The effectiveness of integrated care interventions in improving patient quality of life (QoL) for patients with chronic conditions. An overview of the systematic review evidence.
To determine the effectiveness of integrated care interventions in improving the Quality of Life (QoL) for patients with chronic conditions. A review of the systematic reviews evidence (umbrella review). Medline, Embase, ASSIA, PsychINFO, HMIC, CINAHL, Cochrane Library (including HTA database), DARE, and Cochrane Database of Systematic Reviews), EPPI-Centre, TRIP and Health Economics Evaluations databases. Reference lists of included reviews were searched for additional references not returned by electronic searches. English language systematic reviews or meta-analyses published since 2000 that assessed the effectiveness of interventions in improving the QoL of patients with chronic conditions. Two reviewers independently assessed reviews for eligibility, extracted data, and assessed the quality of included studies. A total of 41 reviews assessed QoL. Twenty one reviews presented quantitative data, 17 reviews were narrative and three were reviews of reviews. The intervention categories included case management, Chronic care model (CCM), discharge management, multidisciplinary teams (MDT), complex interventions, primary vs. secondary care follow-up, and self-management. Taken together, the 41 reviews that assessed QoL provided a mixed picture of the effectiveness of integrated care interventions. Case management interventions showed some positive findings as did CCM interventions, although these interventions were more likely to be effective when they included a greater number of components. Discharge management interventions appeared to be particularly successful for patients with heart failure. MDT and self-management interventions showed a mixed picture. In general terms, interventions were typically more effective in improving condition-specific QoL rather than global QoL. This review provided the first overview of international evidence for the effectiveness of integrated care interventions for improving the QoL for patients with chronic conditions.


Effects of nitrogen concentrations of Eucalyptus blakelyi foliage on the fecundity of Paropsis atomaria (Coleoptera: Chrysomelidae).
The concentration of nitrogen in the foliage of Eucalyptus blakelyi strongly influenced both the total number of eggs laid and the rate of production of eggs by female Paropsis atomaria, a chrysomelid defoliator of Eucalyptus spp. Females feeding on foliage with low levels of nitrogen laid fewer eggs at a slower rate than those feeding on foliage with high levels of nitrogen. an increase from 1.5% to 4.0% of nitrogen in the foliage increased the total number of eggs laid by 500% and the rate of production of eggs by 400%. The rate at which females fed was not influenced by the concentration of nitrogen in their food. The viability of their eggs was negatively related with the concentration of nitrogen in the diet. Females feeding on foliage with low levels of nitrogen laid eggs which were significantly heavier than those of females on high nitrogen diets. Females on high nitrogen survived significantly longer than those on low nitrogen. In the field the concentration of nitrogen in the foliage of E. blakelyi occurs over a range shown to dramatically influence both the fecundity and rate of production of eggs of P. atomaria. Nitrogen may therefore play an important role in the population dynamics of this beetle.


Metaproteomic data of maize rhizosphere for deciphering functional diversity.
Metaproteomics is a powerful tool for obtaining data on all proteins recovered directly from environmental samples at a given time. It provides a direct evidence of functional diversity and structure among microbiota present in niches and significant insights into microbial activity together with metabolomics, which is the study of the intermediate and end-products of cellular processes. Metaproteomics is a comparatively new approach which is facing a number of empirical, technical, computational and experimental design challenges that needs to be addressed. Presently only little efforts have been made to have information on microbial proteins in rhizospheric soil of maize through metagemonics approach but there is no direct evidence on functions of microbial community in this very important niche. Since rhizosphere microbiome plays important role in plant growth and development the present study is conducted to optimize the metaproteomic extraction protocol from maize rhizosphere and analyse functionality of microbial communities. We present metaproteome data from maize rhizospheric soil. Isolation of metaproteome from maize rhizosphere collected from ICAR-IISS, Mau experimental Farm was done with the standardized protocol at our laboratory and metaproteome analysis was done with the standardized pipeline. In total 696 proteins with different functions representing 244 genus and 393 species were identified. The proteome data provides direct evidence on the biological processes in soil ecosystem and is the first reported reference data from maize rhizosphere. The LC MS/MS proteomic data are available via ProteomeXchange with identifier PXD014519.


Dual pH- and Temperature-Responsive Protein Nanoparticles.
Multiply responsive protein nanoparticles are interesting for a variety of applications. Herein, we describe the synthesis of a vault nanoparticle that responds to both temperature and pH. Specifically, poly(N-isopropylacrylamide-co-acrylic acid) with a pyridyl disulfide end group was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer had a lower critical solution temperature (LCST) of 31.9 °C at pH 5, 44.0 °C at pH 6 and above 60 °C at pH 7. The polymer was conjugated to human major vault protein (hMVP), and the resulting nanoparticle was analyzed by UV-Vis, dynamic light scattering (DLS) and electron microscopy. The data demonstrated that poly(N-isopropylacrylamide-co-acrylic acid)-vault conjugate did not respond to temperatures below 60 °C at pH 7, while the nanoparticles reversibly aggregated at pH 6. Furthermore, it was shown that the vault nanoparticle structure remained intact for at least three heat and cooling cycles. Thus, these dually responsive nanoparticles may serve as a platform for drug delivery and other applications.


Encapsulation of Doxorubicin in Furcellaran/Chitosan Nanocapsules by Layer-by-Layer Technique for Selectively Controlled Drug Delivery.
Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.


Single-cell imaging mass spectrometry.
Single-cell imaging mass spectrometry (IMS) is a powerful technique used to map the distributions of endogenous biomolecules with subcellular resolution. Currently, secondary ion mass spectrometry is the predominant technique for single-cell IMS, thanks to its submicron lateral resolution and surface sensitivity. However, recent methodological and technological developments aimed at improving the spatial resolution of matrix assisted laser desorption ionization (MALDI) have made this technique a potential platform of single-cell IMS. MALDI opens the field of single-cell IMS to new possibilities, including single cell proteomic imaging and atmospheric pressure analyses; however, sensitivity is a challenge. In this report, we estimate the availability of proteins and lipids in a single cell and discuss strategies employed to improve sensitivity at the single-cell level.


Relationship between serum visfatin levels and coronary slow-flow phenomenon.
Increased levels of visfatin, a novel adipocytokine, are reported in atherosclerosis, obesity, and type 2 diabetes. The aim of the present study was to investigate the relationship between coronary slow flow (CSF) and visfatin in patients undergoing elective coronary angiography for suspected coronary artery disease. A total of 140 recruited participants (90 patients with CSF and 50 controls) were divided into two groups according to their coronary flow rates. Coronary flow was quantified by thrombolysis in myocardial infarction (TIMI) frame count (TFC). Serum visfatin levels were higher in the CSF group than in the control group (3.29 ± 1.11 vs. 2.70 ± 1.08 ng/ml, p = 0.003). A significant correlation was found between TFC and visfatin (r = 0.535, p < 0.001). The area under the receiver operating characteristic curve was 0.720 (95 % confidence interval, 0.622-0.817, p < 0.001) for visfatin in the diagnosis of CSF. If a cut-off value of 2.59 ng/ml was used, higher levels of visfatin could predict the presence of CSF with 78.9 % sensitivity and 64.0 % specificity. Visfatin levels might be a useful biomarker for predicting CSF in patients undergoing diagnostic coronary angiography.


A new FIR filter technique for solvent suppression in MRS signals.
A large water resonance is usually present in MRS signals. Time-domain quantitation methods require a good suppression of these components in order to obtain accurate parameter estimates. In this paper, we analyze one of the most successful methods for solvent suppression, the maximum-phase finite impulse response filter (MP-FIR), and identify its drawbacks. A new filtering method is proposed to overcome the limitation of MP-FIR.


Alzheimer's disease through the eye of a mouse. Acceptance lecture for the 2001 Gayle A. Olson and Richard D. Olson prize.
There is now ample evidence that beta-amyloid proteins decrease memory. The SAMP8 mouse (P8) develops an early decline in the ability to learn and to retain new information. The studies reviewed here suggest that this is due to overproduction of beta-amyloid. Both antibodies to beta-amyloid and specific antisense to the amyloid precursor protein reverse these deficits in the P8 mouse. This antisense can cross the blood brain barrier. It is hypothesized that the overproduction of beta-amyloid leads to a decline in Delta(9) desaturase activity with an alteration in membrane fatty acids. This results in altered membrane mobility leading to a decline in neurotransmitter activity and a decreased release of acetylcholine. This decreased cholinergic activity results in a decreased ability of the P8 mouse to learn and retain new information.


Influences of postharvest ATP treatment on storage quality and enzyme activity in sucrose metabolism of Malus domestica.
The respiratory metabolism of apples remains vigorous after harvest, which can accelerate the consumption of sugar, organic acid, and other substances, thus leading to a decline in quality. The influence of postharvest ATP treatment on the changes of quality parameters and sucrose metabolism-related enzyme activity in apples was investigated in this study. The results showed that applying ATP effectively repressed the respiratory rate and weight loss and maintained higher levels of soluble solids content and flesh firmness in apples. In addition, ATP treatment enhanced succinate dehydrogenase, cytochrome oxidase, sucrose phosphate synthase, and sucrose synthase synthesis activities and reduced neutral invertase, acid invertase, and sucrose synthase cleavage activities in apples. These findings suggest that applying ATP after harvest could improve the internal quality of apples by suppressing the respiratory rate and modulating sucrose metabolism.


Salvage stereotactic radiosurgery with adjuvant use of bevacizumab for heavily treated recurrent brain metastases: a preliminary report.
It is not uncommon for brain metastasis (BM) treated with stereotactic radiosurgery (SRS) to demonstrate radiographic enlargement, with the patient developing neurological deficits attributable to a lesion at the site of SRS. The management of both local recurrence and radiation-induced necrosis (RN) poses a significant therapeutic dilemma, if surgical resection is not feasible, and effective therapies have yet to be established. This preliminary study introduces our initial experience with salvage SRS using adjuvant bevacizumab for this refractory entity. We retrospectively reviewed five patients who had received salvage SRS using adjuvant bevacizumab for recurrent BM complicated by RN. The diagnosis was based on clinical features, serial imaging studies and/or histopathological findings. Patients underwent salvage SRS followed by the first cycle of bevacizumab (7.5-10 mg/kg intravenous). Bevacizumab was repeated every 3-4 weeks until tumor progression or significant toxic events. The number of bevacizumab doses ranged from 2 to 16 (median 4). Follow-up MR imaging demonstrated a clear radiographic response in all lesions. Neurological symptoms improved in three patients and stabilized in two. In two patients, bevacizumab treatment was discontinued due to anemia and gastrointestinal bleeding, respectively. At the time of data analysis, four patients had died and the other was still alive. The causes of death were neurological decline and systemic disease progression in two patients each. Salvage SRS with adjuvant bevacizumab use appeared to provide an adequate radiographic response as well as neurological palliation for selected patients with heavily treated recurrent BM complicated by RN.


TGFbeta1 and TGFbeta3 are partially redundant effectors in brain vascular morphogenesis.
Gene deletion experiments have shown that the three TGFbeta isoforms regulate distinct developmental processes. Recent work by our group and others showed that the integrins alphavbeta6 and alphavbeta8 activate latent forms of TGFbeta1 and TGFbeta3. This raises the possibility that TGFbeta1 and TGFbeta3 act redundantly in developmental processes where both isoforms are expressed and activation is by integrins. To investigate this issue, we generated mice with defective integrin-mediated TGFbeta1 activation (Tgfb1(RGE/RGE)) that were also homozygous for a null mutation in the TGFbeta3 gene. Tgfb1(RGE/RGE); Tgfb3(-/-) mice have severely perturbed development of the brain vasculature that is highly similar to that in mice lacking alphavbeta8. Some Tgfb1(RGE/RGE); Tgfb3(+/-) and Tgfb1(RGE/RGE); Tgfb3(+/+) mice have milder, background-dependent versions of the phenotype. In addition, we found that Tgfb3 gene status influences embryonic lethality due to TGFbeta1 deficiency after limited backcrossing to the BALB/c background. Conversely, Tgfb1 gene status modifies the extent of palate fusion in Tgfb3(-/-) mice after limited backcrossing to the ICR background. Our results are consistent with a functional connection between TGFbeta1 and TGFbeta3 during development based on a shared mechanism of activation.


Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia.
Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GBH. We utilized a Western diet-induced dyslipidemia mouse model and divided animals into the following four groups (n = 5 each): the normal chow diet, vehicle control (WD), simvastatin (Sim, 10 mg/kg/day simvastatin; positive control), and GBH (GBH, 300 mg/kg/day) groups. The drugs were administered for 10 weeks, and morphological changes in the liver and aorta were analyzed. The mRNA expression of genes related to cholesterol metabolism, gut microbiota, and bile acid profiles were also evaluated. The GBH group showed significantly lower levels of total cholesterol, accumulation of lipids, and inflammatory markers in the liver and aorta of Western diet-fed mice. Low-density lipoprotein cholesterol levels were significantly lower in the GBH group than in the WD group (P < 0.001). The expression of cholesterol excretion-associated genes such as liver X receptor alpha and ATP-binding cassette subfamily G member 8, as well as the bile acid synthesis gene cholesterol 7 alpha-hydroxylase, which lowers cholesterol in circulation, was increased. Furthermore, GBH inhibited the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 signaling pathway through the interactions of gut microbiota with bile acids acting as FXR ligands, which included chenodeoxycholic acid and lithocholic acid. Overall, GBH improved dyslipidemia induced by a Western diet by modulating the gut microbiota-bile acid axis.


Impact of Female Sex on Clinical Presentation and Ablation Outcomes in the CIRCA-DOSE Study.
This study sought to evaluate sex-specific differences in atrial fibrillation (AF) presentation and catheter ablation outcomes in the prospective, multicenter, randomized CIRCA-DOSE (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration) study. Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology, pathophysiology, presentation, and natural history of AF. Unfortunately, there are major gaps in our understanding of the pathophysiological basis for the observed sex-specific differences and their implications on therapy and prognosis. This study examined sex-specific differences in AF presentation, symptom severity and health-related quality of life, symptomatic and asymptomatic arrhythmia recurrence, AF burden, and health care utilization. Freedom from any atrial tachyarrhythmia and symptomatic atrial tachyarrhythmia were similar between male (hazard ratio: 1.18; 95% confidence interval: 0.85 to 1.64; p = 0.39) and female patients (hazard ratio: 1.00; 95% confidence interval: 0.62 to 1.59; p = 0.92). Post-ablation, the median AF burden (percentage time in AF) was 0.00% (interquartile range: 0.00% to 0.16%) in male patients and 0.00% (interquartile range: 0.00% to 0.17%) in female patients, with no difference observed between the sexes (p = 0.30). Periprocedural complications occurred twice as frequently in female patients (3.5% vs. 7.0%; p = 0.18). In comparison to male patients, female patients reported a significantly worse symptom score and quality of life at baseline and all follow-up intervals, but they derived similar magnitude of improvement post-ablation. There was no difference between male and female patients with respect to emergency department visits, hospitalization, cardioversion, or repeat ablation. When compared with male patients, female patients have significantly worse symptom scores and quality of life at baseline. Despite this, female patients with symptomatic paroxysmal AF derive similar benefit in freedom from recurrent arrhythmia and similar improvements in quality of life following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration [CIRCA-DOSE]; NCT01913522).


High dose rate brachytherapy in the management of lung transplant airway stenosis.
Airway complications after lung transplantation remain a major cause of postoperative morbidity and mortality. Interventional bronchoscopic management continues to be the main modality in the management of these problems. Four patients with airway stenoses after lung transplantation received high dose rate brachytherapy for management of recurrent stenosis. All 4 patients had been treated with various bronchoscopic interventions, including dilation and stenting, electrocautery ablation, and neodymium:yttrium-aluminum-garnet laser therapy. High dose rate endobronchial brachytherapy was subsequently used in all 4 patients for management of recurrent airway obstruction. The radiation dose for all 4 patients was 3 Gy at a distance of 1 cm from the center of the catheter. All four patients have had routine follow-up after endobronchial brachytherapy treatments. Of the 4 patients, 2 treated with this modality showed a significant response to therapy in that the bronchus remained free of obstruction after treatment; 1 patient had partial improvement, and 1 patient failed to show significant improvement and expired from the sequelae of persistent airway obstruction. Endobronchial brachytherapy can be an effective modality for managing recurrent stenoses caused by hyperplastic granulation tissue at the bronchial anastomosis. The optimal timing and ideal candidate for intraluminal radiation therapy for this problem remains a challenge and warrants further investigation.


Microbial Ecology of European Foul Brood Disease in the Honey Bee (Apis mellifera): Towards a Microbiome Understanding of Disease Susceptibility.
European honey bees (Apis mellifera Linnaeus) are beneficial insects that provide essential pollination services for agriculture and ecosystems worldwide. Modern commercial beekeeping is plagued by a variety of pathogenic and environmental stressors often confounding attempts to understand colony loss. European foulbrood (EFB) is considered a larval-specific disease whose causative agent, Melissococcus plutonius, has received limited attention due to methodological challenges in the field and laboratory. Here, we improve the experimental and informational context of larval disease with the end goal of developing an EFB management strategy. We sequenced the bacterial microbiota associated with larval disease transmission, isolated a variety of M.plutonius strains, determined their virulence against larvae in vitro, and explored the potential for probiotic treatment of EFB disease. The larval microbiota was a low diversity environment similar to honey, while worker mouthparts and stored pollen contained significantly greater bacterial diversity. Virulence of M. plutonius against larvae varied markedly by strain and inoculant concentration. Our chosen probiotic, Parasaccharibacter apium strain C6, did not improve larval survival when introduced alone, or in combination with a virulent EFB strain. We discuss the importance of positive and negative controls for in vitro studies of the larval microbiome and disease.


Probing the natural antibody repertoire by combinatorial cloning of IgM and IgD isotypes in phage display vectors.
It is well known that immunoglobulins with no identifiable immunogenic origin, called natural antibodies, are present in the sera of healthy individuals and their role as a defence against important pathogens has been proposed. Unfortunately, the studies are hampered by the fact that these immunoglobulins seem to have low affinity and to be polyreactive, and are commonly available in polyclonal preparations. Lately, new technologies for the production of monoclonal antibodies became available, and in particular the cloning of genes coding for antibody fragments in combinatorial phage display vectors provided a handy tool for the selection of human monoclonal antibodies. In this work, we describe the successful development of a technology for the molecular cloning of combinatorial phage display libraries containing genes coding exclusively for antibody fragment of the IgM or IgD phenotype. These libraries can be useful for molecular cloning of monoclonal antibodies of the IgM and IgD phenotype and can help elucidate the role played by natural antibodies in defence against infectious agents.


Energy metabolism in humans at a lowered ambient temperature.
Assessment of the effect of a lowered ambient temperature, ie 16 degrees C (61 degrees F), compared to 22 degrees C (72 degrees F), on energy intake (EI), energy expenditure (EE) and respiratory quotient (RQ) in men. Randomized within-subject design in which subjects stayed in a respiration chamber three times for 60 h each, once at 22 degrees C, and twice at 16 degrees C, wearing standardized clothing, executing a standardized daily activities protocol, and were fed in energy balance (EBI): no significant difference between EE and EI over 24 h). During the last 24 h at 22 degrees C, and once during the last 24 h at 16 degrees C, they were fed ad libitum. Nine dietary unrestrained male subjects (ages 24+/-5 y, body mass index (BMI) 22.7+/-2.1 kg/m(2), body weight 76.2+/-9.4 kg, height 1.83+/-0.06 m, 18+/-5% body fat). At 16 degrees C (EB), EE (total 24 h EE) was increased to 12.9+/-2.0 MJ/day as compared to 12.2+/-2.2 MJ/day at 22 degrees C (P<0.01). The increase was due to increases in sleeping metabolic rate (SMR; the lowest EE during three consecutive hours with hardly any movements as indicated by radar): 7.6+/-0.7 vs 7.2+/-0.7 MJ/day (P<0.05) and diet-induced thermogenesis (DIT; EE-SMR, when activity induced energy expenditure as indicated by radar=0): 1.7+/-0.4 vs 1.0+/-0.4 MJ/day (P<0.01). Physical activity level (PAL; EE/SMR) was 1.63-1.68. At 16 degrees C compared to at 22 degrees C, rectal, proximal and distal skin temperatures had decreased (P<0.01). RQ was not different between the two ambient temperature situations. During ad libitum feeding, subjects overate by 32+/-12% (at 22 degrees C) and by 34+/-14% (at 16 degrees C). Under these circumstances, the decrease of rectal temperature at 16 degrees C was attenuated, and inversely related to percentage overeating (r(2)=0.7; P<0.01). We conclude that at 16 degrees C, compared to 22 degrees C, energy metabolism was increased, due to increases in SMR and DIT. Overeating under ad libitum circumstances at 16 degrees C attenuated the decrease in rectal core body temperature.


Investigation on conformational order and mobility of diamondbond-C18 and C18-alkyl modified silica gels by Fourier transform infrared and solid-state NMR spectroscopy.
The effect of surface coverage and solid supports on the conformational order of alkyl chains of commercially available carbon clad zirconia based supports and synthesised C18-alkyl modified silica based supports are probed in the dry state for the first time using variable temperature Fourier transform infrared (FT-IR) and solid-state 13C NMR spectroscopy. From FT-IR spectroscopy, the conformational order of alkyl chains tethered to the substrates is examined by the analysis of CH2 symmetric and anti-symmetric stretching bands. Through solid-state 13C NMR spectroscopy, the order is inferred from the relative intensity of the main methylene carbon resonance assigned to trans and trans-gauche conformations. It is found that molecules tethered to the graphite layer experience a strongly diamagnetic component of the highly anisotropic magnetic susceptibility of the graphite lattice, which reflects upfield shift in the 13C NMR spectra of commercially available octadecyl-modified carbon clad zirconia based column materials. The present results prove that temperature, surface coverage and solid supports have an influence on the conformational order and mobility of alkyl chains tethered to the carbon clad inorganic metal oxides.


Enhancing pIFN-α production and process stability in fed-batch culture of Pichia pastoris by controlling the methanol concentration and monitoring the responses of OUR/DO levels.
Effective expression of porcine interferon-α (pIFN-α) with recombinant Pichia pastoris was conducted in a bench-scale fermentor using an in situ methanol electrode-based feeding process with the control level of methanol concentration linearly increased to 10 g l⁻¹ for the first 20 h and maintained at 10 g l⁻¹ for the rest of expression phase. With this two-stage control process, the highest pIFN-α concentration reached a level of 1.81 g l⁻¹, which was 1.5-fold of that in the previous constant 10 g l⁻¹ induction experiments. There is an improvement of the pIFN-α productivity from more distribution of carbon flux to protein expression. The pIFN-α expression stability could be further enhanced by a simple on-line fault diagnosis method for methanol overfeeding based on oxygen uptake rate changing patterns. By implementing corrective action of feeding glycerol after fault detection, the production yield increased to twice the amount it would have been without the diagnosis.


Immunologic aspects of multiple sclerosis.
Multiple sclerosis (MS) is the most common autoimmune disease involving the central nervous system. Knowledge of the basic autoimmunologic properties related to MS is critical to formulating a logical treatment approach to the patient. A review of immunologic systems and their specific applicability to MS is included in this article.


Self-care burden in women with human immunodeficiency virus.
The authors of this descriptive study used Orem's Theory of Self-Care to assess perceived demand for or change in universal and health-deviation self-care activity and the degree of difficulty ascribed to meeting that demand. Perceived demand or change in self-care and difficulty in self-care were measured using the Self-Care Burden Scale (Oberst, Hughes, Chang & McCubbin, 1991) and a structured interview. A convenience sample of 10 English or Spanish-speaking women with HIV infection utilizing a city hospital's outpatient immunodeficiency clinic were recruited. Of the health deviation self-care items, home medical/nursing treatments, special diet, and obtaining resources were the most burdensome categories. Universal self-care tasks with the highest burden scores were caring for children, physical activity, and work.


T cell up-regulation of B cells via their idiotypes contributing to the development of systemic lupus erythematosus. A hypothesis.
A mechanism for sustained production of pathogenic autoantibody subsets in patients and mice with systemic lupus erythematosus may be centered on selective up-regulation of B cells bearing certain idiotypes. Public idiotypes are characteristic of some autoantibodies, including anti-DNA. Evidence is reviewed that suggests that immunoglobulins bearing certain public idiotypes, such as IdGN2, contain autoantibody subsets that are nephritogenic in human systemic lupus erythematosus and in New Zealand black/New Zealand white F1 mice. Up-regulation of such cells could promote development of nephritis. Work from several laboratories has shown that production of immunoglobulin G antibodies to DNA depends upon T cell help. In New Zealand black/New Zealand white F1 mice, cloned T cells are dominated by autoreactive cells that produce B cell growth factors. We suggest that this sustained release of B cell growth factors combined with selection by T helper cells for B cells bearing IdGN2 are a major mechanism for sustained up-regulation of nephritogenic subsets of autoantibodies.


Exceptional arsenic (III,V) removal performance of highly porous, nanostructured ZrO2 spheres for fixed bed reactors and the full-scale system modeling.
Highly porous, nanostructured zirconium oxide spheres were fabricated from ZrO2 nanoparticles with the assistance of agar powder to form spheres with size at millimeter level followed with a heat treatment at 450 °C to remove agar network, which provided a simple, low-cost, and safe process for the synthesis of ZrO2 spheres. These ZrO2 spheres had a dual-pore structure, in which interconnected macropores were beneficial for liquid transport and the mesopores could largely increase their surface area (about 98 m(2)/g) for effective contact with arsenic species in water. These ZrO2 spheres demonstrated an even better arsenic removal performance on both As(III) and As(V) than ZrO2 nanoparticles, and could be readily applied to commonly used fixed-bed adsorption reactors in the industry. A short bed adsorbent test was conducted to validate the calculated external mass transport coefficient and the pore diffusion coefficient. The performance of full-scale fixed bed systems with these ZrO2 spheres as the adsorber was estimated by the validated pore surface diffusion modeling. With the empty bed contact time (EBCT) at 10 min and the initial arsenic concentration at 30 ppb, the number of bed volumes that could be treated by these dry ZrO2 spheres reached ~255,000 BVs and ~271,000 BVs for As(III) and As(V), respectively, until the maximum contaminant level of 10 ppb was reached. These ZrO2 spheres are non-toxic, highly stable, and resistant to acid and alkali, have a high arsenic adsorption capacity, and could be easily adapted for various arsenic removal apparatus. Thus, these ZrO2 spheres may have a promising potential for their application in water treatment practice.


LSGP-USFNet: Automated Attention Deficit Hyperactivity Disorder Detection Using Locations of Sophie Germain's Primes on Ulam's Spiral-Based Features with Electroencephalogram Signals.
Anxiety, learning disabilities, and depression are the symptoms of attention deficit hyperactivity disorder (ADHD), an isogenous pattern of hyperactivity, impulsivity, and inattention. For the early diagnosis of ADHD, electroencephalogram (EEG) signals are widely used. However, the direct analysis of an EEG is highly challenging as it is time-consuming, nonlinear, and nonstationary in nature. Thus, in this paper, a novel approach (LSGP-USFNet) is developed based on the patterns obtained from Ulam's spiral and Sophia Germain's prime numbers. The EEG signals are initially filtered to remove the noise and segmented with a non-overlapping sliding window of a length of 512 samples. Then, a time-frequency analysis approach, namely continuous wavelet transform, is applied to each channel of the segmented EEG signal to interpret it in the time and frequency domain. The obtained time-frequency representation is saved as a time-frequency image, and a non-overlapping n × n sliding window is applied to this image for patch extraction. An n × n Ulam's spiral is localized on each patch, and the gray levels are acquired from this patch as features where Sophie Germain's primes are located in Ulam's spiral. All gray tones from all patches are concatenated to construct the features for ADHD and normal classes. A gray tone selection algorithm, namely ReliefF, is employed on the representative features to acquire the final most important gray tones. The support vector machine classifier is used with a 10-fold cross-validation criteria. Our proposed approach, LSGP-USFNet, was developed using a publicly available dataset and obtained an accuracy of 97.46% in detecting ADHD automatically. Our generated model is ready to be validated using a bigger database and it can also be used to detect other children's neurological disorders.


Oral vaccination against diphtheria using polyacryl starch microparticles as adjuvant.
Oral vaccination offers the advantage of eliciting both a mucosal and a systemic immune response. This study investigated the use of polyacryl starch microparticles as adjuvant for oral vaccination against diphtheria. Diphtheria toxin or cross-reacting material (CRM197) were covalently conjugated to the microparticles and fed to mice by oral gavage. Investigation of formaldehyde treatment as a means of either detoxifying (diphtheria toxin) or stabilising (CRM197) these formulations were also made. We show that all our formulations given orally or parenterally to mice induced a strong systemic immune response. Only formulations given orally induced a mucosal IgA-response. Furthermore, our formulations given parenterally or orally induced a strong diphtheria toxin-neutralising antibody response.


Gold nanocluster with AIE: A novel photodynamic antibacterial and deodorant molecule.
Designing long-lasting yet high-efficiency antimicrobial and deodorant agents is an everlasting goal for environmental and public health. Here we present the design of AIE-featured Au nanoclusters (NCs) for visible-light-driven antibacterial and deodorant applications. Owing to the intriguing AIE traits, the good harvest of visible-light, and rich surface chemistry, the AIE-featured Au NCs unprecedentedly exhibit excellent visible-light-driven antibacterial activities against gram-positive (≥98.5%) and gram-negative bacteria (≥99.94%), which is resulted from their photodynamic producibility of abundant reactive oxygen species including O2•-, •OH and H2O2 via O2 reduction and subsequent H2O2 oxidation. In addition, the Au NCs are demonstrated to be biocompatible, and easy to be deployed for downstream antibacterial and deodorant applications. For example, the Au NCs-modified domestic materials (e.g., latex, ceramic glaze, organic fiber, and clothings) achieve long-lasting antibacterial efficiency of 99% and deodorant efficiency of >97.9% under visible-light irradiation. This work may shed light on designing novel AIE-featured metal NCs with photodynamic antibacterial and deodorant functions, enabling metal NCs and corresponding downstream materials to step into the photodynamic antibacterial and deodorant era.


Report of the Croatian Society for Neurovascular Disorders, Croatian Medical Association. Evidence based guidelines for treatment of primary headaches--2012 update.
These guidelines have been developed to assist the physician in making appropriate choices in work-up and treatment of patients with headaches. The specific aim of the Evidence Based Guidelines for Treatment of Primary Headaches--2012 Update is to provide recommendations for establishing an accurate diagnosis and choose the most appropriate therapy in the group of patients with primary headaches, based on a comprehensive review and meta-analysis of scientific evidence with regard to treatment possibilities in Croatia. These data are based on our previous Evidence Based Guidelines for Treatment of Primary Headaches published in 2005 and other recommendations and guidelines for headache treatment.


Spontaneous resolution of traumatic acute subdural haematomas: A systematic review.
Traumatic subdural haematomas often require emergency surgical evacuation. Spontaneous resolution of traumatic acute subdural haematomas (TASDH) is under-reported. Two patients are described with spontaneous resolution of TASDH correlating with previous reports. A discussion is presented on the clinical, pathological and radiological features of TASDH. A review of the literature was performed using PubMed (Medline), Embase, and Cochrane Library for similar cases. A total 21 articles were included, involving 27 cases well detailed of TASDH with spontaneous resolution or neurological and radiological improvement in less than 24 h. There are two main mechanisms for the spontaneous resolution of acute subdural haematomas: dilution in subarachnoid space and redistribution of the haematoma in the subdural space. The primary radiological characteristic of these lesions is a hypodense rim on the outer surface of the clot. Spontaneous resolution of TASDH is unusual. Clinical and radiological surveillance is essential for appropriate management of these patients.


The Use of Instrumental Variables in Peer Effects Models.
Instrumental variables are often used to identify peer effects. This paper shows that instrumenting the 'peer average outcome' with 'peer average characteristics' requires the researcher to include the instrument at the individual level as an explanatory variable. We highlight the bias that occurs when failing to do this.


Space Confinement to Regulate Ultrafine CoPt Nanoalloy for Reliable Oxygen Reduction Reaction Catalyst in PEMFC.
A Co-based zeolitic imidazolate framework (ZIF-67) derived catalyst with ultrafine CoPt nanoalloy particles is designed via a two-step space confinement method, to achieve a robust oxygen reduction reaction (ORR) performance for proton exchange membrane fuel cell (PEMFC). The core-shell structure of ZIF-67 (core) and SiO2 (shell) is carefully adjusted to inhibit the agglomeration of Co nanoparticles. In the subsequent adsorption-annealing process, the in situ formed graphene shell on the surface of Co nanoparticles further protects metal particles from coalescence, leading to the ultrafine CoPt nanoalloy (average diameter is 2.61 nm). Benefitting from the high utilization of Pt metal, the mass activity of CoPt nanoalloy catalyst reaches 681.8 mA mgPt -1 at 0.9 V versus RHE according to the rotating disk electrode test in 0.1 m HClO4 solution. The CoPt nanoalloy-based PEMFC provides a high maximum power density of 2.22 W cm-2 (H2 /O2 ) and 0.923 W cm-2 (H2 /air). Simultaneously, it shows good stability in the long-time dynamic test at low humidity, due to the robust CoPt@graphene core-shell nanostructure. This work provides a viable strategy for designing Pt-based nanoalloy catalysts with ultrafine metal particles and high stability.


Hand tapping: a simple, reproducible, objective marker of motor dysfunction in Huntington's disease.
Huntington's disease (HD) is a severe neurodegenerative condition in which the impairment in voluntary movement is related to functional disability. Clinical assessment of motor deficit currently relies largely on subjective rating scales without objective measurement. We have developed a quick and easy-to-use hand tapping device that enables measurement of (a) the number of taps in 30 seconds, (b) variability in tapping rhythm and (c) fatigue over the testing period. Initial cross-sectional testing of 178 consecutive HD clinic patients using an early model of the device showed that the total number of taps in 30 seconds correlated with the motor UHDRS (Spearmann's rho, r(s) = -0.81, p < 0.0001) and independence scores (r(s) = 0.78, p = 0.01). Longitudinal data from a small cohort followed over 10 years reveals a correlation between total number of taps in 30 seconds and motor UHDRS over time (rs = -0.49, p < 0.001), and suggests the technique may provide an objective measure of disease progression. Further tests on 15 HD patients and 9 controls were repeated three times in a single day using an updated device. The HD group made significantly fewer taps in 30 seconds (median HD = 79, control = 104, p = 0.009) and had greater variability of inter-tap interval (mean interdecile range HD = 148, control = 56, p = 0.016) compared to controls. Both the total number of taps and variability of inter-tap interval correlated with motor UHDRS. Of vital importance for any potential marker of disease progression is that these tapping parameters were reproducible with repeated measurement. Given that hand tapping parameters differ between HD and control populations, they correlate with motor UHDRS over time and are reproducible, we propose that assessment of hand tapping represents a useful objective adjunct to the clinical assessment of HD patients.


Thyroxine-evoked decrease of jejunal lactase activity in adult rats.
Daily administration of L-thyroxine (20 micrograms or 200 micrograms/100 g body weight) to adult male rats decreased jejunal lactase activity by 35% after 2-, 3-, 4- and 10 days. Four days of injections of D-thyroxine (200 micrograms/100 g body weight/day) produced a similar decrease of lactase activity. Sucrase activity was uninfluenced except for a 30% increase after daily injections of L-thyroxine (200 micrograms/100 g body weight) for 10 days. Acid beta-galactosidase activity was unaffected by either D- or L-thyroxine.


Sialosyllactotetraosylceramide, 3'-isoLM1, a ganglioside of the lactotetraose series isolated from normal human infant brain.
A ganglioside antigen was detected in infant human brains by the monoclonal antibody C-50. Structural analysis of the isolated ganglioside antigen showed it to be 3'-isoLM1, sialosyllactotetraosylceramide. The concentration of this ganglioside in human infant brain was 0.5 nmol/g.


Synchronous Sampling-Based Direct Current Estimation Method for Self-Sensing Active Magnetic Bearings.
Active magnetic bearings (AMBs) commonly use pulse-width modulation to reduce analogous hardware and manufacturing costs, but they experience sensing process, sensing accuracy and stability problems. To address these issues, a synchronous sampling-based direct current estimation (SS-DCE) method is proposed herein with a bistate switching power amplifier. First-considering the reluctance evolution mechanism of AMBs-a coupling relation mathematical model between rotor displacement and voltage/current is presented to acquire the rotor position from the working coil current alone. Then-assuming that the switching current was an approximately triangular signal-a DCE for the rotor position was established based on the estimation inductance of the charging/discharging phase. Finally-to decrease the phase shift caused by the self-sensing filters and position estimation algorithms-the SS-DCE method was introduced to conduct precise position detection for rotors with high velocities. The simulation and experimental results indicated that the proposed method could improve the sensing accuracy and stability. Compared to other AMB position estimation methods, the simple linearity of the SS-DCE method was greatly improved and could be controlled below 4%. Evaluation using frequency response analysis showed that the SS-DCE method had excellent dynamic accuracy and could perform at a higher phase margin, especially for the uprising/landing transient state. Moreover, there was a phase margin of 158° at the natural frequency of 19.26 HZ, and the peak sensitivity in the 50-250 μm range reached 10.7 dB.


Psychosocial Challenges in Solid Organ Transplantation.
Organ transplantation is often a life-saving surgery for individuals with end-stage organ disease. However, for most types of solid organ transplant, the demand for organs outweighs the supply, resulting in the need to institute a waiting list for suitable patients who cannot immediately receive an organ. Individuals who need transplants must undergo an assessment process that includes medical, surgical, and psychosocial evaluations. The transplant psychosocial evaluation considers whether surgical candidates are able and willing to care for the transplanted organ for many years. The evaluation must also consider a number of psychosocial risk factors that can lead to complications, which may cause premature loss of the graft. Some of these risk factors include a history of poor medical adherence, psychopathology (including substance use disorders), poor social support, and cognitive dysfunction. This article briefly summarizes the assessment of each of these risk factors and how they can be mitigated to ensure the best outcomes for patients and their families.


Estrogen receptor α and aryl hydrocarbon receptor cross-talk in a transfected hepatoma cell line (HepG2) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The prototype dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to exert anti-estrogenic effects via activation of the aryl hydrocarbon receptor (AhR) by interfering with the regulation of oestrogen homeostasis and the estrogen receptor α (ERα) signalling pathway. The AhR/ER cross-talk is considered to play a crucial role in TCDD- and E2-dependent mechanisms of carcinogenesis, though the concerted mechanism of action in the liver is not yet elucidated. The present study investigated TCDD's impact on the transcriptional cross-talk between AhR and ERα and its modulation by 17β-estradiol (E2) in the human hepatoma cell line HepG2, which is AhR-responsive but ERα-negative. Transient transfection assays with co-transfection of hERα and supplementation of receptor antagonists showed anti-estrogenic action of TCDD via down-regulation of E2-induced ERα signaling. In contrast, enhancement of AhR signaling dependent on ERα was observed providing evidence for increased cytochrome P450 (CYP) induction to promote E2 metabolism. However, relative mRNA levels of major E2-metabolizing CYP1A1 and 1B1 and the main E2-detoxifying catechol-O-methyltransferase were not affected by the co-treatments. This study provides new evidence of a TCDD-activated AhR-mediated molecular AhR/ERα cross-talk mechanism at transcriptional level via indirect inhibition of ERα and enhanced transcriptional activity of AhR in HepG2 cells.


[On the stress state of bone cement fixing a hip joint prosthesis (author's transl)].
Using a simplified model, tests were made to investigate the shear stress distribution at a hip joint prosthesis. A marked increase of stress at the tip of the prosthesis was found through photoelasticity. This peak stress resulted in a safety factor of 3 against exceeding the shear strength of bone cement. Since the calculation of the stress is based on unfavourable assumptions, the actual factor of safety should show a higher value still.


Progesterone and preterm birth prevention: translating clinical trials data into clinical practice.
We sought to provide evidence-based guidelines for using progestogens for the prevention of preterm birth (PTB). Relevant documents, in particular randomized trials, were identified using PubMed (US National Library of Medicine, 1983 through February 2012) publications, written in English, which evaluate the effectiveness of progestogens for prevention of PTB. Progestogens evaluated were, in particular, vaginal progesterone and 17-alpha-hydroxy-progesterone caproate. Additionally, the Cochrane Library, organizational guidelines, and studies identified through review of the above were utilized to identify relevant articles. Data were evaluated according to population studied, with separate analyses for singleton vs multiple gestations, prior PTB, or short transvaginal ultrasound cervical length (CL), and combinations of these factors. Consistent with US Preventive Task Force suggestions, references were evaluated for quality based on the highest level of evidence, and recommendations were graded. Summary of randomized studies indicates that in women with singleton gestations, no prior PTB, and short CL ≤ 20 mm at ≤ 24 weeks, vaginal progesterone, either 90-mg gel or 200-mg suppository, is associated with reduction in PTB and perinatal morbidity and mortality, and can be offered in these cases. The issue of universal CL screening of singleton gestations without prior PTB for the prevention of PTB remains an object of debate. CL screening in singleton gestations without prior PTB cannot yet be universally mandated. Nonetheless, implementation of such a screening strategy can be viewed as reasonable, and can be considered by individual practitioners, following strict guidelines. In singleton gestations with prior PTB 20-36 6/7 weeks, 17-alpha-hydroxy-progesterone caproate 250 mg intramuscularly weekly, preferably starting at 16-20 weeks until 36 weeks, is recommended. In these women with prior PTB, if the transvaginal ultrasound CL shortens to < 25 mm at < 24 weeks, cervical cerclage may be offered. Progestogens have not been associated with prevention of PTB in women who have in the current pregnancy multiple gestations, preterm labor, or preterm premature rupture of membranes. There is insufficient evidence to recommend the use of progestogens in women with any of these risk factors, with or without a short CL.


Endometriosis-induced vaginal hyperalgesia in the rat: effect of estropause, ovariectomy, and estradiol replacement.
Endometriosis (ENDO) is a painful disorder defined by extrauteral endometrial growths. It is created in rats by autotransplanting pieces of uterus (which form cysts), or, for shamENDO, fat (no cysts). ENDO induces vaginal hyperalgesia, likely via central sensitization. The severity of this hyperalgesia correlates with estradiol levels during the estrous cycle, suggesting the hyperalgesia is estradiol-modulated. If so, then hyperalgesic severity should track estradiol changes during reproductive senescence (estropause) when estradiol levels initially decrease, then increase. Using psychophysical methods to assess vaginal nociception, we found that the severity of ENDO-induced hyperalgesia paralleled estradiol changes during estropause: hyperalgesia first decreased, then returned. Furthermore, the return occurred regardless of the presence of the cysts (excised in some rats). This finding provides further support for ENDO's likely centrally-mediated effects. Additionally, the results suggest that elimination of estradiol via ovariectomy (OVX) should alleviate ENDO-induced hyperalgesia and estradiol replacement should restore it. However, in healthy and shamENDO rats, OVX produces a vaginal hyperalgesia that is alleviated by estradiol, likely via estradiol's peripheral influences on the vagina. Hence, we tested the hypothesis that OVX in ENDO rats would trigger a different type of vaginal hyperalgesia dependent on the loss of estradiol. We predicted that the opposing influences of estradiol on ENDO- and OVX-induced hyperalgesia would cancel each other. As predicted, OVX had no effect on ENDO-induced hyperalgesia and estradiol replacement alleviated it. These results suggest that, in intact rats, ENDO-induced vaginal hyperalgesia is exacerbated by estradiol, and that different mechanisms underlie ENDO-induced versus OVX-induced vaginal hyperalgesia.


Concierge, Wellness, and Block Fee Models of Primary Care: Ethical and Regulatory Concerns at the Public-Private Boundary.
In bioethics and health policy, we often discuss the appropriate boundaries of public funding; how the interface of public and private purchasers and providers should be organized and regulated receives less attention. In this paper, I discuss ethical and regulatory issues raised at this interface by three medical practice models (concierge care, executive wellness clinics, and block fee charges) in which physicians provide insured services (whether publicly insured, privately insured, or privately insured by public mandate) while requiring or requesting that patients pay for services or for the non-insured services of the physicians themselves or their associates. This choice for such practice models is different from the decision to design an insurance plan to include or exclude user fees, co-payments and deductibles. I analyze the issues raised with regards to familiar health care values of equity and efficiency, while highlighting additional concerns about fair terms of access, provider integrity, and fair competition. I then analyze the common Canadian regulatory response to block fee models, considering their extension to wellness clinics, with regards to fiduciary standards governing the physician-patient relationship and the role of informed consent. I close by highlighting briefly issues that are of common concern across different fundamental normative frameworks for health policy.


High incidence of beta-2-microglobulin containing macromolecular complexes in sarcoidosis sera.
In thirteen out of fourteen sarcoidosis patients with elevated serum levels of immune complexes beta-2-microglobulin (beta 2m) was detected in immune complex-enriched fractions prepared by precipitation with 3% polyethylene glycol. Beta-2-microglobulin was also contained in complexes isolated by means of solid-phase Clq. The levels of free beta 2m in sarcoidosis sera did not differ from the concentrations in sera from healthy donors.


Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound.
There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, Ispta: 5 W/cm(2), beam width: 5.7 mm at -6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage.


High-quality chromosome-level scaffolds of the plant bug Pachypeltis micranthus provide insights into the availability of Mikania micrantha control.
The plant bug, Pachypeltis micranthus Mu et Liu (Hemiptera: Miridae), is an effective potential biological control agent for Mikania micrantha H.B.K. (Asteraceae; one of the most notorious invasive weeds worldwide). However, limited knowledge about this species hindered its practical application and research. Accordingly, sequencing the genome of this mirid bug holds great significance in controlling M. micrantha. Here, 712.72 Mb high-quality chromosome-level scaffolds of P. micranthus were generated, of which 707.51 Mb (99.27%) of assembled sequences were anchored onto 15 chromosome-level scaffolds with contig N50 of 16.84 Mb. The P. micranthus genome had the highest GC content (42.43%) and the second highest proportion of repetitive sequences (375.82 Mb, 52.73%) than the three other mirid bugs (i.e., Apolygus lucorum, Cyrtorhinus lividipennis, and Nesidiocoris tenuis). Phylogenetic analysis showed that P. micranthus clustered with other mirid bugs and diverged from the common ancestor approximately 200 million years ago. Gene family expansion and/or contraction were analyzed, and significantly expanded gene families associated with P. micranthus feeding and adaptation to M. micrantha were manually identified. Compared with the whole body, transcriptome analysis of the salivary gland revealed that most of the upregulated genes were significantly associated with metabolism pathways and peptidase activity, particularly among cysteine peptidase, serine peptidase, and polygalacturonase; this could be one of the reasons for precisely and highly efficient feeding by the oligophagous bug P. micranthus on M. micrantha. Collectively, this work provides a crucial chromosome-level scaffolds resource to study the evolutionary adaptation between mirid bug and their host. It is also helpful in searching for novel environment-friendly biological strategies to control M. micrantha.


The survival and proliferation of fibroblasts on biocomposites containing genetically modified flax fibers: an in vitro study.
Natural fibers have long been used in several branches of industry. Nowadays, they are considered as composite materials in medicine with special focus on artificial tissue scaffolding, drug-release systems, cardiovascular patches and nerve cuffs. The purpose of this study has been to examine the in vitro biocompatibility of newly designed "green composites". Therefore, composites containing flax fibers from transgenic flax plants producing polyhydroxybutyrate (M50) and control (wt-NIKE) plants in a polylactid (PLA) or polycaprolactone (PCL) matrix were prepared and mice fibroblast viability and cytotoxicity determined after incubation for 12-48h and 3 weeks with those composites. After 24h and 48h, all green composites have a strong influence on cell viability and membrane stability without any differences among each other. The cell viability of treated cells is approximately 82.5-93% of those of untreated control cells, respectively. The increase in cytotoxicity ranged between 1.4 and 2.9 fold compared to untreated cells. After 3 weeks of incubation, no significant changes were detectable in the amount of dead and living cells between composite treated and untreated cells. In conclusion, the tested new "green composites" showed a good biocompatibility. The biocompatibility of composites from transgenic flax plant fibers producing PHB did not differ from composites of non-transgenic flax plant fibers.


Glutathione mixed disulfide inhibitors of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase.
Six glutathione-containing inhibitors of the human NADP-linked 15-hydroxyprostaglandin dehydrogenase have been isolated from placental homogenates. Glutathione disulfide is one of these inhibitors. Although the structures of the other five have not been fully elucidated, all are disulfides. Studies with these compounds and with other mixed disulfides have shown that the glutathione mixed disulfides of beta-mercaptopyruvate, mercaptoacetate, and beta-mercaptolactate are more effective inhibitors of the enzyme than are the glutathione-containing mixed disulfides isolated from placental homogenates. beta-Mercaptolactate is particularly noteworthy because of its low Ki (0.13 microM). The results reported here suggest that the activity of the prostaglandin dehydrogenase may be influenced in vivo by various glutathione mixed disulfides.


Markedly Different Effects of Monovalent Cations on the Efficiency of Gene Expression.
The effect of monovalent cations on a cell-free transcription-translation (TX-TL) system is examined using a luciferase assay. It is found that the potency for all ions analyzed here is in the order Rb+ > K+ > Cs+ > Na+ ≈ Li+ > (CH3 )4 N+ , where Rb+ is most efficient at promoting TX-TL and the ions of Li+ , Na+ , and (CH3 )4 N+ exhibit an inhibitory effect. Similar promotion/inhibition effects are observed for cell-free TL alone with an mRNA template.


Efficacy of botulinum toxin injection versus bilateral medial rectus recession for comitant esotropia: a meta-analysis.
To compare the effectiveness of botulinum toxin injection (BTX) and bilateral medial rectus recession (BMR) in the treatment of comitant esotropia. An exhaustive search of the literature from Pubmed, EMBASE, Web of Science, and Cochrane Library databases was carried out until April 2022. No language restrictions were applied. The literature was rigorously screened against eligibility criteria. Odds ratios (ORs) and 95% confidence interval (CI) were calculated. A total of 9 articles with 1100 participants were included in this meta-analysis. Three studies compared the effects of BTX to BMR on infantile esotropia, five studies compared the effects of BTX to BMR on acute acquired comitant esotropia, and one study compared the therapeutic effects between BTX and BMR for partially accommodative esotropia. Our pooled results showed that BMR achieved higher overall success rate compared with BTX (OR, 0.49; 95%CI, 0.37-0.64; P < 0.001) and patients subjected to the BTX procedure had higher overall rate of undercorrection (OR, 2.27; 95%CI,1.71-3.02; P < 0.001). No statistical difference in the overall overcorrection rate was observed between the two groups (OR = 0.42, 95% CI: 0.17 ~ 1.03, P = 0.06). Further analysis found that BMR was more effective for infantile esotropia compared to botulinum toxin injections (OR, 0.40; 95%CI, 0.27-0.57; P < 0.001). Nevertheless, the same effect was observed for BMR and BTX in the treatment of acute acquired comitant esotropia (OR, 0.97; 95%CI, 0.50-1.87; P = 0.93). The present meta-analysis indicated that the BMR procedure achieved a higher success rate and a lower undercorrection rate in patients with comitant esotropia. However, BTX demonstrated similar treatment effects to BMR surgery in the treatment of acute acquired comitant esotropia.


c-Src-mediated phosphorylation and activation of kinesin KIF1C promotes elongation of invadopodia in cancer cells.
Invadopodia on cancer cells play crucial roles in tumor invasion and metastasis by degrading and remodeling the surrounding extracellular matrices and driving cell migration in complex 3D environments. Previous studies have indicated that microtubules (MTs) play a crucial role in elongation of invadopodia, but not their formation, probably by regulating delivery of membrane and secretory proteins within invadopodia. However, the identity of the responsible MT-based molecular motors and their regulation has been elusive. Here, we show that KIF1C, a member of kinesin-3 family, is localized to the tips of invadopodia and is required for their elongation and the invasion of cancer cells. We also found that c-Src phosphorylates tyrosine residues within the stalk domain of KIF1C, thereby enhancing its association with tyrosine phosphatase PTPD1, that in turn activates MT-binding ability of KIF1C, probably by relieving the autoinhibitory interaction between its motor and stalk domains. These findings shed new insights into how c-Src signaling is coupled to the MT-dependent dynamic nature of invadopodia and also advance our understanding of the mechanism of KIF1C activation through release of its autoinhibition.


Using light to control signaling cascades in live neurons.
Understanding the complexity of neuronal biology requires the manipulation of cellular processes with high specificity and spatio-temporal precision. The recent development of synthetic photo-activatable proteins designed using the light-oxygen-voltage and phytochrome domains provides a new set of tools for genetically targeted optical control of cell signaling. Their modular design, functional diversity, precisely controlled activity and in vivo applicability offer many advantages for investigating neuronal function. Although designing these proteins is still a considerable challenge, future advances in rational protein design and a deeper understanding of their photoactivation mechanisms will allow the development of the next generation of optogenetic techniques.


Agricultural irrigation of vine crops from desalinated and brackish groundwater under an economic perspective. A case study in Siġġiewi, Malta.
Maltese agriculture faces great challenges due to the severe scarcity of water. Sufficient water resources, in quantity and quality, are necessary to cover the demand in the production of wine grape, one of the most important crops in Maltese agriculture. But also, economic efficiency is essential in the grape cultivation. A Cost-Benefit Analysis (CBA) is defined for Maltese vineyards in the Siġġiewi region, considering two irrigation scenarios, irrigation with groundwater or "do-nothing", compared with the "use non-conventional waters" from mixing water from a small desalination plant and groundwater. For the alternative 'mixing desalinated water with groundwater' it is possible to improve water availability and quality for vine crops, while increasing economic benefits for farmer. The results indicate a profitable project from a minimum area of 1 ha, but final benefit is highly dependent on the irrigated surface extension according to water price. Desalination, compared with other type of non-conventional water is considered the best option in this assessment with a small reverse osmosis (RO) desalination plant (120 m3/day) for covering the irrigation needs.


Neutrophils as potential participants in acute myocardial ischemia: relevance to reperfusion.
An interaction among leukocytes, platelets and endothelial cells is important in atherogenesis and in maintenance of blood flow and vascular tone. These complex cell-cell interactions are mediated by release of such metabolic substances as arachidonic acid metabolites, growth factors, oxygen free radicals and endothelium-derived relaxing factor. These substances participate in the regulation of blood flow in health and disease, and perturbation in the delicate equilibrium among various cellular elements may lead to evolution and propagation of myocardial ischemia. During reperfusion of ischemic myocardium, neutrophils together with platelets cause capillary plugging in the coronary microcirculation and exert detrimental effects on endothelial function resulting in the "no reflow" phenomenon, ventricular arrythmias, loss of coronary vascular reserve and, perhaps, extension of cellular injury. This review addresses the mechanisms of cell-cell interactions with special reference to myocardial ischemia and the potential for development of improved therapy to protect and preserve ischemic myocardium.


"The Reading Assistant": user-friendly technology for the visually impaired.
One important way in which optometry must respond to the needs of persons with visual disabilities is to develop innovative applications of technologies that will allow these people to function productively in the workplace, where their performance depends on the ability to read at reasonable rates: to read such documents as letters, memos, contracts, instruction manuals, newspapers, magazines, and the like. In this paper I will describe one example of such an effort, a system that is being developed jointly by the SUNY College of Optometry, the National Eye Institute, and MerlinVision Industries, Inc., a company in Yorktown Heights, NY. I have an interest in what is reported here: I hold a part-time position as Director of Clinical Research at MerlinVision.


Fluctuations in intra-ocular pressure with sleep: I. Time course of IOP increase after the onset of sleep.
Ten normal subjects slept over a series of four nights for time periods of 30 minutes, 1, 2 and 4 hours. Intra-ocular pressure (IOP) measurements were made using a non-contact tonometer before and after sleep. The subjects showed a significant increase in IOP of 3.45 mm Hg after 30 minutes of sleep and a further IOP increase thereafter to 6.41 mm Hg above baseline. Such increases in IOP after sleep in normal subjects suggest that glaucoma patients and those suspected of having glaucoma should be monitored overnight to assess their IOP control mechanisms.


Echocardiographic prediction of left ventricular dysfunction after mitral valve repair for mitral regurgitation as an indicator to decide the optimal timing of repair.
This study sought to determine whether echocardiography before mitral valve repair (MVR) for mitral regurgitation (MR) was predictive of postoperative left ventricular (LV) dysfunction and useful for deciding the optimal timing of repair. Some reports have shown that the preoperative echocardiographic data of left ventricular ejection fraction (LVEF) and left ventricular end-systolic diameter (LVDs) were good predictors of postoperative LV dysfunction. However, few reports were based on long-term follow-up data of large numbers of patients who underwent MVR in the last decade. A total of 274 patients with moderate or severe MR underwent MVR between October 1, 1991, and September 30, 2000. Among them, 171 patients who had both an operation for isolated MR due to degenerative pathology and a postoperative echocardiogram were studied. Postoperative echocardiograms were performed 3.9 +/- 2.4 years after the operation. The LVEF decreased from 66 +/- 10% before surgery to 63 +/- 11% after surgery (p < 0.0001). On univariate analysis, preoperative LVEF and LVDs correlated with postoperative LVEF (r = 0.41 and r = -0.39, respectively). Overall, postoperative LV dysfunction (defined as LVEF <50%) was not frequent (12%). However, the incidence of postoperative LV dysfunction was high in patients with preoperative LVEF <55% (38%) or LVDs > or =40 mm (23%). In patients with MR, the echocardiographic data of LVEF and LVDs were good predictors of postoperative LV dysfunction. When a decrease in LVEF or an increase in LVDs is detected, MVR should be considered to preserve postoperative LV function.


Telling the truth to young children: Ethical reasons for information disclosure in paediatrics.
When parents ask doctors not to disclose certain information to a child, doctors are challenged to articulate ethical reasons for giving information to children. This paper maps out the professional and legal landscape in which information-giving to children is taking place and identifies the key ethical arguments that have been made for disclosure of information to the child patient. We focus on pre-adolescent children, who have not reached a developmental stage that would see them regarded as 'mature minors'. While doctors can be relatively certain that professional and legal requirements will endorse their disclosure of information to the 'mature minor', guidelines are not clear on information-giving to pre-adolescents (immature minors). We identify six ethical reasons for telling the truth to younger children. It is noteworthy that there are good reasons to tell the truth to children, which are independent of any question of the child's capacity to be involved in decision-making.


New sustainable and robust catalytic supports for palladium nanoparticles generated from chitosan/cellulose film and corn stem biochar.
The production of sustainable catalytic supports for palladium nanoparticles is always desired, even more so through the recovery of biomass residues. In this sense, two different solids were investigated - chitosan/cellulose film and corn stem biochar - as catalytic supports of palladium nanoparticles. The solids were carefully characterized and tested in the Suzuki-Miyaura reaction, a typical cross-coupling reaction. The developed catalytic systems proved to be efficient and sustainable, promoted the formation of target products very well, and demanded green reactants under environmentally appropriate conditions. With the results shown in the manuscript, it is expected to contribute to the valorization of biomass and agro-industrial residues in the development of new catalysts for the chemical industry.


Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies.
Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation of T cells, preferably through the TCR complex, would result in a cascade of cytokines associated with T-cell activation and would be best able to overcome T-cell anergy. Here we use the highly attenuated MVA poxvirus to express on tumor cells, in vitro and in vivo, either of three membrane-bound monoclonal antibodies specific for murine TCR complex. Using this system, we have expressed antibodies specific for the CD3 epsilon chain (KT3), TCR alpha/beta complex (H57-597), and V beta 7 chain (TR310). Tumor cells bristling with these antibodies are capable of inducing murine T-cell proliferation and cytokine production. When injected into growing tumors (P815, RenCa, and B16F10), these constructs induce the activation of immune effector cells and result in the rejection of the tumor. Histological and FACS analysis of tumor-infiltrating leukocytes reveal that the injection of recombinant virus-expressing antibodies specific for the TCR complex attracts and activates (CD25(+), CD69(+)) CD4 and CD8 lymphocytes. This approach represents a novel strategy to overcome T-cell anergy in tumors and allow the stimulation of tumor-specific T cells.


Outpatient compared to inpatient thyroidectomy on 30-day postoperative outcomes: a national propensity matched analysis.
To address the postoperative outcomes between outpatient and inpatient neck surgery involving thyroidectomy procedures. A cohort analysis of surgical patients undergoing primary, elective, total thyroidectomy from multiple United States medical institutions who were registered with the American College of Surgeons National Surgical Quality Improvement Program from 2015 to 2018. The primary outcome was a composite score that included any 30-day postoperative adverse event. A total of 55,381 patients who underwent a total thyroidectomy were identified comprising of 14,055 inpatient and 41,326 outpatient procedures. A cohort of 13,496 patients who underwent outpatient surgery were propensity matched for covariates with corresponding number of patients who underwent inpatient thyroidectomies. In the propensity matched cohort, the occurrence of any 30-day after surgery complications were greater in the inpatient group, 424 out of 13,496 (3.1%) compared to the outpatient group, 150 out of 13,496 (1.1%), P < 0.001. Moreover, death rates were greater in the inpatient group, 22 out 13,496 (0.16%) compared to the outpatient group, 2 out of 13,496 (0.01%), P < 0.001. Similarly, hospital readmissions occurred with greater frequency in the inpatient group, 438 out of 13,496 (3.2%) compared to the outpatient group, 310 out of 13,496 (2.3%), P < 0.001. Thyroidectomy procedures performed in the outpatient setting had less rates of adverse events, including serious postoperative complications (e.g., surgical site infection, pneumonia, progressive renal insufficiency). In addition, patients who had thyroidectomy in the outpatient setting had less 30-day readmissions and mortality. Surgeons should recognize the benefits of outpatient thyroidectomy when selecting disposition of patients undergoing neck surgery.


Mental Health in Ultra-Endurance Runners: A Systematic Review.
Among ultra-endurance runners (UER), the mental, behavioral, and physical demands of training/competition can result in maladaptive outcomes. Mental health issues are common in athletes and can impact psychology, physical health, and performance. To synthesize information regarding the incidence/prevalence and factors associated with mental health issues among UER. Systematic searches were performed in PubMed, SPORTDiscus, Scopus, Cochrane databases, CINAHL, Web of Science, and Medline Ovid using key terms related to UER (e.g., trail running, road running) and psychological issues (e.g., exercise addiction, depression). Inclusion criteria included original articles published in peer-reviewed journals in English, using qualitative or quantitative approaches. We considered papers reporting incidence/prevalence and associated factors with mental health outcomes in UER of both sexes, all ages, and levels of competition (e.g., elite, nonprofessional runners). The Joanna Briggs Institute Analytical Cross-Sectional Studies critical appraisal tool was used for quality assessment. A total of 282 studies were identified, and 11 studies were included in the final selection. A total of 3670 UER were included in the studies. The prevalence of mental health issues among UER ranged between 32.0% and 62.5% for eating disorders, from 11.5% to 18.2% for exercise addiction, 18.6% for depressive symptoms, and 24.5% for sleep disturbance. Exercise addiction was not related to weekly volume, but a strong relationship with exercise in an unstructured space, age, and body mass index was shown. Mental health issues among UER are common, especially eating disorders, exercise addiction, sleep disturbances, and depressive symptoms. Further high-quality studies are needed to examine underlying factors and find preventative strategies to protect UER. The protocol of this systematic review was registered at the PROSPERO-CRD42022338743.


Critical insights into anaerobic co-digestion of wheat straw with food waste and cattle manure: Synergistic effects on biogas yield and kinetic modeling.
In this study, four batch assays were performed to ensure the synergic effects of co-digestion and find out the best inoculums to substrate ratio (ISR), carbon to nitrogen ratio (C:N), and total solid (TS) percentage in sequence. The co-digestion of three feedstocks had a 20% higher biogas yield (416 mL/gVS added) than mono-digestion with 21% volatile solids (VS) degradation. The ISR of 2 leads to the highest biogas yield (431 mL/gVS added) and VS removal (30.3%) over other ISRs (0.5, 1.0, 2.5) studied. The lower ISR (<2) tended to have lower pH due to insufficient anaerobes inside the digester. The C:N 35 (with ISR 2) yielded 17.4% higher biogas (443.5 mL/gVS added) than mono-digestion and was the highest among the C:N ratios studied with 36.6% VS removal. The VFA, alkalinity, and pH in C:N 35 assay were more stable than in other C:N assays. In the fourth batch assay, varying TS% (5, 7.5, 10, 12.5) were used with optimized ISR (2) and C:N (35). Higher TS% (10 and 12.5) had some lag phase but later achieved higher biogas production. The 12.5% TS assay achieved 80% higher biogas yield (679 mL/gVS added) over mono-digestion, i.e., highest among the TS% studied, with 48% VS removal. In conclusion, co-digestion of mixed feedstocks with ISR 2, C:N 35, and TS 12.5% could degrade almost half of the substrate available for biodegradation. Further biodegradation may require pretreatment of the recalcitrant WS. Modified Gompertz, first-order, transference, and logistic models were used for kinetic study and curve fitting of experimental data. For the optimized batch assays, the estimated specific rate constants were 0.08, 0.12, 0.083, and 0.084. The data fits well in all the models, with the coefficient of discrimination (R2) ranging from 0.882 to 0.999.


[Studies on the structure of a new ellagic acid glycoside from the root-sprouts of Agrimonia pilosa Ledeb].
Four compounds were isolated from the root-sprouts of Agrimonia pilosa Ledeb. On the basis of physico-chemical properties, spectroscopy (UV, IR, NMR, MS) and chemical degradation, a new compound was elucidated as ellagic acid-4-O-beta-D-xylopyranoside (XV), and three known compounds were identified as agrimonolide (XIII), tormentic acid (XIV), and ellagic acid (XVI).


Homologous and heterologous desensitization of proto-oncogene cfos expression in murine peritoneal macrophages.
Treatment of murine peritoneal macrophages for 30 min with lipopolysaccharide (LPS) resulted in a transient increase in c-fos proto-oncogene mRNA levels (Introna et al., 1986). After 2 h from the initial treatment, c-fos mRNA could no longer be detected and its expression could not be restimulated either by LPS or by other signals including colony stimulating factor-1 (CSF-1) and phorbol myristate acetate (PMA), both of which are able to induce expression of the c-fos gene in unstimulated macrophages. When LPS was removed after an initial 30 min incubation, responsiveness to a second exposure to LPS began to reappear after 3 h and was completely restored by 20 h. The same pattern of desensitization of c-fos induction was observed when CSF-1 stimulated macrophages were subsequently exposed to LPS. The loss of sensitivity to PMA following pretreatment with LPS was selective for c-fos expression as LPS treated macrophages remained responsive to PMA with respect to the ability to stimulate secretion of H2O2. The mechanism of desensitization was localized, at least in part, at the level of transcription as demonstrated by analysis of c-fos transcripts in nuclei isolated from macrophages pretreated and restimulated with LPS.


Spinobulbar neurons in lamprey: cellular properties and synaptic interactions.
An in vitro preparation of the nervous system of the lamprey, a lower vertebrate, was used to characterize the properties of spinal neurons with axons projecting to the brain stem [i.e., spinobulbar (SB) neurons)]. To identify SB neurons, extracellular electrodes on each side of the spinal cord near the obex recorded the axonal spikes of neurons impaled with sharp intracellular microelectrodes in the rostral spinal cord. The ascending spinal neurons (n = 144) included those with ipsilateral (iSB) (63/144), contralateral (cSB) (77/144), or bilateral (bSB) (4/144) axonal projections to the brain stem. Intracellular injection of biocytin revealed that the SB neurons had small- to medium-size somata and most had dendrites confined to the ipsilateral side of the cord, although about half of the cSB neurons also had contralateral dendrites. Most SB neurons had multiple axonal branches including descending axons. Electrophysiologically, the SB neurons were similar to other lamprey spinal neurons, firing spikes throughout long depolarizing pulses with some spike-frequency adaptation. Paired intracellular recordings between SB and reticulospinal (RS) neurons revealed that SB neurons made either excitatory or inhibitory synapses on RS neurons and the SB neurons received excitatory input from RS neurons. Mutual excitation and feedback inhibition between pairs of RS and SB neurons were observed. The SB neurons also received excitatory inputs from primary mechanosensory neurons (dorsal cells), and these same SB neurons were rhythmically active during fictive swimming, indicating that SB neurons convey both sensory and locomotor network information to the brain stem.


Can naloxone prescription and overdose training for opioid users work in family practice? Perspectives of family physicians.
To explore family physicians' attitudes toward prescribing naloxone to at-risk opioid users, as well as to determine the opportunities and challenges for expanding naloxone access to patients in family practice settings. One-hour focus group session and SWOT (strengths, weaknesses, opportunities, and threats) analysis. Workshop held at the 2012 Family Medicine Forum in Toronto, Ont. Seventeen conference attendees from 3 Canadian cities who practised in various family practice settings and who agreed to participate in the workshop. The workshop included an overview of information about naloxone distribution and overdose education programs, followed by group discussion in smaller focus groups. Participants were instructed to focus their discussion on the question, "Could this [overdose education and naloxone prescription] work in your practice?" and to record notes using a standardized discussion guide based on a SWOT analysis. Two investigators reviewed the forms, extracting themes using an open coding process. Some participants believed that naloxone could be used safely among family practice patients, that the intervention fit well with their clinical practice settings, and that its use in family practice could enhance engagement with at-risk individuals and create an opportunity to educate patients, providers, and the public about overdose. Participants also indicated that the current guidelines and support systems for prescribing or administering naloxone were inadequate, that medicolegal uncertainties existed for those who prescribed or administered naloxone, and that high-quality evidence about the intervention's effectiveness in family practice was lacking. Family physicians believe that overdose education and naloxone prescription might provide patients at risk of opioid overdose in their practices with broad access to a potentially lifesaving intervention. However, they explain that there are key barriers currently limiting widespread implementation of naloxone use in family practice settings.


Contrast sensitivity testing: a more complete assessment of vision.
Contrast sensitivity testing is a powerful tool for determining the capability of the visual system to process spatial and temporal information about the everyday objects we see. The current gold standard in the assessment of vision, visual acuity, provides only a limited amount of information, obtained under artificial conditions. Contrast sensitivity testing measures a range of visual performance under real-life conditions. It measures the least amount of contrast needed to detect a visual stimulus and gives us a more complete quantitization of patients' visual capabilities. Many instances in which losses in contrast sensitivity were detected when visual acuity (one point on the contrast sensitivity function) was normal have been reported. These include amblyopia, neuro-ophthalmology, retina, anterior segment disease, and glaucoma. Therefore, contrast sensitivity testing enables the clinician to diagnose selective deficits in visual processing at an earlier stage than is possible with conventional testing methods.


Development of tolerance to the ACTH-releasing effects of beta-endorphin.
Acute intracisternal injection of human beta-endorphin results in increased plasma concentration of adrenocorticotropic hormone (ACTH). Repeated injections of beta-endorphin are associated with the development of tolerance with regard to this ACTH-stimulating effect.


Downregulation of BMI-1 enhances 5-fluorouracil-induced apoptosis in nasopharyngeal carcinoma cells.
5-Fluorouracil (5-FU) is an important chemotherapeutic agent for nasopharyngeal carcinoma (NPC). However, drug resistance may occur after several cycles of 5-FU-based chemotherapy. The oncogene B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been shown to be involved in the protection of cancer cells from apoptosis. In this study, 5-FU treatment could increase the percentage of apoptotic NPC cells among BMI-1/RNAi-transfected cells than that among cells transfected with the empty vector. The 50% inhibitory concentration (IC(50)) values of 5-FU were significantly decreased to a greater extent in the cells transfected with BMI-1/RNAi. Most importantly, the expression of phospho-AKT and the anti-apoptotic protein BCL-2 were downregulated in the cells in which BMI-1 expression was inhibited, whereas the apoptosis-inducer BAX was observed to be upregulated. Abrogation of AKT pathway by a PI3K inhibitor could not further increase the sensitivity to 5-FU in the cells with reduced BMI-1 expression. Taken together, BMI-1 depletion enhanced the chemosensitivity of NPC cells by inducing apoptosis; which is associated with inhibition of the PI3K/AKT pathway.


Multidetector Computed Tomography Findings in Pulmonary Hamartomas: A New Fat Detection Threshold.
The aim of the study was to determine the accuracy of multidetector computed tomography in the evaluation of histologically confirmed pulmonary hamartomas (PHs), with a special focus on fat detection. Data from 55 patients who had received a histologically confirmed diagnosis of PH and had undergone 64-slice thoracic MDCT were retrospectively evaluated. PHs manifested predominantly as peripheral pulmonary nodules with lobulated margins. The average lesion diameter was 1.51 cm (SD 0.6 cm). Histologic analyses identified fat content in 43/55 (78.2%) surgical specimens. The accuracy, sensitivity, and specificity of fat detection at a density threshold of -40 HU were 83.7%, 100%, and 87.2%, respectively. A threshold of -33 HU yielded better results (95.3%, 100%, and 96.3%, respectively). Popcorn-like calcifications were found in only 12/55 (21.8%) PHs and were the only imaging feature suggestive of PH in 7.2% of cases. Most (66%) lesions with popcorn-like calcifications also contained fat. The adoption of a new threshold for fat content (<-33 HU) can lead to further improvements in the overall ability to detect PHs by CT.


Evaluating the efficacy of primary excision and closure for the management of lip leukoderma and introducing the surgical site morbidity score as an effective tool for assessment of postoperative morbidity.
The lips are considered of great importance for the perception of beauty and there is still a lacuna in the attempt to successfully re-pigment resistant areas of vitiligo especially the lips. No technique evolved so far ensures 100% pigmentation with a good cosmetic appearance. To study the efficacy and cosmetic outcome following primary excision and closure in the management of lip vitiligo and assessing postoperative morbidity using the created surgical site morbidity score (SSMS). Twenty-five patients with vitiligo involving the inner margin of lower lips were posted for primary excision and closure of the vitiliginous area. Patients were followed up at 7 days and every 6 months. A SSMS including pain (P), healing time (H), and presence of complications (C) as parameters for assessment of postoperative morbidity were recorded at every follow-up visit. All patients showed healthy lip mucosa within 7 days of the procedure and no recurrence was noted at 24 months of follow up. The postoperative morbidity based on the SSMS was minimal, with a mean score of P2H8C0. Primary excision and closure technique is a safe and inexpensive modality in the management of lip vitiligo with immediate results and excellent cosmetic outcomes.


Ultrathin 2D-MOFs for dual-enzyme cascade biocatalysis with sensitive glucose detection performances.
In recent years, two-dimensional nanosheet metal-organic frameworks (2D MOFs) have been widely considered as promising carriers for enzyme immobilization owing to their large surface area, designable and tunable structures, and other properties that enhance enzyme loading and modulate interactions with enzymes. In this study, a series of ultrathin 2D M-TCPP (M = Co, Ni, Zn, Cu) nanosheets were synthesized employing a surfactant-assisted bottom-up approach, and the effect of solvent ratio on the morphology and properties of 2D MOFs was explored. After systematic characterization, Cu-based 2D MOFs with large specific surface areas and excellent water stability was selected as the carrier for the co-immobilization of glucose oxidase (GOx) and horseradish peroxidase (HRP). The effects of adsorption and covalent immobilization strategies on bis-enzyme loading and enzyme activity, as well as their applications in rapid glucose detection, were systematically investigated. The results showed that A-CTGH and C-CTGH owned enzyme loadings of 187.9 and 249.1 mg/g, respectively, and exhibited superior enzymatic activity when exposed to harsh environments compared to free enzymes. In addition, the covalently immobilized biocatalyst based on GOx demonstrated a more sensitive glucose detection performance, including a wide linear range from 5.0 to 16 μM with a detection limit of 0.6 μM.


Response of bone metabolism related hormones to a single session of strenuous exercise in active elderly subjects.
To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects. Twenty one active elderly subjects (11 men and 10 women; mean age 73.3 years) showing a mean theoretical Vo2max of 151.4% participated. Concentrations of plasma ionised calcium (iCa), serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and 1.25-dihydroxy-vitamin D3 (1.25(OH)2D3), as well as the bone biochemical markers type I collagen C-telopeptide for bone resorption and osteocalcin and bone alkaline phosphatase for bone formation, were analysed before and after a maximal incremental exercise test. At basal level, iPTH was positively correlated with age (r = 0.56, p < 0.01) and negatively correlated with 25(OH)D (r = -0.50; p < 0.01) and 1.25(OH)2D3 (r = -0.47; p < 0.05). Moreover, 25(OH)D and 1.25(OH)2D3 levels were negatively correlated with age (r = -0.50, p < 0.01 and r = -0.53, p < 0.01, respectively). After exercise, iCa and 25(OH)D decreased (p < 0.001 and p = 0.01, respectively) while iPTH increased (p < 0.001). The levels of 1.25(OH)2D3, bone biochemical markers, haematocrit, and haemoglobin were unchanged. The variations in iCa and 25(OH)D were not related to age and/or sex. The iPTH variation was directly related to basal iPTH levels (p < 0.01) and indirectly related to age. In active elderly subjects, strenuous exercise disturbed calcium homeostasis and bone related hormones without immediate measurable effect on bone turnover. Although an increase in iPTH could have an anabolic action on bone tissue, our findings from our short term study did not allow us to conclude that such action occurred.


Emergency departments as under-utilized venues to provide HIV prevention services to female sex workers in Nairobi, Kenya.
Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and remain a key target population for efforts to reduce transmission. While HIV prevention tools such as PEP and PrEP are available through outpatient FSW clinics, these services are underused. Emergency medicine is a rapidly expanding field in Kenya and may provide a novel venue for initiating or optimizing HIV prevention services. This study examined the characteristics of FSW from Nairobi, Kenya, who had utilized an emergency department (ED) during the past year to broaden our understanding of the patient factors related to usage. An anonymous questionnaire was administered to a convenience sample of 220 Nairobi FSW attending dedicated clinics from June to July 2019. The participants were categorized into those who attended an ED over the past year (acute care users) and clinic-only users (control). A modified version of the WHO Violence Against Women Instrument assessed gender-based violence. Multivariable negative binomial logistic regressions evaluated predictors of health care use among these populations. Of the total 220 women (median [IQR] age 32 [27-39]), 101 and 116 were acute care and control populations, respectively. Acute care users had 12.7 ± 8.5 healthcare visits over a 12-month period, and the control population had 9.1 ± 7.0 (p < 0.05). ED attendance did not improve the PrEP usage, with 48.5%, and 51% of acute care and clinic users indicated appropriate PrEP use. Patient factors that correlated with health care utilization among acute care users included client sexual violence (OR 2.2 [1.64-2.94], p < 0.01), PrEP use (OR 1.54 (1.25-1.91), < 0.01), and client HIV status (OR 1.35 (1.02-1.69), p < 0.01). Many FSW at high risk for HIV were not accessing HIV prevention tools despite attending a dedicated FSW clinic offering such services. FSW who had attended an ED over the past year had a higher prevalence of HIV risk factors, demonstrating that emergency departments may be important acute intervention venues to prevent HIV transmission in this population. These results can guide policy design, health care provider training, and facility preparedness to support strategies aimed at improving HIV prevention strategies for FSW in Kenyan ED's.