 : 2 ratio to entacapone 200 mg or placebo, administered with each dose of levodopa. Efficacy was judged on the improvement of "on" and "off" time while awake (Patient Diary and UPDRS part IV Item 39), Investigators' Global Assessment, the SF-36 Health Survey, and changes in levodopa dosages. Patients were monitored for adverse events, laboratory safety and vital signs throughout the study. Improvements in "on" time as assessed using patient diary data showed a trend in favour of entacapone, however these did not reach statistical significance. "Off" time while awake (UPDRS part IV Item 39) showed an improvement of at least one category in 36% of entacapone-treated patients, compared with 22% in the control group (p = 0.0038). The proportion of patients showing an improvement at the Investigators' Global Assessment was significantly higher (p = 0.0006) in the entacapone-treated group of patients. Also, the proportion of patients with a reduction in their daily levodopa dose was significantly higher (p = 0.02) in the entacapone group (28%) compared with placebo (13%). As expected, the most frequent adverse events were dopamine-mediated (dyskinesia: entacapone 31% versus placebo 13%), and harmless urinary discoloration. The modest increase in dyskinesias could be readily managed by levodopa down-adjustment, and, at study end there was no significant difference for the UPDRS "overall dyskinesia score" between entacapone and placebo. In conclusion, although the primary efficacy variable did not reach statistical significance, the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy.


Geriatric Depressive Symptoms in Myanmar: Incidence and Associated Factors.
Myanmar is one of many countries currently facing a growing older adult population; yet, the mental health status of the country's older adults is understudied. This is the first article to investigate the prevalence of geriatric depressive symptoms and its associated factors in Myanmar. We use data from the most recent large-scale older adult survey conducted in 2016, which employed the four-item short version of the Geriatric Depression Scale (GDS-4). Descriptive statistics reveal that, depending on the threshold applied, about 16% to 56% of the surveyed older adults have indications of depressive symptoms. We find that both economic and health status have a statistically significant association with depressive symptoms, but no basic individual characteristics are associated with it. Our findings suggest the importance of a social security system for older adults. Expanding the scope of the pension scheme and improving the provision of health care may be among the important policy options.


An analysis of the microwave dielectric properties of solvent-oil feedstock mixtures at 300-3000 MHz.
Microwaves can be a more efficient method than traditional thermal treatment to deliver the energy required for heating in solvent-oil extraction due to its volumetric, direct coupling with the material. An understanding of the behavior of dielectric properties of solvent-feedstock mixtures is important for designing and optimizing any microwave-based extraction process. In this study rice bran and soybean flour were mixed separately with four different solvents (methanol, ethanol, hexane and isopropanol) at different ratios (1:2, 1:1, 2:1 w/w). For the samples mixed with ethanol, the dielectric properties were measured at 23, 30, 40 and 50 degrees C, while for all other sample-solvent mixtures experiments were performed at room temperature. Dielectric properties were determined using a vector network analyzer and dielectric probe kit using the open-ended coaxial probe method in the frequency range of 300 MHz to 3 GHz. Results from the study indicate that dielectric constants were dependent on frequency and were strongly influenced by temperature, mix ratio and solvent type. The dielectric loss of all mixtures except those with hexane (which were virtually zero) varied with frequency and temperature, solvent type, and mix ratio. Most of the results presented are emphasized at 433, 915 and 2450 MHz, frequencies allocated by the Federal Communication Commission (F.C.C.) for microwave applications. The results of the study, presented here for the first time to our knowledge, will help in selection of appropriate solvent, mixing ratio and frequency for designing microwave-assisted oil extraction systems.


[Patient anxiety before surgery].
At present time we have to face a new quality of fear and anxiety rooted in a social change of fundamental values. Disease and death are being increasingly ruled out from the pattern of everyday life. Therefore, disease and death represent an extreme emotional stress for today's human beings, who find it difficult to assess their significance. Against this background we must view human fear and anxiety before surgery. Nowadays, people have lost the ability of dealing with themselves and their own problems. There is no place for disease in a world dominated by materialism. Accordingly, it is an extreme challenge for any human remain psychologically stable, whereas, anxiety appears increasingly irrational. Both anaesthesiologists and surgeons are responsible for removing anxiety and affording assistance to patients expecting surgery. Consequently, contemporary strategies of therapy include both surgical and psychosocial aspects. Therefore, confidence concerning the relationship between surgeon and patient, consideration of psychosocial factors, and an interdisciplinary approach are essentially necessary to cure the patients from their disease. However, to alleviate and even remove the patients' preoperative anxiety, we must approach and meet the patient on an equal level: from human being to human being.


Effect of the Protein Corona Formation on Antibody Functionalized Liquid Lipid Nanocarriers.
The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier by coupling a specific fluorescent antibody on the surface of functionalized lipid liquid nanocapsules (LLNCs). Thus, an anti-HER2-FITC antibody (αHER2) has been used, HER2 being a surface receptor that is overexpressed in several tumor cells. Subsequently, the in vitro formation of a PC has been developed using fetal bovine serum supplemented with human fibrinogen. Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Laser Doppler Electrophoresis (LDE), and Gel Chromatography techniques have been used to assure a complete physico-chemical characterization of the nano-complexes with (LLNCs-αHER2-PC) and without (LLNCs-αHER2) the surrounding PC. In addition, cellular assays were performed to study the cellular uptake and the specific cellular-nanocarrier interactions using the SKBR3 (high expression of HER2) breast cancer cell line and human dermal fibroblasts (HDFa) (healthy cell line without expression of HER2 receptors as control), showing that the SKBR3 cell line had a higher transport rate (50-fold) than HDFa at 60 min with LLNCs-αHER2. Moreover, the SKBR3 cell line incubated with LLNCs-αHER2-PC suffered a significant reduction (40%) in the uptake. These results suggest that the formation of a PC onto LLNCs does not prevent specific cell targeting, although it does have an important influence on cell uptake.


Automatic robust neurite detection and morphological analysis of neuronal cell cultures in high-content screening.
Cell-based high content screening (HCS) is becoming an important and increasingly favored approach in therapeutic drug discovery and functional genomics. In HCS, changes in cellular morphology and biomarker distributions provide an information-rich profile of cellular responses to experimental treatments such as small molecules or gene knockdown probes. One obstacle that currently exists with such cell-based assays is the availability of image processing algorithms that are capable of reliably and automatically analyzing large HCS image sets. HCS images of primary neuronal cell cultures are particularly challenging to analyze due to complex cellular morphology. Here we present a robust method for quantifying and statistically analyzing the morphology of neuronal cells in HCS images. The major advantages of our method over existing software lie in its capability to correct non-uniform illumination using the contrast-limited adaptive histogram equalization method; segment neuromeres using Gabor-wavelet texture analysis; and detect faint neurites by a novel phase-based neurite extraction algorithm that is invariant to changes in illumination and contrast and can accurately localize neurites. Our method was successfully applied to analyze a large HCS image set generated in a morphology screen for polyglutamine-mediated neuronal toxicity using primary neuronal cell cultures derived from embryos of a Drosophila Huntington's Disease (HD) model.


Susceptibility of Microsporum canis arthrospores to a mixture of chemically defined essential oils: a perspective for environmental decontamination.
The zoophilic dermatophyte Microsporum canis has cats as natural reservoir, but it is able to infect a wide range of hosts, including humans, where different clinical features of the so-called ringworm dermatophytosis have been described. Human infections are increasingly been reported in Mediterranean countries. A reliable control program against M. canis infection in cats should include an antifungal treatment of both the infected animals and their living environment. In this article, a herbal mixture composed of chemically defined essential oils (EOs) of Litsea cubeba (1%), Illicium verum, Foeniculum vulgare, and Pelargonium graveolens (0.5% each) was formulated and its antifungal activity assessed against M. canis arthrospores which represent the infective environmental stage of M. canis. Single compounds present in higher amounts in the mixture were also separately tested in vitro. Litsea cubeba and P. graveolens EOs were most effective (minimum inhibitory concentration (MIC) 0.5%), followed by EOs of I. verum (MIC 2%) and F. vulgare (MIC 2.5%). Minimum fungicidal concentrations (MFC) values were 0.75% (L. cubeba), 1.5% (P. graveolens), 2.5% (I. verum) and 3% (F. vulgare). MIC and MFC values of the mixture were 0.25% and 0.5%, respectively. The daily spray of the mixture (200 μL) directly onto infected hairs inhibited fungal growth from the fourth day onwards. The compounds present in higher amounts exhibited variable antimycotic activity, with MIC values ranging from >10% (limonene) to 0.1% (geranial and neral). Thus, the mixture showed a good antifungal activity against arthrospores present in infected hairs. These results are promising for a further application of the mixture as an alternative tool or as an adjuvant in the environmental control of feline microsporosis.


Atomic structural analysis of nanowire defects and polytypes enabled through cross-sectional lattice imaging.
Correlated transmission electron microscopy imaging, electron diffraction, and Raman spectroscopy are used to investigate the structure of Si nanowires with planar defects. In addition to plan-view imaging, individual defective nanowires are imaged in axial cross-section at specific locations selected in plan-view imaging. This correlated characterization approach enables definitive identification of complex defect structures that give rise to diffraction patterns that have been misinterpreted in the literature. Conclusive evidence for the 9R Si polytype is presented, and the atomic structure of this phase is correlated with kinematically-forbidden reflections in Si diffraction patterns. Despite striking similarities between imaging and diffraction data from twinned nanowires and the 9R polytype, clear distinctions between the structures can be made. Finally, the structural origins of ⅓{422} reflections in Si [111] diffraction patterns are identified.


Robotic partial nephrectomy versus radical nephrectomy in elderly patients with large renal masses.
Recent evidence suggests that the "oldest old" patients might benefit of partial nephrectomy (PN), but decision-making for this subset of patients is still controversial. Aim of this study is to compare outcomes of robotic partial (RPN) or radical nephrectomy (RRN) for large renal masses in patients older than 65 years. We identified 417≥65 years old patients who underwent RRN or RPN for cT1b or ≥cT2 renal mass at 17 high volume centers. Propensity score match analysis was performed adjusting for age, ASA≥3, pre-operative eGFR, and clinical tumor size. Predictors of complications, functional and oncological outcomes were evaluated in multivariable logistic and Cox regression models. After propensity score analysis, 73 patients in the RPN group were matched with 74 in the RRN group. R.E.N.A.L. Score (9.6±1.7 vs. 8.6±1.7; P<0.001), and high complexity (56 vs. 15%; P=0.001) were higher in the RRN. Estimated blood loss was higher in the RPN group (200 vs. 100 mL; P<0.001). RPN showed higher rate of overall complications (38 vs. 23%; P=0.05), but not major complications (P=0.678). At last follow-up, RPN group showed better functional outcomes both in eGFR (55.4±22.6 vs. 45.7±15.7 mL/min; P=0.016) and lower eGFR variation (9.7 vs. 23.0 mL/min; P<0.001). The procedure type was not associated with recurrence free survival (RFS) (HR: 0.47; P=0.152) and overall mortality (OM) (0.22; P=0.084). RPN in elderly patients with large renal masses provides acceptable surgical, and oncological outcomes allowing better functional preservation relative to RRN. The decision to undergo RPN in this subset of patients should be tailored on a case by case basis.


Larger therapeutic window for steroid versus VEGF-A inhibitor in inflammatory angiogenesis: surprisingly similar impact on leukocyte infiltration.
The current treatments against inflammatory angiogenesis are steroids and anti-VEGF-A, such as dexamethasone and bevacizumab, respectively. However, the therapeutic windows for dexamethasone and bevacizumab against inflammatory angiogenesis are unknown. To investigate the therapeutic windows for dexamethasone and bevacizumab, we used the corneal pocket assay. IL-1β pellets were implanted in corneas of BALB/c mice that were then treated with dexamethasone or bevacizumab at different time points. Angiogenesis (area, number of vessels, and sprouting) was quantitated at various time points after implantation. Nuclear Factor-κB (NF-κB) signaling and leukocyte accumulation in inflammatory angiogenesis were examined by Western blotting, by immunohistochemistry, and in the authors' novel leukocyte transmigration assay. Dexamethasone inhibited IL-1β-induced angiogenesis when treatment started 4 days after IL-1β implantation, while bevacizumab only inhibited angiogenesis by day 2 after implantation. Both bevacizumab and dexamethasone inhibited angiogenic sprouting. Interestingly, bevacizumab did not affect NF-κB activation, which is one of the main signaling targets for steroid action. The authors' new imaging approach revealed that bevacizumab and steroid treatment blocked leukocyte infiltration into implanted corneas. VEGF-A inhibition affected angiogenic sprouting, while it was not effective against matured vessels. Both dexamethasone and bevacizumab inhibited leukocyte transmigration from angiogenic vessels; however, dexamethasone had a larger therapeutic window. These insights improve the treatment strategy in angiogenic disorders.


Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells.
The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to the accumulation of centrosomal proteins and microtubule (MT) nucleation activity at the nuclear envelope (NE) [1-4]. The relocalization of centrosomal proteins, including Pericentrin, Pcm1, and γ-tubulin, depends on Nesprin-1, an outer nuclear membrane (ONM) protein that connects the nucleus to the cytoskeleton via its N-terminal region [5-7]. Nesprins are also involved in the recruitment of kinesin to the NE and play a role in nuclear positioning in skeletal muscle cells [8-12]. However, a function for MT nucleation from the NE in nuclear positioning has not been established. Using the proximity-dependent biotin identification (BioID) method [13, 14], we found several centrosomal proteins, including Akap450, Pcm1, and Pericentrin, whose association with Nesprin-1α is increased in differentiated myotubes. We show that Nesprin-1α recruits Akap450 to the NE independently of kinesin and that Akap450, but not other centrosomal proteins, is required for MT nucleation from the NE. Furthermore, we demonstrate that this mechanism is disrupted in congenital muscular dystrophy patient myotubes carrying a nonsense mutation within the SYNE1 gene (23560 G>T) encoding Nesprin-1 [15, 16]. Finally, using computer simulation and cell culture systems, we provide evidence for a role of MT nucleation from the NE on nuclear spreading in myotubes. Our data thus reveal a novel function for Nesprin-1α/Nesprin-1 in nuclear positioning through recruitment of Akap450-mediated MT nucleation activity to the NE.


Body image and extreme attitudes toward weight in Brazilian schoolchildren (PeNSE 2012).
Adolescence is a period characterized by changes such as accelerated physical growth and sexual development. Besides having to deal with these changes, adolescents are faced with beauty standards and extreme valorization of physical appearance. This article aims to describe body image and the practice of extreme attitudes regarding weight in Brazilian students. Data from the National Survey of School Health (PeNSE) 2012 were used in this study. PeNSE 2012 has a representative sample of students in the 9th grade of elementary school in public and private schools across the country. A self-administered questionnaire on body image, practice of extreme measures in relation to weight and sociodemographic data was used. Body image and the practice of extreme attitudes were described for the total sample and according to gender. Poisson regression analyzes were used to identify differences in the practices of extreme attitudes between the different types of body image. More than 38% of the adolescents did not consider their body image as normal. Over 15% of the students referred to carry out extreme weight control practices, combining practices to loose and gain weight. Adolescents who considered themselves fat presented frequency of extreme practices for weight loss 92% higher than that shown by individuals who considered themselves normal. Similarly, adolescents who considered themselves thin presented frequency of extreme attitudes to gain weight (9.7%) higher than that shown by students who considered themselves normal (5.6%). The high frequency of extreme weight control practices among Brazilian adolescents is alarming and should be subject of measures in health and education fields.


Intra-Operative Inspired Fraction of Oxygen and the Risk of Surgical Site Infections in Patients with Type 1 Surgical Incisions.
Whether the fraction of inspired oxygen (FIO2) influences the risk of surgical site infection (SSI) is controversial. The World Health Organization and the World Federation of Societies of Anesthesiologists offer conflicting recommendations. In this study, we evaluate simultaneously three different definitions of FIO2 exposure and the risk of SSI in a large surgical population. Patients with clean (type 1) surgical incisions who developed superficial and deep organ/space SSI within 30 days after surgery from January 2003 through December 2012 in five surgical specialties were matched to specialty-specific controls. Fraction of inspired oxygen exposure was defined as (1) nadir FIO2, (2) percentage of operative time with FIO2 greater than 50%, and (3) cumulative hyperoxia exposure, calculated as the area under the curve (AUC) of FIO2 by time for the duration in which FIO2 greater than 50%. Stratified univariable and multivariable logistic regression models tested associations between FIO2 and SSI. One thousand two hundred fifty cases of SSI were matched to 3,248 controls. Increased oxygen exposure, by any of the three measures, was not associated with the outcome of any SSI in a multivariable logistic regression model. Elevated body mass index (BMI; 35+ vs. <25, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.43-2.24), surgical duration (250+ min vs. <100 min, OR 1.93, 95% CI 1.48-2.52), diabetes mellitus (OR 1.37, 95% CI 1.13-1.65), peripheral vascular disease (OR 1.52, 95% CI 1.10-2.10), and liver cirrhosis (OR 2.48, 95% CI 1.53-4.02) were statistically significantly associated with greater odds of any SSI. Surgical sub-group analyses found higher intra-operative oxygen exposure was associated with higher odds of SSI in the neurosurgical and spine populations. Increased intra-operative inspired fraction of oxygen was not associated with a reduction in SSI. These findings do not support the practice of increasing FIO2 for the purpose of SSI reduction in patients with clean surgical incisions.


What happens when the price of a tobacco retailer licence increases?
To measure the impact of a 15-fold licence fee increase on tobacco retailer licence renewals. The regulatory change increasing tobacco licence fees (from $A12.90 to $A200 per annum) took effect on 1 January 2007. Government Tobacco Licence records (n=7093) were audited for 1 year prior to, and 2 years after the change. An interrupted time series analysis using ARIMA modelling was conducted to examine the impact of fee increases on the number of active licences. The total number of tobacco licences decreased by 23.7% from December 2007 to December 2009. The increased tobacco licence fee implemented on 1 January 2007, was associated with a significant reduction in the number of tobacco licences purchased or renewed in subsequent years. Of the 1144 entertainment licensees holding valid licences in December 2007, 30.9% no longer held a licence by December 2009, and 19.9% had reduced the number of points of sale within the same venue. Licensing of tobacco retailers has received little attention in tobacco control in Australia and internationally. Our data add to the growing body of evidence supporting further regulation of retail sale of tobacco. The results demonstrate that a tobacco licence price increase off a low base is a potentially effective method of reducing tobacco points of sale when consumer demand for cigarette products is low. However, further research is needed to identify additional measures that may be necessary to reduce the availability of tobacco products in areas where consumer demand for cigarettes is high.


Multiphysics modelling, quantum chemistry and risk analysis for corrosion inhibitor design and lifetime prediction.
Organic corrosion inhibitors can provide an effective means to extend the life of equipment in aggressive environments, decrease the environmental, economic, health and safety risks associated with corrosion failures and enable the use of low cost steels in place of corrosion resistant alloys. To guide the construction of advanced models for the design and optimization of the chemical composition of organic inhibitors, and to develop predictive tools for inhibitor performance as a function of alloy and environment, a multiphysics model has been constructed following Staehle's principles of "domains and microprocesses". The multiphysics framework provides a way for science-based modelling of the various phenomena that impact inhibitor efficiency, including chemical thermodynamics and speciation, oil/water partitioning, effect of the inhibitor on multiphase flow, surface adsorption and self-assembled monolayer formation, and the effect of the inhibitor on cathodic and anodic reaction pathways. The fundamental tools required to solve the resulting modelling from a first-principles perspective are also described. Quantification of uncertainty is significant to the development of lifetime prediction models, due to their application for risk management. We therefore also discuss how uncertainty analysis can be coupled with the first-principles approach laid out in this paper.


Carotid endarterectomy trends in the patterns and outcomes of care at academic medical centers, 1990 through 1995.
To evaluate whether the patterns of inpatient care and patient characteristics have changed for patients undergoing a carotid endarterectomy across a group of academic medical centers from 1990 through 1995. If changes occurred, we investigated whether they had an impact on patient outcomes. Retrospective evaluation of patients undergoing a carotid endarterectomy using a hospital discharge data set compiled by the Academic Medical Center Consortium. Ten academic medical centers. A total of 7019 hospital admissions for patients who had 1 carotid endarterectomy performed as a principal procedure from January 1990 to December 1995. Trends in patient demographics, comorbidities, length of stay, days in the intensive care unit, and inpatient cerebral arteriogram use were determined. Patient outcomes included inpatient mortality, discharge to an institution, 30-day readmission rate, and selected diagnoses (postoperative hemorrhage, infection, or seizure; acute myocardial infarction; or cranial nerve palsy) and postprocedure diagnostic tests (computed tomography and magnetic resonance imaging of the head and electroencephalogram) indicative of complications. Over the 6-year study period, the number of carotid endarterectomies performed more than doubled and the percentage of hospital admissions for patients 65 years or older increased from 65% to 75%. The mean and median length of stay halved and the percentage of admissions with transfers to the intensive care unit decreased from 56% to 26% of cases. In addition, the percentage of cases with a cerebral arteriogram during the same admission but prior to the day of the carotid endarterectomy decreased from 52% to 27%. There were no trends in inpatient mortality, discharge to an institution, or 30-day readmission rate. There were no significant trends indicative of poorer quality of care as measured by the frequency of secondary diagnoses or postprocedure diagnostic test use. Despite dramatic changes that have occurred in patient characteristics and in hospital management practices for patients undergoing a carotid endarterectomy from 1990 to 1995, we were unable to detect any measurable impact on patient outcomes. These data have implications for monitoring and evaluating the impact of systemwide change on the overall quality of care for patients undergoing a carotid endarterectomy.


Cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure.
Studies have shown positive clinical outcomes of specialist palliative care for end-stage heart failure patients, but cost-effectiveness evaluation is lacking. To examine the cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure patients as compared to the customary palliative care service. A cost-effectiveness analysis was conducted alongside a randomized controlled trial (Trial number: NCT02086305). The costs included pre-program training, intervention, and hospital use. Quality of life was measured using SF-6D. The study took place in three hospitals in Hong Kong. The inclusion criteria were meeting clinical indicators for end-stage heart failure patients including clinician-judged last year of life, discharged to home within the service area, and palliative care referral accepted. A total of 84 subjects (study = 43, control = 41) were recruited. When the study group was compared to the control group, the net incremental quality-adjusted life years gain was 0.0012 (28 days)/0.0077 (84 days) and the net incremental costs per case was -HK$7935 (28 days)/-HK$26,084 (84 days). The probability of being cost-effective was 85% (28 days)/100% (84 days) based on the cost-effectiveness thresholds recommended both by National Institute for Health and Clinical Excellence (£20,000/quality-adjusted life years) and World Health Organization (Hong Kong gross domestic product/capita in 2015, HK$328117). Results suggest that a transitional home-based palliative care program is more cost-effective than customary palliative care service. Limitations of the study include small sample size, study confined to one city, clinic consultation costs, and societal costs including patient costs and unpaid care-giving costs were not included.


Effects of environmental enrichment and regrouping on natural autoantibodies-binding danger and neural antigens in healthy pigs with different individual characteristics.
Pigs living in commercial husbandry systems may experience both acute stress due to standard management procedures and chronic stress through limitations in their barren housing environment. This might influence their immune status, including antibody responses to neural and danger autoantigens. Levels of natural autoantibody (NAAb)-binding phosphorylcholine-conjugated bovine serum albumin (PC-BSA) and myelin basic protein (MBP) were measured over time in pigs that were kept in environmental enriched v. barren housing, and that underwent a regrouping test. In total, 480 pigs were housed in 80 pens in either barren or straw-enriched pens from 4 through 23 weeks of age. Blood samples were taken from pigs before (week 8), and 3 days after a 24 h regrouping test (week 9), and at 22 weeks of age. Phosphorylcholine-conjugated bovine serum albumin (PC-BSA) and MBP antibody titres in serum were measured using ELISA. Enriched-housed pigs had higher levels of IgM-binding MBP, and tended to have higher levels of IgG-binding MBP and IgA-binding PC-BSA than barren-housed pigs. Each NAAb measured in this study was affected by gender and litter. These results suggest that enriched housing conditions, as well as acute regrouping stress, have an influence on levels of serum NAAb-binding danger and neural antigens in pigs.


A novel role for glycogen synthase kinase-3 in Xenopus development: maintenance of oocyte cell cycle arrest by a beta-catenin-independent mechanism.
We have examined the expression of glycogen synthase kinase-3beta in oocytes and early embryos of Xenopus and found that the protein is developmentally regulated. In resting oocytes, GSK-3beta is active and it is inactivated on maturation in response to progesterone. GSK-3beta inactivation is necessary and rate limiting for the cell cycle response to this hormone and the subsequent accumulation of beta-catenin. Overexpression of a dominant negative form of the kinase accelerates maturation, as does inactivation by expression of Xenopus Dishevelled or microinjection of an inactivating antibody. Cell cycle inhibition by GSK-3beta is not mediated by the level of beta-catenin or by a direct effect on either the MAP kinase pathway or translation of mos and cyclin B1. These data indicate a novel role for GSK-3beta in Xenopus development: in addition to controlling specification of the dorsoventral axis in embryos, it mediates cell cycle arrest in oocytes.


Evaluation of image quality of a 32-channel versus a 12-channel head coil at 1.5T for MR imaging of the brain.
Multichannel phased-array head coils are undergoing exponential escalation of coil element numbers. While previous technical studies have found gains in SNR and spatial resolution with the addition of element coils, it remains to be determined how these gains affect clinical reading. The purpose of this clinical study was to determine if the SNR and spatial resolution characteristics of a 32-channel head coil result in improvements in perceived image quality and lesion evaluation. Twenty-one patients underwent MR imaging of the brain at 1.5T sequentially with both a 12-channel and a 32-channel receive-only phased-array head coil. Axial T2WIs, T1WIs, FLAIR images, and DWIs were acquired. Anonymized images were compared side-by-side and by sequence for image quality, lesion evaluation, and artifacts by 3 neuroradiologists. Results of the comparison were analyzed for the preference for a specific head coil. FLAIR and DWI images acquired with the 32-channel coil showed significant improvement in image quality in several parameters. T2WIs also improved significantly with acquisition by the 32-channel coil, while T1WIs improved in a limited number of parameters. While lesion evaluation also improved with acquisition of images by the 32-channel coil, there was no apparent improvement in diagnostic quality. There was no difference in artifacts between the 2 coils. Improvements in SNR and spatial resolution attributed to image acquisition with a 32-channel head coil are paralleled by perceived improvements in image quality.


The expression of desmoglein isoforms in cultured human keratinocytes is regulated by calcium, serum, and protein kinase C.
Three desmoglein (Dsg) isoforms are expressed in a differentiation-specific fashion in the epidermis, with Dsg2 being basal, Dsg3 (pemphigus vulgaris antigen) basal and spinous, and Dsg1 (pemphigus foliaceus antigen) predominantly granular. To better understand the mechanism(s) regulating Dsg isoform expression, we examined the expression pattern of Dsg1, Dsg2, and Dsg3 in normal human epidermal keratinocytes (NHEKs), the immortalized, nontumorigenic HaCaT cell line, and several squamous cell carcinoma cell lines (SCC-9, SCC-12F, SCC-13, and SCC-25). In all cells, the accumulation of high Dsg protein levels required calcium and was not observed in low calcium (0.05-0.07 mM) media. NHEKs expressed Dsg1 in all media tested, consistent with their normal differentiation capacity. HaCaT and SCC-25 also expressed Dsg1; however, the presence of serum in the media dramatically decreased Dsg1 protein levels. Serum also inhibited Dsg1 mRNA levels in HaCaT cells. Dsg1 was not detected in extracts from SCC-9, SCC-12F, and SCC-13 under any conditions. Since activation of protein kinase C (PKC) is involved in keratinocyte differentiation, we evaluated the effects of PKC down-regulation on Dsg isoform expression. Long-term treatment with either the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or bryostatin 1 inhibited levels of Dsg1 and Dsg3, but not Dsg2 in NHEKs and HaCaT cells. Chronic TPA also decreased Dsg1 and Dsg3 mRNA levels in NHEKs, further supporting a role for PKC activation in the expression of the suprabasal Dsg1 and Dsg3. These results identify several regulatory mechanisms by which the differentiation-specific pattern of desmosomal cadherins is established in the epidermis.


Aromatic amines and cancer.
Epidemiological evidence on the relation between aromatic amines and cancer risk is reviewed. In particular, cancer risk in humans resulting from exposure to aromatic amines from occupational sources and tobacco smoking is assessed with reference to ecologic, cohort, and case-control studies. Seven arylamines have been classified by the International Agency for Research on Cancer: benzidine-based dyes and MOCA (4,4'-methylene bis 2-choloroaniline) were considered 'probably' carcinogenic, Group 2A, because of a high level of evidence in experimental animals; two occupational chemicals (2-naphthylamine and benzidine), one drug (Chlornaphazine), and two manufacturing processes (manufacture of auramine and magenta) were included in Group 1 on the basis of 'sufficient' evidence of carcinogenicity in humans. Occupational exposures to aromatic amines explain up to 25 percent of bladder cancers in some areas of Western countries; these estimates might be higher in limited areas of developing countries. Aromatic amines contaminate the ambient air as a component of environmental tobacco smoke. There is increasing evidence that the excess of bladder cancer in smokers is attributable to aromatic amines rather than to other contaminants of tobacco smoke such as polycyclic aromatic hydrocarbons (PAH). A modulating role in the risk of bladder cancer associated with exposure to aromatic amines is played by metabolic polymorphisms, such as the N-acetyltransferase genotype, raising important social and ethical issues. The consistent observation of a difference between men and women in bladder cancer risk, after allowing for known risk factors, suggests consideration of gender-related biological determinants for future investigation.


Community analysis of arbuscular mycorrhizal fungi and bacteria in the maize mycorrhizosphere in a long-term fertilization trial.
In this study, we investigated the impact of organic and mineral fertilizers on the community composition of arbuscular mycorrhizal (AM) fungi and bacteria in the mycorrhizosphere of maize in a field experiment established in 1956, in south-east Sweden. Roots and root-associated soil aggregates were sampled four times during the growing season in 2005, in control plots and in plots amended with calcium nitrate, ammonium sulphate, green manure, farmyard manure or sewage sludge. Fungi in roots were identified by cloning and sequencing, and bacteria in soil aggregates were analysed by terminal-restriction fragment length polymorphism, cloning and sequencing. The community composition of AM fungi and bacteria was significantly influenced by the different fertilizers. Changes in microbial community composition were mainly correlated with changes in pH induced by the fertilization regime. However, other factors, including phosphate and soil carbon content, also contributed significantly to these changes. Changes in bacterial community composition and a reduction in bacterial taxon richness throughout the growing season were also manifest. The results of this study highlight the importance and significant effects of the long-term application of different fertilizers on edaphic factors and specific groups of fungi and bacteria playing a key role in arable soils.


Digital detection for tobacco control: online reactions to the 2009 U.S. cigarette excise tax increase.
The Internet is revolutionizing tobacco control, but few have harnessed the Web for surveillance. We demonstrate for the first time an approach for analyzing aggregate Internet search queries that captures precise changes in population considerations about tobacco. We compared tobacco-related Google queries originating in the United States during the week of the State Children's Health Insurance Program (SCHIP) 2009 cigarette excise tax increase with a historic baseline. Specific queries were then ranked according to their relative increases while also considering approximations of changes in absolute search volume. Individual queries with the largest relative increases the week of the SCHIP tax were "cigarettes Indian reservations" 640% (95% CI, 472-918), "free cigarettes online" 557% (95% CI, 432-756), and "Indian reservations cigarettes" 542% (95% CI, 414-733), amounting to about 7,500 excess searches. By themes, the largest relative increases were tribal cigarettes 246% (95% CI, 228-265), "free" cigarettes 215% (95% CI, 191-242), and cigarette stores 176% (95% CI, 160-193), accounting for 21,000, 27,000, and 90,000 excess queries. All avoidance queries, including those aforementioned themes, relatively increased 150% (95% CI, 144-155) or 550,000 from their baseline. All cessation queries increased 46% (95% CI, 44-48), or 175,000, around SCHIP; including themes for "cold turkey" 19% (95% CI, 11-27) or 2,600, cessation products 47% (95% CI, 44-50) or 78,000, and dubious cessation approaches (e.g., hypnosis) 40% (95% CI, 33-47) or 2,300. The SCHIP tax motivated specific changes in population considerations. Our strategy can support evaluations that temporally link tobacco control measures with instantaneous population reactions, as well as serve as a springboard for traditional studies, for example, including survey questionnaire design.


Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection.
In individuals with HIV-1 infection, depletion of CD4+ T cells is often accompanied by a malfunction of CD8+ T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort (P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 (P = 0.013), B*15:10 (P = 0.007), and B*58:02 (P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8+ T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.


Preventing cervical cancer: what are the risks and benefits of different treatments?
The studyKyrgiou M, Athanasiou A, Cieslak-Jones D. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet Oncol 2022;23:1097-108.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/prevention-of-cervical-cancer-what-are-the-risks-and-benefits-of-different-treatments/.


Radiologic case study. Neuropathic osteoarthropathy.
Diabetic osteoarthropathy is the most common neuropathic condition seen clinically in the foot. It can develop rapidly with a time course of weeks to months. Soft tissue swelling and erythema with deformity are noted clinically, usually with decreased pain sensation. However, it is important to realize that these patients frequently do have pain; it may only be disproportionate to the degree of injury. Radiographic diagnosis can predate clinical suspicion and is based on recognizing the resorptive and the productive patterns of the osteoarthropathy. Often, the first clue is recognizing the radiographic features of joint instability. Remembering that overt trauma may precipitate neuropathic osteoarthropathy will also help its recognition in the follow up of fractures.


A new twist in cellular resistance to the anticancer drug bleomycin-A5.
Bleomycin is a potent chemotherapeutic agent that can mediate cell killing by attacking the DNA. It is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas and squamous cell carcinomas of the cervix, head and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug for other types of cancers. Herein, we review recent findings from both yeast and human cells showing that uptake of bleomycin-A5 is a key mechanism that limits toxicity of the drug. We also discuss how the mammalian transporter hCT2 (SLC22A16) could be used to predict the outcome of tumor responses towards bleomycin therapy, and highlight the importance of further exploring this permease with respect to its regulation and pharmacological substrates for treating a wide range of cancers.


The relation of attachment security to adolescents' paternal and peer relationships, depression, and externalizing behavior.
The relation of attachment security to multiple domains of psychosocial functioning was examined in a community sample of 167 early adolescents. Security of attachment organization, assessed using the Adult Attachment Interview, was linked to success in establishing autonomy while maintaining a sense of relatedness both with fathers and with peers, even after accounting for predictions from qualities of the mother-teen relationship. Growth curve analyses revealed links of insecurity to increasing patterns of externalizing behavior and higher and stable patterns of depressive symptoms across adolescence. Implications for a developing theory of the connections of the attachment system to multiple domains of functioning in adolescence are discussed.


Effect of Co-inhabiting Coagulase Negative Staphylococci on S. aureus agr Quorum Sensing, Host Factor Binding, and Biofilm Formation.
Staphylococcus aureus is a commensal colonizer of both humans and animals, but also an opportunistic pathogen responsible for a multitude of diseases. In recent years, colonization of pigs by methicillin resistant S. aureus has become a problem with increasing numbers of humans being infected by livestock strains. In S. aureus colonization and virulence factor expression is controlled by the agr quorum sensing system, which responds to and is activated by self-generated, autoinducing peptides (AIPs). AIPs are also produced by coagulase negative staphylococci (CoNS) commonly found as commensals in both humans and animals, and interestingly, some of these inhibit S. aureus agr activity. Here, we have addressed if cross-communication occurs between S. aureus and CoNS strains isolated from pig nares, and if so, how properties such as host factor binding and biofilm formation are affected. From 25 pig nasal swabs we obtained 54 staphylococcal CoNS isolates belonging to 8 different species. Of these, none were able to induce S. aureus agr as monitored by reporter gene fusions to agr regulated genes but a number of agr-inhibiting species were identified including Staphylococcus hyicus, Staphylococcus simulans, Staphylococcus arlettae, Staphylococcus lentus, and Staphylococcus chromogenes. After establishing that the inhibitory activity was mediated via AgrC, the receptor of AIPs, we synthesized selective AIPs to explore their effect on adhesion of S. aureus to fibronectin, a host factor involved in S. aureus colonization. Here, we found that the CoNS AIPs did not affect adhesion of S. aureus except for strain 8325-4. When individual CoNS strains were co-cultured together with S. aureus we observed variable degrees of biofilm formation which did not correlate with agr interactions. Our results show that multiple CoNS species can be isolated from pig nares and that the majority of these produce AIPs that inhibit S. aureus agr. Further they show that the consequences of the interactions between CoNS and S. aureus are complex and highly strain dependent.


Is canine fossa access necessary for successful maxillary fungus ball treatment?
Sinus fungus ball (FB) is a non-invasive mycosis that affects immunocompetent hosts, most frequently localized in the maxillary sinus. The current golden standard treatment is surgical removal. To evaluate the effectiveness of an endonasal endoscopically assisted approach to remove a maxillary FB combined or not with a transoral approach (sinusoscopy via canine fossa). A retrospective evaluation of paranasal FB treated by functional endoscopic sinus surgery (FESS) + transoral approach, compared to those treated by a sole FESS procedure. In total, 65 out of 90 patients presented with a maxillary localization and were treated by FESS. Thirthy-three patients received a combined FESS + transoral approach and 32 received solely a FESS procedure. Antimycotic medical therapy was not used in any case. With a mean follow-up of 93 months, the treatment was successful in 62 patients (95,4%) without significant differences between the two groups. Our data confirm the efficacy of FESS in the treatment of maxillary FB. A similarity in long-term results in both groups demonstrated that transoral sinusoscopy can be avoided. With the assistance of lateral-view and flexible endoscopes, angled surgical equipment and maxillary saline solution irrigations, complete removal of the diseased material and sinus clearance can be achieved by a sole middle meatotomy, reducing both morbidity and operating time.


Consolidation therapy for adult acute myeloid leukemia: a systematic analysis according to evidence based medicine.
Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.


The costs of dementia subtypes to California Medicare fee-for-service, 2015.
Dementia is among the costliest of medical conditions, but it is not known how these costs vary by dementia subtype. The effect of dementia diagnosis subtype on direct health care costs and utilization was estimated using 2015 California Medicare fee-for-service data. Potential drivers of increased costs in Lewy body dementia (LBD), in comparison to Alzheimer's disease, were tested. 3,001,987 Medicare beneficiaries were identified, of which 8.2% had a dementia diagnosis. Unspecified dementia was the most common diagnostic category (59.6%), followed by Alzheimer's disease (23.2%). LBD was the costliest subtype to Medicare, on average, followed by vascular dementia. The higher costs in LBD were explained in part by falls, urinary incontinence or infection, depression, anxiety, dehydration, and delirium. Dementia subtype is an important predictor of health care costs. Earlier identification and targeted treatment might mitigate the costs associated with co-occurring conditions in LBD.


[Quantitive Analysis of Contents in Yogurt and Application Research with FTIR Spectroscopy].
Yogurt is a food produced by bacterial fermentation of milk. All kinds of nutrition components are changing dramatically in the process of fermentation. Therefore, it is important to establish a fast and efficient measurement technology of yogurt nutrition, which is also an important goal for food safety supervision in terms of monitoring the yogurt production process in real time. Fourier transform infrared spectroscopy (FTIR) has been widely used in the field of food safety, for it has high efficiency, high throughput, no chemical pollution, thus it can be used in the inspection of food adulteration. Our study has established a quantitative model to predict the nutrition components in yogurt, such as energy value, protein, fat, carbohydrates and sodium content. Based on the least squares (PLS) method, the model used CaF(2) film FTIR technology. The results show that the new model can be used in quality control of yogurt production process: The R(2) values of the model were 0.938 9, 0.926 6, 0.918 6, 0.941 8 and 0.977 1, comparing energetic value, protein, fat, carbohydrate and sodium contents with the original spectrum of calibration samples by cross validation. And the predictive R(2) are 0.920 5, 0.905 3, 0.908 5, 0.939 3 and 0.936 4 respectively. Thus, the model has good prediction accuracy and reliability, which provides a feasible method for the rapid measurement of yogurt quality. As a preliminary exploration of the quality control technology of dairy products, this method has a good prospect of application.


Quality of life and changes in symptom relief in patients with acute uncomplicated cystitis treated with antibiotics: a prospective, open-label, multicenter, observational study.
The purpose of this study was to investigate the effect of ciprofloxacin treatment on quality of life and symptom improvement in patients with simple cystitis. Between January 2010 and December 2010, ciprofloxacin was administered twice daily for 5 days, and changes in the patients' symptoms, the therapeutic effects, and changes in the Korean version of the Urinary Tract Infection Symptoms Assessment (UTISA) score were evaluated. Patients were classified into two groups according to the self-reported degree of symptom improvement. Significant improvement was noted in symptoms such as frequency, urgency, dysuria, tenesmus, lower abdominal discomfort, back pain, and gross hematuria. The treatment success group comprised 249 patients and the treatment failure group comprised 45 patients. Baseline frequency and urgency, tenesmus, and lower abdominal discomfort were worse in the treatment failure group, although the difference was significant only for frequency (p = 0.029) and urgency (p = 0.028). All UTISA subcategory scores showed improvement in the treatment success group, and the median time to symptom improvement was 2.40 days. In the treatment failure group, some UTISA subcategory scores showed significant improvement, including those for dysuria (1.67 to 0.89), tenesmus (1.76 to 1.08), and gross hematuria (0.80 to 0.21), although significant improvement in frequency, urgency, lower abdominal discomfort, and back pain was not observed. The UTISA questionnaire was useful in reflecting the severity of simple cystitis symptoms. Frequency, urgency, lower abdominal discomfort, and back pain were not adequately improved in the treatment failure group, with frequency and urgency being predisposing factors for treatment failure.


EZH2 Is Overexpressed in BRCA1-like Breast Tumors and Predictive for Sensitivity to High-Dose Platinum-Based Chemotherapy.
BRCA1-deficient breast cancers carry a specific DNA copy-number signature ("BRCA1-like") and are hypersensitive to DNA double-strand break (DSB) inducing compounds. Here, we explored whether (i) EZH2 is overexpressed in human BRCA1-deficient breast tumors and might predict sensitivity to DSB-inducing drugs; (ii) EZH2 inhibition potentiates cisplatin efficacy in Brca1-deficient murine mammary tumors. EZH2 expression was analyzed in 497 breast cancers using IHC or RNA sequencing. We classified 370 tumors by copy-number profiles as BRCA1-like or non-BRCA1-like and examined its association with EZH2 expression. Additionally, we assessed BRCA1 loss through mutation or promoter methylation status and investigated the predictive value of EZH2 expression in a study population of breast cancer patients treated with adjuvant high-dose platinum-based chemotherapy compared with standard anthracycline-based chemotherapy. To explore whether EZH2 inhibition by GSK126 enhances sensitivity to platinum drugs in EZH2-overexpressing breast cancers we used a Brca1-deficient mouse model. The highest EZH2 expression was found in BRCA1-associated tumors harboring a BRCA1 mutation, BRCA1-promoter methylation or were classified as BRCA1 like. We observed a greater benefit from high-dose platinum-based chemotherapy in BRCA1-like and non-BRCA1-like patients with high EZH2 expression. Combined treatment with the EZH2 inhibitor GSK126 and cisplatin decreased cell proliferation and improved survival in Brca1-deficient mice in comparison with single agents. Our findings demonstrate that EZH2 is expressed at significantly higher levels in BRCA1-deficient breast cancers. EZH2 overexpression can identify patients with breast cancer who benefit significantly from intensified DSB-inducing platinum-based chemotherapy independent of BRCA1-like status. EZH2 inhibition improves the antitumor effect of platinum drugs in Brca1-deficient breast tumors in vivo.


An evidence-based method for examining and reporting cognitive processes in nutrition research.
Cognitive outcomes are frequently implemented as endpoints in nutrition research. To reduce the number of statistical comparisons it is commonplace for nutrition researchers to combine cognitive test results into a smaller number of broad cognitive abilities. However, there is a clear lack of understanding and consensus as to how best execute this practice. The present paper reviews contemporary models of human cognition and proposes a standardised, evidence-based method for grouping cognitive test data into broader cognitive abilities. Both Carroll's model of human cognitive ability and the Cattell-Horn-Carroll (CHC) model of intelligence provide empirically based taxonomies of human cognition. These models provide a cognitive 'map' that can be used to guide the handling and analysis of cognitive outcomes in nutrition research. Making use of a valid cognitive nomenclature can provide the field of clinical nutrition with a common cognitive language enabling efficient comparisons of cognitive outcomes across studies. This will make it easier for researchers, policymakers and readers to interpret and compare cognitive outcomes for different interventions. Using an empirically derived cognitive nomenclature to guide the creation of cognitive composite scores will ensure that cognitive endpoints are theoretically valid and meaningful. This will increase the generalisability of trial results to the general population. The present review also discusses how the CHC model of cognition can also guide the synthesis of cognitive outcomes in systematic reviews and meta-analysis.


Evidence-based disease management.
Disease management is an approach to patient care that emphasizes coordinated, comprehensive care along the continuum of disease and across health care delivery systems. Evidence-based medicine is an approach to practice and teaching that integrates pathophysiological rationale, caregiver experience, and patient preferences with valid and current clinical research evidence. Using diabetes mellitus as an example, we describe the importance of evidence-based medicine to the development of disease management programs. We present a method for developing and implementing evidence-based clinical guidelines, clinical pathways, and algorithms and describe the creation of systems to measure and report processes and outcomes that could drive quality improvement in diabetes care. Multidisciplinary teams are ideally suited to develop, lead, and implement evidence-based disease management programs, since they play an essential role in the preventive, diagnostic, and therapeutic decisions for patients with diabetes throughout the course of their disease.


Usefulness of adjunctive alpha1-adrenergic antagonists after single extracorporeal shock wave lithotripsy session in ureteral stone expulsion.
We evaluate the efficiency of α-adrenergic antagonists on stone clearance after extracorporeal shock wave lithotripsy (ESWL) in patients with lower ureteral stones. A total of 356 patients with solitary lower ureteral stones who underwent single ESWL sessions were divided into 2 groups. Group 1 received our standard medical therapy, and Group 2 was treated with 0.4 mg/day tamsulosin for a maximum of 2 weeks. All patients were re-evaluated with plain film radiography and ultrasound each week during the treatment period. A computed tomography scan was systematically performed 3 months after ESWL. In total, 82 of the 170 patients in Group 1 (48.2%) and 144 of the 186 patients in Group 2 (77.4%) (p = 0.002) were stone-free. Among the patients with stones 10 to 15 mm in diameter, the stone-free rate was 38.4% in Group 1 and 77.1% in Group 2 (p = 0.003). Average stone expulsion time was 10.6 days and 8.4 days in Groups 1 and 2, respectively. Ureteral colic occurred in 40 patients (23.5%) in Group 1, but only in 10 patients (5.3%) in Group 2 (p = 0.043). The only side effect of tamsulosin was slight dizziness in 5 of the 186 patients in Group 2 (2.6%). Adjunctive therapy with α1-adrenergic antagonists after ESWL is more efficient than, and equally as safe as, lithotripsy alone to manage patients with lower ureteral stones. The adding of α-blockers is more reliable and helpful for stones with a large dimension, and can also decrease stone elimination time and episodes of ureteral colic.


[Anesthesia for carbon dioxide laser surgery to correct Zenker's diverticulum].
Two 48- and 62-year-old men, the latter with a history of ischemic heart disease, underwent endoscopic carbon dioxide laser surgery to correct Zenker's diverticulum. We provided total intravenous anesthesia, taking into consideration the special requirements of laser surgery. The pathogenesis of Zenker's diverticulum, the most common type of esophageal diverticulum, is poorly understood and the treatment approach depends on size and overall patient status. Patients with Zenker's diverticulum need a thorough preoperative assessment with special attention to airway permeability and the degree of difficulty of intubation. Anesthesia should be maintained in a manner that provides the safest, most effective surgical conditions.


Beta-catenin signaling increases in proliferating NG2+ progenitors and astrocytes during post-traumatic gliogenesis in the adult brain.
Wnt/beta-catenin signaling can influence the proliferation and differentiation of progenitor populations in the hippocampus and subventricular zone, known germinal centers in the adult mouse brain. It is not known whether beta-catenin signaling occurs in quiescent glial progenitors in cortex or spinal cord, nor is it known whether beta-catenin is involved in the activation of glial progenitor populations after injury. Using a beta-catenin reporter mouse (BATGAL mouse), we show that beta-catenin signaling occurs in NG2 chondroitin sulfate proteoglycan+ (NG2) progenitors in the cortex, in subcallosal zone (SCZ) progenitors, and in subependymal cells surrounding the central canal. Interestingly, cells with beta-catenin signaling increased in the cortex and SCZ following traumatic brain injury (TBI) but did not following spinal cord injury. Initially after TBI, beta-catenin signaling was predominantly increased in a subset of NG2+ progenitors in the cortex. One week following injury, the majority of beta-catenin signaling appeared in reactive astrocytes but not oligodendrocytes. Bromodeoxyuridine (BrdU) paradigms and Ki-67 staining showed that the increase in beta-catenin signaling occurred in newly born cells and was sustained after cell division. Dividing cells with beta-catenin signaling were initially NG2+; however, by four days after a single injection of BrdU, they were predominantly astrocytes. Infusing animals with the mitotic inhibitor cytosine arabinoside prevented the increase of beta-catenin signaling in the cortex, confirming that the majority of beta-catenin signaling after TBI occurs in newly born cells. These data argue for manipulating the Wnt/beta-catenin pathway after TBI as a way to modify post-traumatic gliogenesis.


Medial and Lateral Posterior Tibial Slope Are Independent Risk Factors for Noncontact ACL Injury in Both Men and Women.
Higher posterior tibial slope (PTS) is a risk factor for anterior cruciate ligament (ACL) injury in men and women. The individual contribution of the lateral (LPTS) and medial (MPTS) slope has not yet been investigated. To determine whether either the LPTS or the MPTS is an independent risk factor for ACL injury, and to determine sex-specific differences between patients with ACL-deficient and ACL-intact knees. Cohort study; Level of evidence, 3. We reviewed knee magnetic resonance (MR) images performed on ACL-deficient and ACL-intact knees between January 2018 and June 2020 at a single institution. Inclusion criteria were isolated ACL injury and noncontact mechanism (ACL-deficient group) and nonspecific knee pain and no history of injury (ACL-intact group). Exclusion criteria for both groups were the following: previous knee surgery; meniscal, collateral ligament, posterior cruciate ligament, or multiligamentous injuries; radiological evidence of osteoarthritis; and chondral damage on the tibia. The MR images were used to establish the posterior bony slope at 25%, 50%, and 75% from the medial and/or lateral border of the tibial plateau with respect to the proximal tibial anatomic axis. One-way analysis of variance (ANOVA) was used to determine differences in PTS at the 25%, 50%, and 75% distances for the medial and lateral tibial plateau between the groups and between the sexes. Overall, 325 images were included (mean age, 36.1 ± 11.1 years; 142 ACL-deficient images [82 men and 60 women]; 183 ACL-intact images [112 men and 71 women]). MPTS and LPTS were significantly higher at 25%, 50%, and 75% in the ACL-deficient group (range, -2.7° to -5.7°) compared with the ACL-intact group (range, -2.1° to 1.5°; P = .00001). Similarly, MPTS and LPTS were significantly different in men versus women (P = .00001). ANOVA revealed that there were no significant differences in PTS between men and women for all measures (MPTS, LPTS, ACL-deficient, ACL-intact; P = .68). The study results demonstrated that higher MPTS and LPTS is a potential risk factor for ACL injury in both men and women. However, despite being highly statistically significant, the differences between groups and sexes were small and may not be clinically relevant.


The nodulation and nyctinastic leaf movement is orchestrated by clock gene LHY in Medicago truncatula.
As sessile organisms, plants perceive, respond, and adapt to the environmental changes for optimal growth and survival. The plant growth and fitness are enhanced by circadian clocks through coordination of numerous biological events. In legume species, nitrogen-fixing root nodules were developed as the plant organs specialized for symbiotic transfer of nitrogen between microsymbiont and host. Here, we report that the endogenous circadian rhythm in nodules is regulated by MtLHY in legume species Medicago truncatula. Loss of function of MtLHY leads to a reduction in the number of nodules formed, resulting in a diminished ability to assimilate nitrogen. The operation of the 24-h rhythm in shoot is further influenced by the availability of nitrogen produced by the nodules, leading to the irregulated nyctinastic leaf movement and reduced biomass in mtlhy mutants. These data shed new light on the roles of MtLHY in the orchestration of circadian oscillator in nodules and shoots, which provides a mechanistic link between nodulation, nitrogen assimilation, and clock function.


Transseptal interforniceal endoscopic removal of superiorly recessed colloid cysts.
Transforaminal endoscopic colloid cyst resection is well described. However, some anatomical colloid cyst variants may warrant a modified approach. Rarely, colloid cysts separate the forniceal columns and grow superiorly within the leaflets of the septum pellucidum. Thus, the authors' goal was to characterize the imaging features, clinical presentation, surgical strategy, and outcomes of patients with this superiorly recessed colloid cyst variant. A retrospective evaluation of patients who underwent endoscopic resection of colloid cysts from 1999 to 2020 was performed. The patients were dichotomized depending on whether the cyst was located predominately below the forniceal columns or was superiorly recessed (forniceal column separation with variable intraseptal extension). This comparative cohort study focused on clinical presentation, imaging features, operative technique, and patient outcome. In total, 182 patients were identified. Seventeen patients had colloid cysts that were defined as superiorly recessed and underwent transseptal interforniceal removal, and 165 patients underwent a standard transforaminal approach. Patients had similar demographic characteristics. However, transseptal cysts were on average larger (17.8 mm vs 11.4 mm, p < 0.0001), and these patients had a greater frontal-occipital horn ratio (0.45 vs 0.41, p = 0.012). They were also more likely to have undergone a previous resection (p = 0.02). The two cohorts had similar surgical outcomes, with no differences in extent of resection, recurrence, or complications. Superiorly recessed intraseptal colloid cysts are larger and tend to splay the bodies of the fornix, thus requiring a parasagittal transseptal interforniceal endoscopic approach. This achieves complete removal with comparatively negligible morbidity or rare recurrence (5.9%).


Evolution in the recommendations for oral rehydration therapy according to World Health Organisation guidelines: where to go from here?
Guidelines on the use of oral rehydration salts (ORS) have been revised over the years based on evidence from research studies and clinical experience. This paper charts the evolution in oral rehydration therapy (ORT) in the context of World Health Organisation (WHO) recommendations. Diarrhoeal disease case management, with ORT as its cornerstone, has had tremendous success in terms of implementation and outcome. To further decrease global diarrhoeal morbidity and mortality, there should be increased efforts to accelerate the introduction of safe, effective, and affordable against diarrhoeal pathogens such as cholera and rotavirus.


Mechanical stimulation and solid seeding trigger single-crystal-to-single-crystal molecular domino transformations.
Numerous studies have focused on the mechanical control of solid structures and phase changes in molecular crystals. However, the molecular-level understanding of how macroscopic forces affect the molecules in a solid remains incomplete. Here we report that a small mechanical stimulus or solid seeding can trigger a single-crystal-to-single-crystal transformation from a kinetically isolated polymorph of phenyl(phenyl isocyanide)gold(I) exhibiting blue photoluminescence to a thermodynamically stable polymorph exhibiting yellow emission without the need for heating or solvent. The phase transformation initiates at the location of the mechanical stimulation or seed crystal, extends to adjacent crystals, and can be readily monitored visually by the accompanying photoluminescent colour change from blue to yellow. The transformation was characterized using single crystal X-ray analysis. Our results suggest that the transformation proceeds through self-replication, causing the complex to behave as 'molecular dominoes'.


A case of primary aldosteronism with end stage renal disease.
A 52-year-old woman was referred to our hospital due to chronic renal failure with a 10-year history of hypertension. We found polycystic kidney disease, pulmonary tuberculosis and an aldosterone-producing adrenocortical mass. At this time, her serum potassium level and blood pressure were within the normal range. She refused hemodialysis and then was hospitalized because of uremic encephalopathy. On admission, her serum potassium level was normal without treatment and plasma aldosterone concentration highly elevated. She received hemodialysis, and thereafter hypokalemia developed. We then administered spironolactone, whereupon serum potassium level returned to the normal range. In this case, we thought that normokalemia was balanced hypokalemia of primary aldosteronism with hyperkalemia of chronic renal failure, and that hypokalemia developed after hemodialysis was due to an imbalanced primary aldosteronism with end stage renal disease.


Coronavirus disease 2019: a comprehensive review and meta-analysis on cardiovascular biomarkers.
Preventive cardiology has an important role to play in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The SARS-CoV-2 pandemic has been observed to have a greater mortality impact on subgroups of people in the population who are deemed to be at higher medical disease risk. Individuals with cardiovascular disorders are one such COVID-19-associated high-mortality risk group. Evidence is accumulating that COVID-19 infection may worsen an individual's future cardiovascular health, and, preinfection/postinfection cardiovascular evaluation may be warranted to determine if progressive cardiovascular damage has occurred because of COVID-19 infection. In this study, we conducted a systematic review and meta-analysis, focusing on the association between COVID-19 severity and cardiac-specific biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T (TnT)/troponin I (TnI), lactate dehydrogenase (LDH), creatine kinase, and creatine kinase isoenzyme (CK-MB). TnT had the highest odds ratio or OR (11.83) indicating the greatest association with COVID-19 severity, followed by NT-proBNP (7.57), TnI (6.32), LDH (4.79), D-dimer (4.10), creatine kinase (3.43), and CK-MB (3.35). All of the biomarkers studied were significantly correlated with COVID-19 severity including severe symptoms, ICU care, and mortality (P < 0.0001, except P < 0.01 for CK-MB). COVID-19 infection results in short-term and long-term disease risk that may involve adverse cardiovascular health issues including heart failure. Cardiac-specific biomarkers appear to identify a subset of COVID-19 patients who have the highest risk of an adverse medical outcome. Preventive cardiology has an important role to play in the COVID-19 pandemic.The risk/benefit analysis of maintaining or eliminating the use of the angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitor (ACE-I) medications deserves further investigation.


In vivo measures of anterior scleral resistance in humans with rebound tonometry.
To measure regional variations in anterior scleral resistance (ASR) using a ballistic rebound tonometer (RBT) and examine whether the variations are significantly affected by ethnicity and refractive error (RE). ASR was measured using a RBT (iCare TA01) following calibration against the biomechanical properties of agarose biogels. Eight scleral regions (nasal, temporal, superior, inferior, inferior-nasal, inferior-temporal, superior-nasal and superior-temporal) were measured at locations 4mm from the limbus. Subjects were 130 young adults comprising three ethnic groups whose RE distributions [MSE (D) ± S.D.] incorporated individuals categorised as without-myopia (NM; MSE ≥ -0.50) and with-myopia (WM; MSE < -0.50); British-White (BW): 26 NM + 0.52 ± 1.15D; 22 WM -3.83 ± 2.89D]; British-South-Asian (BSA): [9 NM + 0.49 ± 1.06D; 11 WM -5.07 ± 3.76D; Hong-Kong-Chinese (HKC): [11 NM + 0.39 ± 0.66D; 49 WM -4.46 ± 2.70D]. Biometric data were compiled using cycloplegic open-field autorefraction and the Zeiss IOLMaster. Two- and three-way repeated measures analysis of variances (anovas) tested regional differences for RBT values across both refractive status and ethnicity whilst stepwise forward multiple linear regression was used as an exploratory test. Significant regional variations in ASR were identified for the BW, BSA and HKC (p < 0.001) individuals; superior-temporal region showed the lowest levels of resistance whilst the inferior-nasal region the highest. Compared to the BW and BSA groups, the HKC subjects displayed a significant increase in mean resistance for each respective region (p < 0.001). With the exception of the inferior region, ethnicity was found to be the chief predictor for variation in the scleral RBT values for all other regions. Mean RE group differences were insignificant. The novel application of RBT to the anterior sclera confirm regional variation in ASR. Greater ASR amongst the HKC group than the BW and BSA individuals suggests that ethnic differences in anterior scleral biomechanics may exist.


Phase II trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer.
To evaluate the combination of intravenous (IV) paclitaxel, oral estramustine, and oral etoposide in patients with advanced hormone-refractory prostate cancer. Forty patients with carcinoma of the prostate that was progressing despite hormonal therapy and who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled onto this phase II trial. Patients were treated with oral estramustine 280 mg tid and oral etoposide 100 mg/d for 7 days, with paclitaxel 135 mg/m(2) IV over 1 hour on day 2 of each 21-day treatment cycle. Patients received a maximum of six cycles of therapy. Thirty-seven patients were assessable for response. Twenty-two had measurable disease at baseline; response was not assessable in six of these patients. Overall response was 45% (10 of 22 patients; 95% confidence interval [CI], 24% to 68%), and response was 63% (10 of 16) in assessable patients. Twenty-six patients had a > or = 50% decrease from their baseline prostate-specific antigen levels during therapy, for a response rate of 65% (95% CI, 48% to 79%) by this criterion. Median duration of response was 3.2 months, with an estimated median survival of 12.8 months. Major toxicities of therapy were leukopenia (eight patients had > or = grade 4 leukopenia) and anemia. Hematologic toxicity seemed to be associated with liver metastases. Serial measurements in 24 patients using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) showed no significant change in quality of life (QOL) as a result of therapy. The combination of IV paclitaxel, oral estramustine, and oral etoposide is active in patients with advanced prostate cancer. The regimen is tolerable and does not have a significant impact on QOL as measured by the FACT-P in a limited sample of patients.


Multiphoton flow cytometry to assess intrinsic and extrinsic fluorescence in cellular aggregates: applications to stem cells.
Detection and tracking of stem cell state are difficult due to insufficient means for rapidly screening cell state in a noninvasive manner. This challenge is compounded when stem cells are cultured in aggregates or three-dimensional (3D) constructs because living cells in this form are difficult to analyze without disrupting cellular contacts. Multiphoton laser scanning microscopy is uniquely suited to analyze 3D structures due to the broad tunability of excitation sources, deep sectioning capacity, and minimal phototoxicity but is throughput limited. A novel multiphoton fluorescence excitation flow cytometry (MPFC) instrument could be used to accurately probe cells in the interior of multicell aggregates or tissue constructs in an enhanced-throughput manner and measure corresponding fluorescent properties. By exciting endogenous fluorophores as intrinsic biomarkers or exciting extrinsic reporter molecules, the properties of cells in aggregates can be understood while the viable cellular aggregates are maintained. Here we introduce a first generation MPFC system and show appropriate speed and accuracy of image capture and measured fluorescence intensity, including intrinsic fluorescence intensity. Thus, this novel instrument enables rapid characterization of stem cells and corresponding aggregates in a noninvasive manner and could dramatically transform how stem cells are studied in the laboratory and utilized in the clinic.


[Dystrophic myotonia (a clinico-morphologic study)].
The paper contains data of a clinico-morphological study of 14 patients with dystrophic myotonia. The muscular bioptate was studied by means of electron microscopy. In the muscular filaments there were 2 types of changes. In the initial phase of the disease there were focal changes in the myofibrillar apparatus, a mild hypertrophy of the sarcotubular system and an increase of the mitochondria. These changes are similar to disturbances in Thomson's myotonia. The existence of common traits in these disorders, motor disturbances and similar morphologocal changes permit to consider that they are an expression of a myotonical phenomenon. The second type of disorders was characterized by dystrophical and atrophical changes, with distinct correlations between the severity of the disease and expressiveness of morphological changes.


Direct synthesis and fluorescent imaging of bifunctionalized mesoporous iodopropyl-silica.
The cocondensation of 3-iodopropyltrimethoxysilane and tetraethoxysilane with an additional substituted trimethoxysilane (RTMS) in the presence of Pluronic P123 and hydrogen iodide yields bifunctionalized mesoporous silica. The pore-size distribution of these materials depends on the nature of the RTMS additive. Excellent results in terms of a narrow pore-size distribution were obtained with methyltrimethoxysilane. A particularly interesting bifunctionalized mesoporous material is formed by the coinclusion of iodopropyl and aminopropyl moieties. The complementary reactivity of these two functional groups is demonstrated by the selective labeling of the amino-iodo-functionalized mesoporous silica with 2-hydroxy-substituted Nile red and fluorescein isothiocyanate, allowing further characterization of the functional group distribution by confocal laser scanning microscopy.