Measuring numeracy without a math test: development of the Subjective Numeracy Scale.
Basic numeracy skills are necessary before patients can understand the risks of medical treatments. Previous research has used objective measures, similar to mathematics tests, to evaluate numeracy. To design a subjective measure (i.e., self-assessment) of quantitative ability that distinguishes low- and high-numerate individuals yet is less aversive, quicker to administer, and more usable for telephone and Internet surveys than existing numeracy measures. Paper-and-pencil questionnaires. The general public (N = 703) surveyed at 2 hospitals. Forty-nine subjective numeracy questions were compared to measures of objective numeracy. An 8-item measure, the Subjective Numeracy Scale (SNS), was developed through several rounds of testing. Four items measure people's beliefs about their skill in performing various mathematical operations, and 4 measure people's preferences regarding the presentation of numerical information. The SNS was significantly correlated with Lipkus and others' objective numeracy scale (correlations: 0.63-0.68) yet was completed in less time (24 s/item v. 31 s/item, P < 0.05) and was perceived as less stressful (1.62 v. 2.69, P < 0.01) and less frustrating (1.92 v. 2.88, P < 0.01). Fifty percent of participants who completed the SNS volunteered to participate in another study, whereas only 8% of those who completed the Lipkus and others scale similarly volunteered (odds ratio = 11.00, 95% confidence interval = 2.14-56.65). The SNS correlates well with mathematical test measures of objective numeracy but can be administered in less time and with less burden. In addition, it is much more likely to leave participants willing to participate in additional research and shows much lower rates of missing or incomplete data.


The PPARβ/δ-AMPK Connection in the Treatment of Insulin Resistance.
The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.


Small-molecule BET inhibitors in clinical and preclinical development and their therapeutic potential.
Lysine acetylation is a pivotal mechanism in chromatin processes and the regulation of gene transcription. The acetylated lysine residues of histones are exclusively recognized by bromodomains (BRDs) known as epigenetic reader. Proteins containing BRDs undergo a post-translational modification (PTM) with development of cellular signaling and disease biology. The bromo and extra-terminal (BET) proteins are the second subfamily, which play important roles in cellular proliferation, cell cycle progression and chromatin compaction. Recently, a variety of small molecules have been reported to interact with the BET family proteins and accelerate the validation of BET proteins as druggable targets for treatment of cancers, inflammation and related diseases. In this review, we will summarize the small-molecule inhibitors in clinical and preclinical studies of the BET family bromodomains and their medicinal implications.


Cyclosporin A decreases lymphocyte migration to the heart allograft through suppression of their L-selectin expression.
Cyclosporin A (CsA) changes the distribution of the circulating pool of lymphocytes and decreases their traffic to organ allograft. The mechanism of this process is complex and includes, among others, inhibition of induction of nuclear factor of activated T cells and suppression of GM CSF and E-selectin expression. We studied the expression adhesion molecules CD11a, CD18, CD44, CD54 and CD62L on the thoracic duct lymphocytes of rats treated with CsA. The 7-day administration of CsA evidently decreased the expression of CD62L but did not affect the other adhesion molecules. Lower concentration of CD62L molecules on the surface of circulating lymphocytes may influence their migration to allograft and distribution in host lymphoid tissues.


Fear of Falling among Older Patients Admitted to Hospital after Falls in Vietnam: Prevalence, Associated Factors and Correlation with Impaired Health-Related Quality of Life.
Fear of falling (FOF) diminishes older people's independence in daily activities, as well as causes serious health and economic consequences. This study examined the prevalence of FOF in older patients hospitalized due to fall-injuries, its effect on health-related quality of life (HRQOL), and its associated factors. We conducted a cross-sectional study in seven hospitals in Thai Binh, Vietnam. FOF was assessed using a single close-ended question. HRQOL was evaluated by the EQ-5D-5L instrument. Multilevel logistic regression and Tobit regression models were utilized. The prevalence of FOF in 405 older patients admitted to hospitals after fall injuries was 88.2%, with a mean EQ-5D index and EQ-VAS of 0.34 (SD = 0.38) and 61.6 (SD = 15.2), respectively. Factors associated with FOF included living alone (OR = 0.13, 95%CI = 0.04; 0.50.,), history of eye diseases (OR = 4.12; 95%CI = 1.91; 8.89), and experiencing psychological distress (OR= 3.56, 95% CI = 1.05; 12.00). After adjusting for confounders, the EQ-5D index in the FOF group reduced by 0.15 points (Coef. = -0.15; 95%CI= -0.24; -0.05) compared to that of non-FOF group. Our study shows that FOF had an independent negative relationship with HRQOL of patients. Improving knowledge about fall prevention in patients and caregivers could reduce the burden of falls in older people.


Subcellular sequestration of an antigenically unique beta-tubulin.
Tubulin from Trypanosoma brucei was characterized by Western blotting using well defined monoclonal antibodies reacting with alpha- or beta-tubulin and a new monoclonal antibody, 1B41, raised against a microtubule-enriched fraction of T. brucei, which specifically reacts with the beta-subunit of tubulin from either T. brucei or rat brain. This antibody has been used to examine the subcellular distribution of the corresponding antigen in T. brucei by indirect immunofluorescence. The epitope recognized by 1B41 is restricted to a thin line extending from the basal body region to the anterior end of the cell body. To determine the relationship between the immunoreactive zone and the flagellum, double-label immunofluorescence was performed in both interphase and mitotic cells with 1B41 and a flagellar marker, the monoclonal antibody 5E9, specific for the paraflagellar rod polypeptides of trypanosomes. These experiments revealed that the immunoreactive tubulin was contained in a part of the subpellicular cytoskeleton that remained in a constant spatial correspondence with the flagellum throughout the cell division cycle. The beta-tubulin recognized by 1B41 may be segregated into the microtubular structures associated with a cisterna of the endoplasmic reticulum forming the subflagellar microtubule quartet (SFMQ). These results suggest that the presence of an antigenically unique beta-tubulin defines a subpopulation of microtubules possessing specific dynamic properties that may be involved in the morphogenesis of daughter cells during the division of T. brucei.


Hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery: assessment with open-system 1H-MR spectroscopy.
The purpose of this study was to assess, with histopathologic control, the use of open-system 1-T (1)H MR spectroscopy for the evaluation of hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery. Patients underwent (1)H MR spectroscopy (MRS) for the assessment of steatosis before and 3 months after surgery. Liver biopsy was performed during surgery. Hepatic steatosis was expressed as the ratio of fat peak area to cumulative water and fat peak areas. Histopathologic percentage of steatosis was graded as none (0-5%), mild (5-33%), moderate (33-66%), or severe (> 66%). The accuracy of (1)H-MRS and Spearman correlation coefficient were calculated. Differences between groups were assessed with the Wilcoxon signed rank and Mann-Whitney tests. The study included 38 patients (median age, 45.5 years; median body mass index, 47.7). Before surgery, median steatosis measured with (1)H-MRS was 5.8%. The accuracy of (1)H-MRS was 89% (32/36), and the (1)H-MRS findings correlated with the histopathologic assessment of steatosis (r = 0.85, p < 0.001). With (1)H-MRS, no steatosis was discriminated from mild steatosis (p = 0.011), mild was discriminated from moderate steatosis (p < 0.001), and moderate was discriminated from severe steatosis (p = 0.021). Three months after surgery, steatosis had decreased to 3.1% (p < 0.001). The prevalence of hepatic steatosis measured with (1)H-MRS decreased from 53% to 32%. In the care of morbidly obese patients undergoing assessment of hepatic steatosis and changes in steatosis after gastric bypass surgery, (1)H-MRS with an open 1-T MRI system is feasible. Measurements of hepatic fat with (1)H-MRS are accurate and correlate with clinical and histopathologic results.


Synaptic plasticity, a symphony in GEF.
Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, the main structural component of dendritic spines. The ability of neurons to alter spine number and size is essential for the expression of neuronal plasticity. Within spines, guanine nucleotide exchange factors (GEFs) act as critical regulators of the actin cytoskeleton by controlling the activity of Rho-GTPases. In this review we focus on the Rho-GEFs expressed in the nucleus accumbens and localized to the postsynaptic density, and thus positioned to effect rapid alterations in the structure of dendritic spines. We review literature that ties these GEFs to different receptor systems and intracellular signaling cascades and discuss the effects these interactions are likely to have on synaptic plasticity.


Measurement of chloroplast ATP synthesis activity in Arabidopsis.
There are numerous options for monitoring ATP synthesis in chloroplasts using isolated thylakoid membranes, intact chloroplasts, and even whole leaves. Currently, the most commonly used method employs isolated thylakoids coupling the synthesis of ATP to light emission from luciferin in a reaction catalyzed by luciferase. The luciferin-luciferase assay can be highly sensitive and is a direct measure of ATP. Another direct measurement of ATP is the incorporation of 32P into ATP, which, while more technically difficult, has the advantage over the luciferin-luciferase assay of being able to distinguish newly synthesized from total ATP. The phosphorylation of ADP results in a net decrease in pKa (acid disassociation constant) between the reactants and the product ATP, resulting in an increase in the pH of the assay media, which can be used as a convenient, continuous measurement of ATP synthesis. The formation of ΔμH+ across the thylakoid membrane and its concomitant dissipation as ATP is synthesized can be measured by an electrochromic absorption band shift (ECS) of thylakoid pigments measured at 518 nm (Witt, Biochim. Biophys. Acta 505:355-427, 1979; Petty and Jackson, Biochim. Biophys. Acta: Bioenergetics 547:463-473, 1979). The first-order decay time of the ESC can be used to estimate the rate of ATP synthesis providing a noninvasive, indirect method for measuring ATP synthase activity that can be used with intact leaves.


eHCM: Resources Reduction & Demand Increase, cover the gap by a managerial approach powered by an IT solutions.
The economic and financial crisis has also had an important impact on the healthcare sector. Available resources have decreased, while at the same time costs as well as demand for healthcare services are on the rise. This coalescing negative impact on availability of healthcare resources is exacerbated even further by a widespread ignorance of management accounting matters. Little knowledge about costs is a strong source of costs augmentation. Although it is broadly recognized that cost accounting has a positive impact on healthcare organizations, it is not widespread adopted. Hospitals are essential components in providing overall healthcare. Operating rooms are critical hospital units not only in patient safety terms but also in expenditure terms. Understanding OR procedures in the hospital provides important information about how health care resources are used. There have been several scientific studies on management accounting in healthcare environments and more than ever there is a need for innovation, particularly by connecting business administration research findings to modern IT tools. IT adoption constitutes one of the most important innovation fields within the healthcare sector, with beneficial effects on the decision making processes. The e-HCM (e-Healthcare Cost Management) project consists of a cost calculation model which is applicable to Business Intelligence. The cost calculation approach comprises elements from both traditional cost accounting and activity-based costing. Direct costs for all surgical procedures can be calculated through a seven step implementation process.


Functional capacity in severe chronic obstructive pulmonary disease.
To investigate the functional capacity in patients with severe chronic obstructive pulmonary disease (COPD) and healthy subjects. The present study was conducted in the School of Physical Therapy and Rehabilitation, Department of Chest Medicine, Medical School, Hacettepe University, Ankara, Turkey, from June 2002 to July 2003. Forty-five male patients with severe (23 moderately severe, 22 very severe) COPD and 45 healthy controls participated in the study. Pulmonary function tests and 6-minute walk test (6MWT) were performed. The Borg score and heart rate were measured before and after the test. External work of walking was calculated as the product of body weight and walked distance. Functional dyspnea was measured using the modified Medical Research Council (MRC) dyspnea scale. Both distance and external work of 6MWT were significantly lower in severe COPD patients than healthy subjects (p<0.05). No significant differences in distance, external work, and exertional dyspnea were found between moderately severe and very severe COPD patients (p>0.05). Patients with very severe impairment had a significantly lower percentage of predicted 6MWT distance (p<0.05). In these patients, 6MWT distance was correlated significantly with forced expiratory flow in one second (FEV1), MRC score, and Borg score whereas external work of walking correlated with age, FEV1, forced expiratory flow from 25-75%, MRC, and resting Borg score (p<0.05). Severe COPD patients had a significantly impaired functional capacity as compared to their healthy counterparts. Patients with FEV1 <35% have a lower percentage of functional capacity. Both distance and external work of 6MWT are influenced by large and small airway function, level of breathlessness reported during daily activity or scored during an exercise test in patients with FEV1 <35%.


SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection.
New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the C-terminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection.


Sublingual Immunotherapy: Past, present, paradigm for the future? A review of the literature.
Since the early 1900s, allergen immunotherapy has been recognized as an effective treatment option for patients with inhalant allergies. Subcutaneous injection has traditionally been the main route of antigen delivery for immunotherapy in the United States. Over the past 15 years, sublingual administration of allergen extract has become a widely used method of immunotherapy in other countries, particularly in Europe. Although sublingual immunotherapy (SLIT) has been used by some physicians in the United States, this technique has not found widespread utilization. A growing interest in SLIT use in this country is developing. SLIT offers several potential advantages, including excellent safety and tolerability, increased access to immunotherapy, and improved method of antigen delivery to children. This paper reviews the basic and clinical science data available in the literature concerning the immunology, efficacy, and safety of SLIT. It is written to serve as a springboard for future discussions and clinical investigations regarding the potential expanded use of SLIT in the United States.


Severe multicore disease associated with reaction to anesthesia.
Multicore disease is a nonprogressive myopathy. To our knowledge, in all previous cases, the clinical course has been benign with no deaths attributed to it. We describe a patient who presented as a floppy baby and remained weaker throughout his life than any other patients previously described. Biopsy findings were characteristic of multicore disease. However, at age 21/2 years, our patient developed congestive heart failure that was easily controlled with digitalis and diuretics. Shortly after cardiac catheterization, the patient developed a high, unexplained fever and died 26 hours later despite aggressive attempts at resuscitation. Therefore, patients with multicores in skeletal muscle may have severe weakness and may also have a predisposition to complications subsequent to anesthesia.


Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.
The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility.


Family needs of parents of children and youth with cerebral palsy.
Understanding the needs of families of children and youth with cerebral palsy (CP) is important for family-centred services. The aims of this study were to identify: (1) differences in the number and types of family needs expressed by parents based on the age and gross motor function level of their children with CP; (2) the most frequent family needs; and (3) needs that differ on gross motor function level. A total of 501 parents (77.6% mothers) of children and youth with CP completed a modified version of a Family Needs Survey and a demographic questionnaire. Children's gross motor function level was classified using the Gross Motor Function Classification System. Total number of family needs differed based on gross motor function level (P < 0.001) but not age. Parents of children/youth who use wheeled mobility expressed the highest number of family needs, while parents of children/youth who walk without restrictions expressed the fewest needs. Family needs for Information (P= 0.001), Support (P= 0.001), Community Services (P < 0.001) and Finances (P < 0.001) differed based on children's gross motor function level. Over 50% of parents expressed family needs for information on current and future services, planning for the future, help in locating community activities and more personal time. Parents of children and youth who use wheeled mobility were more likely to express the need for help in paying for home modifications, equipment, services and locating sitters, respite care providers and community activities. The gross motor function of children/youth with CP has implications for collaboration with families to identify needs and co-ordinate services. Health professionals have a role to assist families with information needs and locating community services and leisure activities. Family needs for future planning suggest that health professionals should assist families to prepare for key periods in the lives of their children with CP.


Comparative studies of the specificities of -chymotrypsin and subtilisin BPN'. Studies with flexible and 'locked' substrates.
Subtilisin BPN' hydrolysed N-acetyl-l-3-(2-naphthyl)-alanine methyl ester, N-acetyl-l-leucine methyl ester and N-acetyl-l-valine methyl ester, faster than alpha-chymotrypsin. Of eight ;locked' substrates tested, only methyl 5,6-benzindan-2-carboxylate was hydrolysed faster by subtilisin, whereas the other esters were better substrates for chymotrypsin. Compared with the values for chymotrypsin, the stereospecific ratios during the hydrolysis of the optically active locked substrates by subtilisin were decreased by one and two orders of magnitude for bi- and tri-cyclic substrates respectively. The polar groups adjacent to the alpha-carbon atom of locked substrates did not contribute significantly to the reactivity of the more active optical isomers, but had a detrimental effect on the less active antipodes during hydrolysis by both the enzymes. These studies show that the binding site of subtilisin BPN' is longer and broader than that of alpha-chymotrypsin.


Two types of luminescence blinking revealed by spectroelectrochemistry of single quantum dots.
Photoluminescence blinking--random switching between states of high (ON) and low (OFF) emissivities--is a universal property of molecular emitters found in dyes, polymers, biological molecules and artificial nanostructures such as nanocrystal quantum dots, carbon nanotubes and nanowires. For the past 15 years, colloidal nanocrystals have been used as a model system to study this phenomenon. The occurrence of OFF periods in nanocrystal emission has been commonly attributed to the presence of an additional charge, which leads to photoluminescence quenching by non-radiative recombination (the Auger mechanism). However, this 'charging' model was recently challenged in several reports. Here we report time-resolved photoluminescence studies of individual nanocrystal quantum dots performed while electrochemically controlling the degree of their charging, with the goal of clarifying the role of charging in blinking. We find that two distinct types of blinking are possible: conventional (A-type) blinking due to charging and discharging of the nanocrystal core, in which lower photoluminescence intensities correlate with shorter photoluminescence lifetimes; and a second sort (B-type), in which large changes in the emission intensity are not accompanied by significant changes in emission dynamics. We attribute B-type blinking to charge fluctuations in the electron-accepting surface sites. When unoccupied, these sites intercept 'hot' electrons before they relax into emitting core states. Both blinking mechanisms can be electrochemically controlled and completely suppressed by application of an appropriate potential.


Normalization of arterial pressure after barodenervation: role of pressure natriuresis.
Studies in several species have demonstrated that mean arterial pressure (MAP) is normal or only slightly elevated after chronic arterial baroreceptor denervation. We hypothesized that the absence of sustained hypertension after barodenervation was the result of a pressure natriuresis response, secondary to sympathetic vasoconstriction of nonrenal vasculature. To test this hypothesis, MAP, sodium balance (NaBal), and water balance were measured before and after aortic baroreceptor denervation (ABD), sinoaortic denervation (SAD), or sham surgery in conscious rats. MAP was increased 20.0 +/- 3.7 mmHg 1 day after ABD but returned to control by day 3. ABD had no significant effect on daily NaBal or water balance. The responses to SAD were similar to those after ABD, with the exception that a significant natriuresis was observed the first day after SAD. However, this was followed by a significant antinatriuresis on day 2, when MAP was still elevated. By day 3 after SAD, MAP, NaBal, and water balance were not significantly different from control. These results suggest that the normalization of MAP after ABD or SAD is not the result of pressure natriuresis but rather failure to maintain a chronic elevation of sympathetic activity after barodenervation.


A Retrospective Evaluation of a Pilot Youth Community Assessment and Treatment Service.
Targeted, highly accessible early intervention for youths with emerging and complex psychiatric presentations is increasingly needed. The Youth Community Assessment and Treatment Team (YCATT) multidisciplinary service was established to provide intensive intervention for youths in Perth, Australia. The authors conducted a retrospective evaluation to examine YCATT's impact on emergency department (ED) visits, psychiatric inpatient admissions, and provision of care for youths in the transition period between adolescent and adult psychiatric services. Demographic, clinical, and service utilization data for all referrals over the pilot period (2016-2017) were collected and analyzed with descriptive statistics. During the pilot period, 308 referrals were accepted. All referred youths had a trauma history and presented with acute or complex conditions, and most (66%) were between 16 and 18 years old. The admission rate to a psychiatric inpatient unit was <7%. Of 61 youths specifically referred to YCATT as an alternative to psychiatric admission, 90% were successfully diverted from psychiatric or ED admission. After discharge from YCATT, youths had improved scores on the Health of the Nations Outcome Scale and 10-item Kessler Psychological Distress Scale. These findings suggest that YCATT is an accessible and effective service for the population of transition-age youths. It appears that YCATT, in collaboration with other community services, contributed to diverting psychiatric inpatient admissions, facilitated outpatient treatment, and enabled continuity of care for vulnerable youths. The results underscore the need for more accessible, individualized treatment approaches for youths who transition to adulthood.


Risk Factors Associated with Ipsilateral Ischemic Events Following Carotid Endarterectomy for Carotid Artery Stenosis.
Patients undergoing carotid endarterectomy (CEA) are at risk of developing ipsilateral stroke or transient ischemic attacks (TIAs). In this study, we explored factors associated with development of these events following CEA in patients with long-term follow-up. We performed a retrospective analysis of all neurosurgical patients who underwent CEA and presented with ipsilateral ischemic stroke, TIA, or amaurosis fugax. Factors were compared against the outcome variable in univariate analysis. Multivariate logistic regression model was used to identify independent predictive variables. We used Kaplan-Meier analysis (log-rank test) to compare the effect of variables on long-term event-free survival. Our study included 270 patients with an average age of 67.2 years. Two-hundred and forty-nine patients within our study cohort (92.2%) with 273 CEAs were followed at our institution. At presentation, 187 patients (68.5%) were symptomatic. The average follow-up was 50.2 months (113.2 lesion-years). Event-free survival was 91.6% and 89.9% at 2 years and 5 years, respectively. Family history of stroke (P = 0.002), cigarette smoking (P = 0.021), and atrial fibrillation (P = 0.005) significantly increased the risk of adverse events, whereas symptomatic presentation demonstrated a trend toward significance (P = 0.057). A higher risk for ischemic events was observed in female patients as compared with males with asymptomatic presentation (P = 0.005). Our data suggest that family history of stroke, cigarette smoking, and atrial fibrillation are independent risk factors for developing ischemic events after CEA. In patients with asymptomatic presentation, female gender is also a risk factor. Identification of patients at risk is critical for tailored postoperative patient management and patient education.


Attention, communication, and schizophrenia.
The paper starts by drawing the historical lines for and giving an account of the main methods and results from an empirical investigation of cognitive disorders in schizophrenics and communication deviances in their parents. The focus of the report is on the significant correlations that were found between some aspects of parents' style of communication and offsprings' cognitive functioning. On the basis of the empirical study, the relationship between attention and communication is discussed, and the issue of whether attentional processes "change identity" by being embedded in a social context is considered. Furthermore, the influence of deviant communication in parents on attentional processes in offspring is discussed in relation to a main postulate in Vygotsky's theory; namely, that higher mental functions are internalized social relations.


Whole Genome Resequencing from Bulked Populations as a Rapid QTL and Gene Identification Method in Rice.
Most Quantitative Trait Loci (QTL) and gene isolation approaches, such as positional- or map-based cloning, are time-consuming and low-throughput methods. Understanding and detecting the genetic material that controls a phenotype is a key means to functionally analyzing genes as well as to enhance crop agronomic traits. In this regard, high-throughput technologies have great prospects for changing the paradigms of DNA marker revealing, genotyping, and for discovering crop genetics and genomic study. Bulk segregant analysis, based on whole genome resequencing approaches, permits the rapid isolation of the genes or QTL responsible for the causative mutation of the phenotypes. MutMap, MutMap Gap, MutMap+, modified MutMap, and QTL-seq methods are among those approaches that have been confirmed to be fruitful gene mapping approaches for crop plants, such as rice, irrespective of whether the characters are determined by polygenes. As a result, in the present study we reviewed the progress made by all these methods to identify QTL or genes in rice.


Measuring sediment grain size across the catchment to reef continuum: Improved methods and environmental insights.
Sediments collected within freshwater, estuarine and marine habitats were used to trial various chemical and physical pre-treatments to develop a systematic protocol for grain-size analysis using laser diffraction. Application of this protocol mitigates the influence of bio-physical processes that may transform grain-size distributions, enabling the characterisation and quantification of 'primary' mineral sediments across the complex freshwater-marine continuum to be more reliably assessed. Application of the protocol to two Great Barrier Reef (Australia) river catchments and their estuaries reveals the ecologically relevant <20 μm fraction comprises a larger component of exported sediment than existing methods indicate. These findings are highly relevant when comparing measured data to grain-size-specific modelled sediment loads and water-quality targets. Finally, adoption of the protocol also improves the environmental interpretation of the influence of 'terrigenous sediment' in marine settings, including quantification of newly-delivered flood plume sediment.


[Pleural cholesterol: a useful determination].
The difference between exudates and transudates is the first question a clinician must solve when facing a pleural effusion. A great number of parameters have been tried without a definite efficacy of any of them. Cholesterol is an easy, useful determination for distinguishing exudates from transudates. In our series of 86 patients a cholesterol value of 50 mg/dl allowed us to correctly classify 94.2% of effusions. The ratio between pleural fluid cholesterol/serum cholesterol was more efficient because it permitted to correctly classify 97.7% of effusions, in one of those major groups which constitute the binomial exudate/transudate.


[Immunohistochemical detection of lactoferrin of human milk in the tissues of the human and the fetus].
By means of the indirect immunoperoxidase method in deparaffinized slices a comparative investigation on distribution of the female milk lactoferrin (LF) in tissues of the mature person and in the fetus has been performed. LF is revealed in cells of the neutrophil line of the mature person and of the fetus and in the secretory epithelium of some organs of the mature person (in the mammary, submandibular and parotid salivary glands, in the bronchial mucous membrane glands in the fundal and pyloric glands of the stomach). In all the cases investigated LF is revealed in the cells producing serous secrete: in the cells of the serous terminal parts and in the serous semilunar mixed terminal parts of the salivary glands, in the serous cells of the bronchial glands and in the chief cells of the gastric mucous membrane glands. In the fetal secretory epithelium of the organs LF is not found. As LF is revealed in the secretory epithelium of the mature person and is not revealed in the corresponding epithelium of the fetus, it should be considered as a marker of the cells, that reach certain degree of differentiation.


Value of combined XCT/SPECT technology for avoiding false positive planar (123)I-MIBG scintigraphy.
The clinical value of combined XCT/SPECT technology in a single device in patients undergoing (123)I-MIBG scintigraphy was analyzed. 31 patients (19 men, 12 women; mean age 55 years, range: 31-79 years) demonstrating focal accumulation in planar (123)I-MIBG scan were further investigated with a double headed gamma camera with an X-ray tomograph mounted on the same gantry (GE Medical Systems, Millennium VG with Hawkeye, Milwaukee, USA) for anatomical definition of the focal (123)I-MIBG uptake. The patients were referred to (123)I-MIBG scintigraphy because of biochemically (81%) and/or clinically (19%) suspected pheochromocytoma. In 23 out of 31 patients (74%) the fused images demonstrated physiological accumulation (i. e. intestinal, renal) of (123)I-MIBG. In two patients (6%) suspected adrenal MIBG-accumulation was caused by inhomogeneous liver uptake. In two patients (6%) focal abdominal accumulation was correctly localised in the adrenal glands. Furthermore, the differentiation of bone metastasis from a local recurrence for phaeochromocytoma was accurately possible for two patients (6%). Adrenal lesions mimicking liver foci were correctly localised in the remaining two patients (6%). Our study demonstrates the clinical value of XCT/SPECT in a single device in patients demonstrating focal (123)I-MIBG uptake in planar scintigraphy. The combined XCT/SPECT technology provides a higher diagnostic accuracy.


In vivo analysis of heat-shock-protein-70 induction following pulsed laser irradiation in a transgenic reporter mouse.
Induction of heat shock protein (Hsp) expression appears to correlate with a cytoprotective effect in cultured cells and with improved healing of damaged tissues in animal models and in humans. This family of proteins can also serve as indicators of thermal stress in cases of burn injury or surgical procedures that produce heat. Thus, a rapid in vivo readout for induction of Hsp transcription would facilitate studies of Hsp genes and their encoded proteins as mediators of therapeutic effects and as reporters of thermal damage to tissues. We created a transgenic reporter mouse where expression of luciferase is controlled by the regulatory region of the inducible 70 kDa Hsp, and assessed activation of Hsp70 transcription in live animals in response to rapid, high temperature stresses using in vivo bioluminescence imaging (BLI). This model can be used to noninvasively reveal levels of Hsp70 transcription in living tissues, and has utility in studies of the predictive and protective effects of Hsp70 expression, and of various stress responses in tissues.


Bibliometric Analysis of Nursing Informatics Research.
This study aims to provide a bibliometric overview of research at nursing informatics and understand the state in nursing informatics in the last ten years. We used the Web of Science to extract relevant literature published from 2009 to 2018. A total of 455 articles were retrieved and analyzed. The total of the top 5 institutions, countries, journals was discussed. This study will help researchers to understand trends and the situation in nursing informatics research.


[Acquired Horner's syndrome].
Horner's syndrome is characterized by the classic triad of eyelid ptosis, miosis and facial anhidrosis and is caused by an interruption of the oculosympathetic nerve pathway somewhere between its origin in the hypothalamus and the eye. This review is based on own experiences and a discretionary selection of articles found through non-systematic searches in PubMed. Cases from own practice serve as examples. Based on localization of the nerve pathway interruption, a Horner's syndrome is often classified as central, pre- or postganglionic. For the central type the syndrome is associated with other symptoms and signs from the central nervous system. The preganglionic type is most often caused by a tumor or trauma. The postganglionic type is often associated with pain/headache; most frequently it is seen as a consequence of carotid artery dissection or during cluster headache. Anhidrosis is rarely prominent, and in the postganglionic subtype it is virtually absent. Pharmacological tests can be used in diagnostics. Apraclonidine seems to be a good alternative to cocaine to confirm Horner's syndrome. MRI is generally recommended in the evaluation, if necessary with special sequences. The path of the long oculosympathetic fibers is complex and not fully understood. Topographic diagnostics may be challenging, but in most cases a specific cause is identified.


Rare-earth metal-rich antimonides: syntheses, structures, and properties of Tm(3)Sb and Lu(7)Sb(3).
The two most metal-rich lanthanide antimony phases known were obtained from high-temperature solid state syntheses, that for Tm3Sb being of greater difficulty because of its apparent incongruent melting. The Tm3Sb phase crystallizes in the tetragonal space group P42/n (No. 86) with a Ti3P-type (Pearson: tP32) structure, a = 12.2294(5) Angstrom, c = 5.9852(5) Angstrom, and Z = 8. The phase Lu7Sb3 exhibits a Sc7As3-type tetragonal structure, I4/mcm (No. 140) (tI56), with a = 15.5974(7) Angstrom, c = 8.8130(7) Angstrom, and Z = 8. Both structures are described in terms of compact arrays of condensed chains of metal polyhedra (tetrahedral, tetrahedral star, trigonal prismatic, cubic) together with six- to nine-coordinate Sb in metal polyhedra. Magnetic susceptibility data on the paramagnetic Tm3Sb are also reported.


Functional analysis of glycosyltransferase genes from Lactococcus lactis and other gram-positive cocci: complementation, expression, and diversity.
Sixteen exopolysaccharide (EPS)-producing Lactococcus lactis strains were analyzed for the chemical compositions of their EPSs and the locations, sequences, and organization of the eps genes involved in EPS biosynthesis. This allowed the grouping of these strains into three major groups, representatives of which were studied in detail. Previously, we have characterized the eps gene cluster of strain NIZO B40 (group I) and determined the function of three of its glycosyltransferase (GTF) genes. Fragments of the eps gene clusters of strains NIZO B35 (group II) and NIZO B891 (group III) were cloned, and these encoded the NIZO B35 priming galactosyltransferase, the NIZO B891 priming glucosyltransferase, and the NIZO B891 galactosyltransferase involved in the second step of repeating-unit synthesis. The NIZO B40 priming glucosyltransferase gene epsD was replaced with an erythromycin resistance gene, and this resulted in loss of EPS production. This epsD deletion was complemented with priming GTF genes from gram-positive organisms with known function and substrate specificity. Although no EPS production was found with priming galactosyltransferase genes from L. lactis or Streptococcus thermophilus, complementation with priming glucosyltransferase genes involved in L. lactis EPS and Streptococcus pneumoniae capsule biosynthesis could completely restore or even increase EPS production in L. lactis.


Addiction epidemiology in adolescents receiving inpatient psychiatric treatment.
This study sought to characterize adolescent psychiatric inpatient populations from two sites and to determine correlates of substance use disorders (SUD). Screening procedures for SUD differ substantially between these sites. A retrospective review of adolescent inpatients (n=636) revealed that the populations were similar in gender, race and age. Rates of SUD at the site with a formalized SUD screening regimen were higher (39%) than those at the other site (16.5%). Similar correlates of SUD were observed across sites, including older age, legal involvement, sexual activity, childhood disruptive disorder, and tobacco use. These results suggest that SUD is a major issue in adolescent psychiatric patients. More rigorous screening for SUD and its correlates may facilitate earlier detection of substance use in this vulnerable population.


Visual perceptual deficit screening in stroke survivors: evaluation of current practice in the United Kingdom and Republic of Ireland.
Visual perceptual deficits are frequently underdiagnosed in stroke survivors compared to sensory vision deficits or visual neglect. To better understand this imparity, we evaluated current practice for screening post-stroke visual perceptual deficits. We conducted a survey targeted at professionals working with stroke survivors involved in screening visual perceptual deficits across the United Kingdom and the Republic of Ireland. Forty orthoptists and 174 occupational therapists responded to the survey. Visual perceptual deficit screening was primarily conducted by occupational therapists (94%), with 75∼100% of stroke survivors screened per month. Respondents lacked consensus on whether several common post-stroke visual deficits were perceptual or not. During the screening, respondents primarily relied on self-reports and observation (94%), while assessment batteries (58%) and screening tools were underutilised (56%) and selected inappropriately (66%). Respondents reported lack of training in visual perception screening (20%) and physical/cognitive condition of stroke survivors (19%) as extremely challenging during screening. Visual perceptual deficits are screened post-stroke at a similar rate to sensory vision or visual neglect. Underdiagnosis of visual perceptual deficits may stem from both reliance on subjective and non-standardised screening approaches, and conflicting definitions of visual perception held among clinicians. We recommend increased training provision and use of brief performance-based screening tools.IMPLICATIONS FOR REHABILITATIONLack of agreement among clinicians on what constitutes as visual perceptual or sensory vision deficits may prove problematic, as precise and exact language is often required for clinical decision-making (e.g., referrals).Biases for more familiar visual (perceptual) deficits held among clinicians during the screening process may lead to other visual deficits being missed.To avoid problems being missed, clinicians should aim to use standardised assessments rather than stroke survivor self-report and observations of function when screening for visual perceptual difficulties.


A pan-European art trade in the late middle ages: Isotopic evidence on the master of Rimini enigma.
The identity of artists and localisation of workshops are rarely known with certainty before the mid-15th century. We investigated the material used by one of the most prolific and enigmatic medieval sculptors, the Master of the Rimini Altarpiece or Master of Rimini, active around 1420-40. The isotope fingerprints (Sr, S and O) of a representative corpus of masterpieces but also minor artworks, attributed to the Master of Rimini and his workshop, are virtually identical, demonstrating the unity of the corpus and a material evidence behind the stylistic and iconographic ascriptions. The material used is exclusively Franconian (N-Bavarian) alabaster, 600 km distant from the supposed zone of activity of the Master of Rimini workshop according to recent literature. The same material was later used by the prominent Late Medieval German carver Tilman Riemenschneider, active in Würzburg after 1483, whose small corpus of alabaster sculptures we have been able to characterize almost entirely. Based on these findings, we propose here an alternative to the prevailing hypothesis of a Flemish or N-French workshop being founded on similarities of the Rimini sculpture with motives in Flemish and French painting. Our scenario, returning to the initial proposal of a German localisation of the Master of Rimini workshop, assumes the migration of an artist, perhaps trained in the Low Countries or strongly inspired by the Flemish art, to Southern Germany where he founded a highly productive export workshop, well situated on the crossroads of medieval trade, with a pan-European radiance. This study sheds a spotlight on the on the trade networks of luxury goods, the raw material used for their production, and the high-end art market in Europe as well as on international migration of artists and styles, at the eve of the Renaissance.


[Chromosome studies in gynecology].
Clinical indications for chromosome analysis in patients with gynaecological problems are well defined. These include, with primary or secondary amenorrhoea, infertility and repeated miscarriages in adults or retarded puberty and abnormal sexual development in young girls. The type of chromosome abnormality, the incidence, and the management of patients are discussed with reference to 15 years' experience in the Department of Cytogenetics at Tygerberg Hospital. The cytogenetics of 419 patients with amenorrhoea are discussed under headings such as gonadal dysgenesis, monosomy X, chromosome mosaics and the XY female phenotype. Results of chromosome studies in 540 males with a low sperm count are given. The importance of chromosome studies in repeated miscarriages and genetic counselling for carriers of balanced translocations is stressed.


Investigation of the effects of Chlorella vulgaris supplementation in patients with non-alcoholic fatty liver disease: a randomized clinical trial.
To investigate the advantage of Chlorella vulgaris supplementation as an adjunctive therapy in patients with non-alcoholic fatty liver disease (NAFLD). In a randomized, open-label clinical trial, 76 individuals with NAFLD were randomly assigned to: 1) Chlorella group (n=33), receiving C. vulgaris extract (1200 mg/day) + metformin (750 mg/ day) + vitamin E (200 mg/day) for 3 months, or 2) Metformin group (n=43), receiving metformin (1250 mg/ day) + vitamin E (200 mg/day) for 3 months. Weight, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), insulin, total and direct bilirubin, fasting blood sugar (FBS), glycated hemoglobin (HbA1c), uric acid, albumin and lipid profile were evaluated at baseline and at the end of trial. Weight and BMI were decreased in both groups. Serum ALT, AST, triglycerides, uric acid, HbA1c and HOMA-IR index were reduced only in the Chlorella group whereas significant changes in total cholesterol, LDL, HDL and FBS were only observed in the metformin group. There were also borderline significant reductions in insulin and FBS in the Chlorella group. The findings of the present trial indicated that addition of C. vulgaris extract to the therapeutic regimen of NAFLD including metformin and vitamin E, is associated with favorable effects on serum levels of transaminases, triglycerides as well as insulin sensitivity. Therefore, C. vulgaris extract might be a promising hepatoprotective supplement for patients with NAFLD.


Prevalence and predictors of elevated aspartate aminotransferase-to-platelet ratio index in Latin American perinatally HIV-infected children.
Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children. The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1-20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses. APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%-4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ≤ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non-protease inhibitor regimens to 1.5% for protease inhibitor-based regimens. Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor-based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.


Light scattering spectroscopy of human skin in vivo.
We present an in vivo study of the reduced scattering coefficient of normal skin and of common melanocytic nevi in Caucasian subjects. The spectral shape of the reduced scattering coefficient is described well by a power-law dependence on the wavelength, in accordance with previous studies of light scattering by biological tissues. We investigate statistical variations in the scattering spectrum slope and also identify an inherent correlation between scattering intensity and scattering spectral slope, observed mainly in normal skin. In addition, we do not find any significant differences between the scattering properties of normal skin and common melanocytic nevi. Finally, we also provide a short review of previously published studies reporting on the light scattering properties of human skin both in vivo and in vitro.


[Differentiation of hepatic sinusoid vessel cells in rats in the embryonal and postnatal periods of ontogenesis].
Differentiation of the hepatic sinusoidal capillary cells has been studied in the embryonal and postnatal periods of the rat ontogenesis. In the embryonal liver cellular elements are differentiated divergently with formation of endotheliocytes, Kupffer cells and fat-accumulating cells. Differentiation of endotheliocytes is accompanied with their flattening, formation of fenestrae and pores in peripheral processes, increasing amount of micro- and macropinocytic vesicles, and also development of intercellular contacts, presented at first as simple, and then as tight junctions. Formation of intercellular clefts occurs by means of parting of simple junctions; this ensures migration of blood cells across the endothelial lining. Kupffer cells develop out of immature macrophagal elements of the perisinusoidal space. During differentiation they migrate into the endothelial lining. Simultaneously in their cytoplasm lysosomes accumulate and acid phosphatase activity increases. The fat-accumulating cells are formed out of poorly differentiating fibroblast-like elements of the perisinusoidal space. Their differentiation is accompanied with a progressive development of the granular endoplasmic reticulum and with accumulation of reticular fibers in the perisinusoidal space, and in cytoplasm--lipid inclusions.


Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties.
Semax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide. N-terminal amino group acetylation (Ac-Semax) modulates the chemical and biological properties of parental peptide, modifying the ability of Semax to form complex species with Cu(II) ion. At physiological pH, the main complex species formed by Ac-Semax, [CuLH-2]2-, consists in a distorted CuN3O chromophore with a weak apical interaction of the methionine sulphur. Such a complex differs from the Cu(II)-Semax complex system, which exhibits a CuN4 chromophore. The reduced ligand field affects the [CuLH-2]2- formal redox potential, which is more positive than that of Cu(II)-Semax corresponding species. In the amino-free form, the resulting complex species is redox-stable and unreactive against ascorbic acid, unlike the acetylated form. Semax acetylation did not protect from Cu(II) induced toxicity on a SH-SY5Y neuroblastoma cell line, thus demonstrating the crucial role played by the free NH2 terminus in the cell protection. Since several brain diseases are associated either to Cu(II) or Zn(II) dyshomeostasis, here we characterized also the complex species formed by Zn(II) with Semax and Ac-Semax. Both peptides were able to form Zn(II) complex species with comparable strength. Confocal microscopy imaging confirmed that peptide group acetylation does not affect the Zn(II) influx in neuroblastoma cells. Moreover, a punctuate distribution of Zn(II) within the cells suggests a preferred subcellular localization that might explain the zinc toxic effect. A future perspective can be the use of Ac-Semax as ionophore in antibody drug conjugates to produce a dysmetallostasis in tumor cells.


Propagation of truncated Gaussian beams and their application in modeling sharp-edge diffraction.
The two new kinds of truncated Gaussian beams, known as the half and quarter Gaussian beams, are defined as the product of the fundamental Gaussian beam with the Heaviside unit step function. Using the generalized Collins integral, the exact analytical propagation formulas are derived for the truncated Gaussian beams through paraxial optical systems. Combined with the Gaussian beam decomposition method, the truncated Gaussian beams are used to represent the sharp edges of a field after a hard aperture. The modified Gaussian beam decomposition method presented in this work enables the calculation of the diffraction of a given field from a hard aperture with an arbitrary shape. This solves one of the limitations of the conventional Gaussian beam decomposition method, which is its inability to accurately model the diffraction of fields with sharp edges, especially in the near field. The validity and accuracy of the proposed method are demonstrated using a few exemplary diffraction calculations.


Algorithm for Turning Detection and Analysis Validated under Home-Like Conditions in Patients with Parkinson's Disease and Older Adults using a 6 Degree-of-Freedom Inertial Measurement Unit at the Lower Back.
Aging and age-associated disorders such as Parkinson's disease (PD) are often associated with turning difficulties, which can lead to falls and fractures. Valid assessment of turning and turning deficits specifically in non-standardized environments may foster specific treatment and prevention of consequences. Relative orientation, obtained from 3D-accelerometer and 3D-gyroscope data of a sensor worn at the lower back, was used to develop an algorithm for turning detection and qualitative analysis in PD patients and controls in non-standardized environments. The algorithm was validated with a total of 2,304 turns ≥90° extracted from an independent dataset of 20 PD patients during medication ON- and OFF-conditions and 13 older adults. Video observation by two independent clinical observers served as gold standard. In PD patients under medication OFF, the algorithm detected turns with a sensitivity of 0.92, a specificity of 0.89, and an accuracy of 0.92. During medication ON, values were 0.92, 0.78, and 0.83. In older adults, the algorithm reached validation values of 0.94, 0.89, and 0.92. Turning magnitude (difference, 0.06°; SEM, 0.14°) and duration (difference, 0.004 s; SEM, 0.005 s) yielded high correlation values with gold standard. Overall accuracy for direction of turning was 0.995. Intra class correlation of the clinical observers was 0.92. This wearable sensor- and relative orientation-based algorithm yields very high agreement with clinical observation for the detection and evaluation of ≥90° turns under non-standardized conditions in PD patients and older adults. It can be suggested for the assessment of turning in daily life.


Are older women likely to use medicines than older men? (Results from AHAP study).
The health of elderly population in the world has been an important issue in recent century and the use of appropriate or inappropriate medications is challenging among them. The purpose of this study was to assess the pattern of medication in elderly population in Amirkola, northern of Iran. This study was conducted on 1534 elderly subjects who participated in Amirkola Health and Ageing Project (AHAP) in 2013. The number of drugs that was used regardless of their indication in terms of age, level of education, disease, cognitive or depression and social support were recorded and compared in both sexes. The mean number of drugs used in men and women was 2.1±2.45 and 3.59±2.75, respectively (P=0.000). Concurrent use of > 4 drugs was seen in 16.5% of men and in 35.12% of women (P=0.000). The difference for using the number of drugs was significant between sexes with low educational level, but was similar in educated individuals. The use of polypharmacy was associated with the number of concurrent diseases (r=0.58, P=000), cognitive status (r=0.065, P=0.012), social support (r=-0.1, P=0.008), and depression (r=0.273, P=0.000). The results show that the use of polypharmacy in the elderly population in Amirkola is relatively high and they need to be educated. Considering the other indices, this problem highly manifested more in the elderly women.


Implementation of isoniazid preventive therapy in southern Lima, Peru: an analysis of health center characteristics.
Tuberculosis (TB) prevention through the use of preventive treatment is a critical activity in the elimination of TB. In multiple settings, limited staffing has been identified as a barrier to managing preventive treatment for TB contacts. This study aims to determine how health center staffing, service type, and TB caseload affects implementation of isoniazid preventive therapy (IPT) for TB contacts in southern Lima. We conducted an ecological study in 2019 in southern Lima, Peru. Through the review of medical records, we identified contacts of TB patients who initiated IPT during 2016-2018, and who were 0-19 years old, the age group eligible for IPT according to Peruvian guidelines. We assessed bivariate associations between health center characteristics (numbers of physicians and nurses, types of services available, annual TB caseload) and IPT initiation and completion using binomial logistic regression. Among 977 contacts, 69% took more than a week to start IPT and 41% did not complete IPT. For those who successfully completed IPT, 58% did not complete full medical follow-up. There was no significant difference in IPT completion or adherence based on whether health centers had more physicians and nurses, more comprehensive services, or higher TB caseloads. Among contacts, female sex was associated with delay in initiating IPT (P = 0.005), age 5-19 years old was associated with completion of IPT (P = 0.025) and age < 5 years old was associated with completion of clinical evaluations (P = 0.041). There are significant gaps in IPT implementation in health centers of southern Lima, Peru, but insufficient staffing of health centers may not be responsible. Further research is needed to identify how IPT implementation can be improved, potentially through improving staff training or monitoring and supervision.


A comparative model: reaction time performance in sleep-disordered breathing versus alcohol-impaired controls.
Patients with sleep-disordered breathing have reaction time deficits that may lead to catastrophic accidents and loss of life. Although safety guidelines do not exist for unsafe levels of sleepiness, they have been established for unsafe levels of alcohol consumption. Since reaction time performance is altered in both, we prospectively used seven measures of reaction time performance as a comparative model in alcohol-challenged normal subjects with corresponding measures in subjects with sleep-disordered breathing. Institutional Review Board-approved, nonrandomized prospective controlled study. Eighty healthy volunteers (29.1+/-7.5 y of age, 56.3% female subjects) performed four reaction time trials using a psychomotor test at baseline and at three subsequent rising alcohol-influenced time points. The same test without alcohol was given to 113 subjects (47.2+/-10.8 y of age, 19.3% female subjects) with mild to moderate sleep-disordered breathing. Mean blood alcohol concentrations (BACs) in the alcohol-influenced subjects at baseline and three trials were 0, 0.057, 0.080, and 0.083 g/dL. The sleep-disordered subjects had mean respiratory disturbance indices of 29.2 events per hour of sleep. On all seven reaction time measures, their performance was worse than that of the alcohol subjects when BACs were 0.057 g/dL. For three of the measures, the sleep-disordered subjects performed as poorly as or worse than the alcohol subjects when alcohol levels were 0.080 g/dL. These results could not be explained by sex or age differences. The data demonstrate that sleep-disordered subjects in this study (with a mean age of 47 y) with mild to moderate sleep-disordered breathing had worse test reaction time performance parameters than healthy, nonsleepy subjects (with a mean age of 29 y) whose BAC is illegally high for driving a commercial motor vehicle in California. This comparative model points out the potential risks of daytime sleepiness in those with sleep-disordered breathing relative to a culturally accepted standard of impairment.


Inhibins, activins and follistatins: a review.
The study of the regulation of the reproductive process has largely focused on the interplay between endocrine organs, gonads and the brain. The discovery of inhibins, activins and follistatins and elucidation of their actions has emphasised their role in human reproduction. This review discusses various evidences provided for their role as well as their potential uses as clinical markers of reproductive function and pathologies.


ISOLATION, CHARACTERIZATION, AND DISTRIBUTION OF ACID MUCOPOLYSACCHARIDES IN RABBIT LEUCOCYTES.
Acid mucopolysaccharides have been extracted from whole rabbit polymorphonuclear leucocytes and from the cytoplasmic granules of these cells. The leucocyte acid mucopolysaccharides can be separated into two fractions by the solubility of their CPC complexes in solutions of differing salt concentration. One of these fractions appears to be identical with hyaluronic acid; the other appears to be an atypical chondroitin sulfate. On both a dry weight and total protein basis the polymorphonuclear leucocyte granule contains approximately 2.6 times as much acid mucopolysaccharide as does the whole cell. Hyaluronic acid is concentrated in the granules in particular; its function is unknown. These results do not indicate that all lysosomes contain abundant acid mucopolysaccharides, for no detectable carbohydrate of this class could be extracted from lysosome-rich alveolar macrophages.


Learning HMMs for nucleotide sequences from amino acid alignments.
Profile hidden Markov models (profile HMMs) are known to efficiently predict whether an amino acid (AA) sequence belongs to a specific protein family. Profile HMMs can also be used to search for protein domains in genome sequences. In this case, HMMs are typically learned from AA sequences and then used to search on the six-frame translation of nucleotide (NT) sequences. However, this approach demands additional processing of the original data and search results. Here, we propose an alternative and more direct method which converts an AA alignment into an NT one, after which an NT-based HMM is trained to be applied directly on a genome.


Liquefactive necrosis in Coxsackie B encephalitis.
Coxsackieviruses may cause serious illness in infants and children, specifically myocarditis and meningoencephalitis. Central nervous system lesions have been characterized as inflammatory in nature with mononuclear cell infiltration, neuronophagia, and glial nodule formation largely confined to the brain stem and spinal cord. We present two infants with documented Coxsackie B virus infection who also had widespread multifocal areas of liquefaction necrosis unassociated with inflammation. Such areas of bland necrosis, especially in the cerebrum, are unusual in Coxsackie B virus infection, and may provide the morphological substratum of permanent neurologic impairment in children who survive.


Biliary excretion of amphetamine and methamphetamine in the rat.
1. (14)C-labelled amphetamine and methamphetamine were injected into rats cannulated at the bile duct under thiopentone anaesthesia and the output of their metabolites in urine and bile was determined. 2. With amphetamine, 69% of the (14)C was excreted in the urine and 16% in the bile in 24h. The main metabolite in bile was the glucuronide of 4-hydroxyamphetamine. The output of unchanged amphetamine was much greater in cannulated rats than in intact rats. 3. With methamphetamine, 54% of the (14)C appeared in the urine and 18% in the bile. The main metabolite in the bile was the glucuronide of 4-hydroxynorephedrine. The output of amphetamine, a metabolite of methamphetamine, was much greater in cannulated rats than in intact rats. 4. Evidence has been obtained for the enterohepatic circulation of certain amphetamine and methamphetamine metabolites in the rat. 5. Thiopentone anaesthesia appeared to inhibit the ring hydroxylation of amphetamine administered as such or formed as a metabolite of methamphetamine.


Blind test of physics-based prediction of protein structures.
We report here a multiprotein blind test of a computer method to predict native protein structures based solely on an all-atom physics-based force field. We use the AMBER 96 potential function with an implicit (GB/SA) model of solvation, combined with replica-exchange molecular-dynamics simulations. Coarse conformational sampling is performed using the zipping and assembly method (ZAM), an approach that is designed to mimic the putative physical routes of protein folding. ZAM was applied to the folding of six proteins, from 76 to 112 monomers in length, in CASP7, a community-wide blind test of protein structure prediction. Because these predictions have about the same level of accuracy as typical bioinformatics methods, and do not utilize information from databases of known native structures, this work opens up the possibility of predicting the structures of membrane proteins, synthetic peptides, or other foldable polymers, for which there is little prior knowledge of native structures. This approach may also be useful for predicting physical protein folding routes, non-native conformations, and other physical properties from amino acid sequences.


gli, a zinc finger transcription factor and oncogene, is expressed during normal mouse development.
The oncogene GLI is amplified and expressed in some cases of human malignant glioma and undifferentiated childhood sarcoma and is the prototype for a gene family characterized by a highly conserved set of five tandem zinc fingers and a consensus cysteine-histidine link. This zinc finger motif has been shown to bind DNA with sequence specificity and may mediate transcriptional regulation. Since GLI is expressed in embryonal carcinoma cell lines but not in most normal adult tissues and shows significant sequence similarity within its zinc finger domain to cubitus interruptus dominant (ciD), a Drosophila segmentation gene known to be important in the morphogenesis of the posterior portion of each larval segment, we established the temporal and tissue expression patterns of the mouse homologue of human GLI in day 10 through 18 mouse embryos with Northern blotting, reverse transcriptase coupled PCR, and in situ hybridization. gli transcripts were demonstrated on days 10 through 18 of mouse embryonic development as well as in normal adult uterus, brain, testis, and limb. Tissue expression of gli during gestation was demonstrated in Meckel's precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, the ependymal layer of the spinal cord, and the mesoderm of the gastrointestinal tract. Expression persisted throughout gestation in developing bone and cartilage of the extremities, the ribs, and the vertebral bodies, as well as the gastrointestinal tract mesoderm. These findings support a role for gli family genes in normal craniofacial and digital development in mammals first suggested by the demonstration of translocation breakpoints within the GLI3 gene in families with the Greig cephalopolysyndactylyl syndrome and subsequently by reduced gli3 expression in the mouse mutant extra toes. It is surprising that a single gene would be expressed in such a wide range of mesenchymal structures.


RAD-140 Drug-Induced Liver Injury.
Background: RAD-140, one of the novel selective androgen receptor modulators (SARMs), has potent anabolic effects on bones and muscles with little androgenic effect. Despite the lack of approval for its clinical use, RAD-140 is readily accessible on the consumer market. Hepatotoxicity associated with the use of SARMs has only rarely been reported in the literature. Case Report: A 24-year-old male presented with a 2-week history of diffuse abdominal pain, scleral icterus, pruritus, and jaundice. Prior to presentation, he had been taking the health supplement RAD-140 for muscle growth for 5 weeks. He had a cholestatic pattern of liver injury, with a peak total bilirubin of 38.5 mg/dL. Liver biopsy was supportive of a diagnosis of RAD-140-associated liver injury characterized pathologically by intracytoplasmic and canalicular cholestasis with minimal portal inflammation. Symptoms and liver injury resolved after cessation of the offending agent. Conclusion: To date, only select descriptions of the potential hepatoxicity associated with the use of SARMs, including RAD-140, have been published. Given their potential hepatoxicity and ready availability on the consumer market, RAD-140 and other SARMs should be used judiciously and under close clinical supervision until further hepatic safety data become available.


Cross-disorder and disorder-specific deficits in social functioning among schizophrenia and alzheimer's disease patients.
Social functioning is often impaired in schizophrenia (SZ) and Alzheimer's disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive. Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis. As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen's d's 0.81-1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen's d's 0.65-1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen's d's 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p's <0.001), even more so than severity of disease. AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.


Comparing to ingroup and outgroup members: Do we assimilate, contrast, or neither?
Previous work studying social comparisons suggests that people are likely to assimilate to ingroup members (e.g. Ledgerwood & Chaiken, 2007) but can also contrast from ingroup members if outgroup members are present (Blanton, Miller, & Dye, 2002). The present research built upon these findings by including a no-comparison control group to test for true contrast and assimilation effects. Across two studies, women primed with a gender-math stereotype received false feedback about their performance on a math task; and in some conditions, they learned of the performance of ostensible male and/or female co-participants. Relative to a no-comparison control, we did not see evidence of ingroup assimilation in either study. However, in both studies, we found that participants were likely to contrast their self-evaluations away from downward targets, regardless of group membership. This suggests that self-enhancement motivations may be stronger than the drive for ingroup assimilation.


Doctors' working hours and time spent on patient care in the period 1994 - 2014.
There is always a keen interest in the qualitative and quantitative aspects of doctors' working hours. In this study developments are described in terms of total weekly working hours and time spent on direct patient care from 1994 to 2014 by doctors working in different job categories and medical disciplines in Norway. All data has been obtained from LEFO's reference panel of doctors, a near representative sample of approximately 1 600 practising doctors who have been followed up with questionnaires every second year since 1994. In the course of this period, doctors have come off the panel as they retired and new young doctors have been included in replacement. Questions relating to how they spend their time have always featured in the questionnaire. This article is based on data from 1994, 2000, 2006, 2010 and 2014. Response rates were between 67 and 95 %. From 1994 to 2014, total weekly working hours remained the same for all categories of doctors, except those working in academia. Time spent on direct patient care has fallen, but not significantly, for general practitioners, specialists working in private practice and doctors working in academia and administration. Meanwhile, community medical officers and hospital doctors have seen their time spent on patient care fall significantly over the 20-year period. There is however great variation, particularly between the different medical disciplines in hospitals. Differences and changes in the amount of time spent by doctors on direct patient care are caused by both structural and cultural factors relating to the working situation, and not least by a considerable increase in the number of hospital doctors.


Molecular and functional alterations in a mouse cardiac model of Friedreich ataxia: activation of the integrated stress response, eIF2α phosphorylation, and the induction of downstream targets.
Friedreich ataxia (FA) is a neurodegenerative and cardiodegenerative disease resulting from marked frataxin deficiency. The condition is characterized by ataxia with fatal cardiomyopathy, but the pathogenic mechanisms are unclear. We investigated the association between gene expression and progressive histopathological and functional changes using the muscle creatine kinase conditional frataxin knockout (KO) mouse; this mouse develops a severe cardiac phenotype that resembles that of FA patients. We examined KO mice from 3 weeks of age, when they are asymptomatic, to 10 weeks of age, when they die of the disease. Positive iron staining was identified in KO mice from 5 weeks of age, with markedly reduced cardiac function from 6 weeks. We identified an early and marked up-regulation of a gene cohort responsible for stress-induced amino acid biosynthesis and observed markedly increased phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), an activator of the integrated stress response, in KO mice at 3 weeks of age, relative to wild-type mice. Importantly, the eIF2α-mediated integrated stress response has been previously implicated in heart failure via downstream processes such as autophagy and apoptosis. Indeed, expression of a panel of autophagy and apoptosis markers was enhanced in KO mice. Thus, the pathogenesis of cardiomyopathy in FA correlates with the early and persistent eIF2α phosphorylation, which precedes activation of autophagy and apoptosis.


Reliability of lecithin/sphingomyelin ratios in diabetic pregnancy.
Diabetic pregnancy is said to be associated with a delay in pulmonary maturity and significant false-positive rates for the lecithin/sphingomyelin (L:S) ratio. Lecithin/sphingomyelin ratios without routine estimation of phosphatidylglycerol in the management of 102 insulin-dependent diabetics were analyzed to assess whether or not these ratios were mature at 37 weeks and whether or not the method used was reliable. Only two of 102 (1.9%) values were reported at less than 2 to 1 from amniocentesis at 37 weeks' gestation. The incidence of respiratory distress syndrome was zero. The authors concluded that the L:S ratio measured by the method used, is a reliable predictor of lung maturity in diabetic pregnancy and that with strict glucose homeostasis, normal pulmonary maturation occurs by 37 weeks' gestation in diabetic pregnancy.


Epigenetic Evolution of ACE2 and IL-6 Genes: Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates.
The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. These host factors are subjected to epigenetic regulation; therefore, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immuno-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. The findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs. The epigenetic properties ACE2 and IL-6 genes may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups.


Glass hydration: a method of dating glass objects.
A new nondestructive method for dating or authenticating man-made glass is proposed, and the initial results of an exploration of the potential of this method are presented. The method is based on a relation between the age of a glass object and the thickness of the layer of hydrated glass on its surface, with the thickness of this hydrated surface layer being measured by means of the (15)N nuclear resonance depth profiling technique. A qualitative age scale is established for some common 19th- and 20th-century American glass.


[Flow-optimized multianalytical system for haemoanalysis with ion-selective disc and coated glass electrodes (author's transl)].
Using theoretical models based on the low resistance coefficients of variously shaped bodies subjected to a streaming fluid, a flow-optimized multianalytical system was developed for ion-selective disc electrodes and for Na+-, K+- and Ca2+-selective coated glass electrodes. Due to the streamlined configuration of the carrier PVC membrane region, the flow is uncongested and free of dead spaces. This allows a rapid and precise measurement in serum, plasma or heparinized blood. The system was subjected to a durability test.


Fetuin-A decrease induced by a low-protein diet enhances vascular calcification in uremic rats with hyperphosphatemia.
Although dietary phosphate restriction is important for treating hyperphosphatemia in patients with chronic kidney disease, it remains unclear whether a low-protein diet (LPD), which contains low phosphate, has beneficial effects on malnutrition, inflammation, and vascular calcification. The effects of LPD on inflammation, malnutrition, and vascular calcification were therefore assessed in rats. Rats were fed a normal diet or diets containing 0.3% adenine and low/normal protein and low/high phosphate. After 6 wk, serum and urinary biochemical parameters, systemic inflammation, and vascular calcification were examined. The protective effect of fetuin-A and albumin were assessed in cultured vascular smooth muscle cells. Rats fed the diet containing 0.3% adenine developed severe azotemia. LPD in rats fed high phosphate induced malnutrition (decreases in body weight, food intake, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary oxidative stress marker). LPD decreased the serum fetuin-A level and fetuin-A synthesis in the liver and increased serum calcium-phosphate precipitates. A high-phosphate diet increased aortic calcium content, which was enhanced by LPD. Reduced fetal calf serum in the medium of cultured vascular smooth muscle cells enhanced phosphate-induced formation of calcium-phosphate precipitates in the media and calcification of vascular smooth muscle cells, both of which were prevented by fetuin-A administration. Our results suggest that phosphate restriction by restricting dietary protein promotes vascular calcification by lowering the systemic fetuin-A level and increasing serum calcium-phosphate precipitates and induces inflammation and malnutrition in uremic rats fed a high-phosphate diet.


Maturation of Wilms' tumor pulmonary metastases to benign fibromas after therapy.
A 3-year-old girl with Wilms' tumor developed pulmonary metastases 5 months after diagnosis. All but one of the visible lesions disappeared after thoracic irradiation and multiple-agent chemotherapy. Subsequent thoracotomy revealed 17 small nodules in addition to the visible lesion, and all of them proved to be fibromas. It would appear that the Wilms' tumor metastases to the lung were made to mature to benign neoplastic processes after the treatments given.


Val153Met polymorphism of catechol-O-methyltransferase and prevalence of uterine leiomyomata.
The catechol-O-methyltransferase (COMT) gene encodes enzymes that inactivate catechol estrogens and may have a protective role in estrogen-induced tumorigenesis, such as uterine leiomyoma (fibroids). Val158Met is a common single-nucleotide polymorphism of the COMT gene (Ex4-12 G>A; rs4680) that results in a lower activity enzyme, increasing susceptibility to tumorigenesis. The purpose of this study was to evaluate the relation between the COMTVal158Met polymorphism and uterine fibroids. Participants were 972 premenopausal African American (n = 576) and white (n = 396) women from a cross-sectional sample of women in the National Institute of Environmental Health Science's Uterine Fibroid Study. Blood was collected from participants for DNA, and telephone interviews and questionnaires were completed to gather demographic and reproductive history. Prevalence ratios and 95% confidence intervals were estimated using race-specific log-risk regression models. Effect measure modification by age, body mass index, oral contraceptive use, full-term births, smoking, and alcohol use were also evaluated. Distributions of genotypes and fibroid prevalence varied by race. No associations between fibroids and Val158Met were observed among African American or white participants. This study suggests that variation in this polymorphism alone does not affect fibroid prevalence. Additional research is needed to examine other variations and haplotypes within the COMT gene.


Truth and Bias, Left and Right: Testing Ideological Asymmetries with a Realistic News Supply.
The debate around "fake news" has raised the question of whether liberals and conservatives differ, first, in their ability to discern true from false information, and second, in their tendency to give more credit to information that is ideologically congruent. Typical designs to measure these asymmetries select, often arbitrarily, a small set of news items as experimental stimuli without clear reference to a "population of information." This pre-registered study takes an alternative approach by, first, conceptualizing estimands in relation to all political news. Second, to represent this target population, it uses a set of 80 randomly sampled items from a large collection of articles from Google News and three fact-checking sites. In a subsequent survey, a quota sample of US participants (n = 1,393) indicate whether they believe the news items to be true. Conservatives are less truth-discerning than liberals, but also less affected by the congruence of news.


In situ PEGylation of CAR T cells alleviates cytokine release syndrome and neurotoxicity.
Chimeric antigen receptor T (CAR T) cell immunotherapy is successful at treating many cancers. However, it often induces life-threatening cytokine release syndrome (CRS) and neurotoxicity. Here, we show that in situ conjugation of polyethylene glycol (PEG) to the surface of CAR T cells ('PEGylation') creates a polymeric spacer that blocks cell-to-cell interactions between CAR T cells, tumour cells and monocytes. Such blockage hinders intensive tumour lysing and monocyte activation by CAR T cells and, consequently, decreases the secretion of toxic cytokines and alleviates CRS-related symptoms. Over time, the slow expansion of CAR T cells decreases PEG surface density and restores CAR T cell-tumour-cell interactions to induce potent tumour killing. This occurs before the restoration of CAR T cell-monocyte interactions, opening a therapeutic window for tumour killing by CAR T cells before monocyte overactivation. Lethal neurotoxicity is also lower when compared with treatment with the therapeutic antibody tocilizumab, demonstrating that in situ PEGylation of CAR T cells provides a materials-based strategy for safer cellular immunotherapy.


Distribution of viruses associated with particles in waste water.
The distribution of solids-associated viruses in wastewater was studied to determine the effect of treatment processes on viruses associated with solids. Solids less than 0.3 micrometers in diameter were separated from the liquid phase of each sample by using a continuous-flow centrifuge. The percentage of virus associated with solids larger than 0.3 micrometers decreased from 28% in the influent to 3.4% in unchlorinated effluent, and this was accompanied by a 92% decrease in the total concentration of virus. These results indicate that the original solids-associated virus as well as that is secondarily adsorbed to mixed liquor-suspended solids is lost during clarification. The total concentration of virus was reduced by 82% by chlorination, and the percentage of virus associated with solids increased to 7.7% upon chlorination, indicating some protection due to association with particles larger than 0.3 micrometers. When a suspension of fecal particles and a 0.22-micrometers filtrate of a fecal homogenate were sonicated, a threefold increase in virus titer was observed in each. This demonstrated that viruses may be attached to particles smaller than 0.22 micrometers. Thus, small viral aggregates or viruses attached to submicron particles represented the major portion of solids-associated virus in treated sewage.


[Investigating ocular parameters for predicting anomalous vault among phakic intraocular lens patients].
Objective: To analyze the relationships between preoperative ocular parameters and postoperative anomalous vaults, and research their predictive diagnostic value. Methods: In this retrospective case series study, 664 eyes from 332 patients underwent posterior chamber phakic intraocular lens (pIOL) implantation at Shanghai Bright Eye Hospital and Wuxi Huaxia Eye Hospital from November 2020 to November 2021. Preoperative ocular parameters, including spherical equivalent, intraocular pressure, horizontal/vertical ciliary sulcus diameters (HCS/VCS), white-to-white diameters (WTW), corneal steep/flat curvature, central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), and axial length were collected. The pIOL vaults were measured 3 months after surgery. Patients were categorized into low vault group, optimal vault group, and high vault group based on whether the vault fell within the ideal range (250 to 750 μm). Using the optimal vault group as a benchmark, receiver operating characteristic (ROC) curves were drawn for each ocular parameter of the low and high vault groups to analyze diagnostic efficiency and cut-off values for abnormal vaults after pIOL operation. Each ocular parameter was used as an independent variable to establish a multivariate logistic regression model for two different vault anomalies. ROC curves were drawn and analyzed again based on the regression results. Results: Statistically significant differences were observed in WTW, HCS-WTW, ACD, and LT among the three groups. Comparisons between each pair of groups indicated that WTW in the high vault group significantly differed from the other two groups (P<0.05), HCS-WTW in the low vault group significantly differed from the other groups (P<0.05), and ACD and LT explained statistical differences among the three groups (P<0.05), while other parameters showed no differences. ROC curves illustrated that independent ocular parameters such as LT, HCS-WTW, and ACD had clinical predictive diagnostic significance for low vault abnormalities. The area under the curve (AUC), sensitivity, and specificity for these parameters were 0.829(0.952, 0.561), 0.745(0.857, 0.644), and 0.730(0.619, 0.853), respectively. The diagnostic cut-off values were 3.745, 0.020, and 2.975 mm, respectively. The clinical predictive significance of independent ocular parameters in diagnosing the high vault group was poor (AUC<0.7). The predictive Logistic model equation for low vault was Logistic(V1)=-10.067+5.328·HCS-3.620·WTW+6.263·LT, and the predictive model for high vault was Logistic(V2)=6.232+1.323·WTW-3.358·LT. The new parameters in the predictive equation significantly improved the diagnostic efficiency of low and high vault abnormalities, reaching 0.884(0.810, 0.824) and 0.736(0.810, 0.554), respectively. Conclusions: Preoperative predictive diagnostic parameters for postoperative low vault group included LT, HCS-WTW, and ACD, while the high vault group had no independent predictive diagnostic parameters. Logistic regression improved the predictive diagnostic efficiency of abnormal vaults.


Immune responses to tetanus vaccination in Italian healthy subjects and children with recurrent infections.
The ability of vaccine antigen to generate protection is a challenge that cannot be restricted to the antibody response; however, the contribution of T cell-mediated mechanisms has not been extensively analyzed. Age and administration to specific categories of patients, i.e. children with recurrent infections (RI), are some of the factors that might affect the vaccine immune response. We investigated the humoral and cellular response to tetanus toxoid (TT) vaccine in 104 healthy children (HC), 11 newborns and 22 healthy adults to characterize the status of immunity according to age and compared it to 118 RI children. Humoral and cellular responses varied in both groups according to age and doses of TT administered. The prevalence of antibody and cellular response was similar in both cohorts (HC 88 percent and 82 percent versus RI 86 percent and 85 percent), however, TT antibody values were significantly higher in 12-18 months old RI children compared to HC (median: 5 IU/ml vs 1.10 IU/ml) (p = 0.02). The lack of an efficient immune response was observed in 12-15 percent of children from both cohorts. Our data showed that specific antibodies were responsible for early protection, whereas cell-mediated mechanisms may contribute to the generation of long-term immunity after an appropriate vaccine recall. The occurrence of higher TT antibody values in 12-18 months old RI children deserves additional research to determine whether they are caused by different infectious agents and/or by other environmental factors. Clarification of this issue is important for categorizing patients into an optimal vaccine policy.


Prevalence of insomnia for Canadians aged 6 to 79.
This study estimates the prevalence of nighttime insomnia symptoms among Canadians aged 6 to 79, and examines trends over time (2007 to 2015). The study is based on 21,826 respondents from the 2007-to-2015 Canadian Health Measures Survey, a nationally representative, cross-sectional survey. Nighttime insomnia symptoms and duration were self-reported. A 42% increase in nighttime insomnia symptoms was observed for adults aged 18 or older (from 16.8% to 23.8%). The majority of Canadians with insomnia symptoms reported having the symptoms for more than one year. This study also showed nighttime insomnia symptoms to be more prevalent in older age groups, women, those from lower socioeconomic backgrounds, and individuals reporting poor health and quality of life. Efforts toward prevention and intervention strategies could reduce the burden of insomnia symptoms among Canadians.


Reliance on pollinators predicts defensive chemistry across tobacco species.
Defensive traits are typically studied in the context of avoiding antagonists, but may also mediate key interactions with mutualists. Plant chemical defences occur in flowers, suggesting pollinators may be agents of selection on defence. We hypothesised that floral defences would deter pollinators, and therefore, pollinators would select for lower defences in outcrossing than self-pollinating species. We measured pollinator reliance and alkaloid levels in 32 greenhouse-grown Nicotiana species. Using a comparative phylogenetic approach, we found significantly lower nectar, floral and leaf nicotine concentrations in outcrossing than selfing species, with a 15-fold decrease in leaf nicotine levels. Nicotine concentrations were positively correlated across tissues, suggesting that selection against floral defences could constrain the evolution of leaf defences. Thus, pollinators could shape the evolution not only of floral defences but also of defences in other tissues where herbivores have traditionally been considered the dominant agent of selection.