c-Fos activity mapping reveals differential effects of noradrenaline and serotonin depletion on the regulation of ocular dominance plasticity in rats.
The roles of the central noradrenergic and serotonergic system in the activity-dependent regulation of ocular dominance plasticity have been a contentious issue. Using c-Fos activity mapping, we have developed a new, straightforward method to measure the strength of ocular dominance plasticity: the number of c-Fos-immunopositive cells in layer IV of rat visual cortex (Oc1B), ipsilateral to the stimulated eye, is a sensitive and reliable measure of the effects of monocular deprivation. Applying this new method, here we studied the unique modification of the degree of c-Fos expression induced in the visual cortex, in that endogenous noradrenaline (NA) and serotonin (5HT) in the cortex were significantly reduced, respectively by specific pharmacological agents. Intraperitoneal injections of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) and p-chlorophenylalanine (pCPA) selectively impair NA- and 5HT-containing nerve terminals and fibers, respectively. In the visual cortex with strongly reduced NA, the number of c-Fos-immunopositive cells was found remaining significantly decreased in response to stimulation of the deprived eye, while by open eye stimulation the expected increase in c-Fos-immunoreactivity was strongly suppressed, showing values not different from those obtained by monocular stimulation in the normal rats. In contrast, in the visual cortex with strongly reduced 5HT no expected decrease was found in response to stimulation of the deprived eye, while, as is usually the case for the normal animals, a significant increase was still induced in response to open eye stimulation. These findings suggest that the noradrenergic and serotonergic system regulate ocular dominance (OD) plasticity differently: in the NA-depleted cortex the expected increase in c-Fos expression by open eye stimulation was not seen due to strong suppression, whereas in 5HT-depletion, the expected decrease in c-Fos expression was not materialized due to strong suppression. The present findings with c-Fos activity mapping method indicated a novel possibility of the differential regulation of OD plasticity by two types of common monoaminergic systems.


Effect of methyl substitution on the irritancy of dibenz[b,f]1,4-oxazepine(CR).
The irritant properties of 3 methylated derivatives of dibenz[b,f]1,4-oxazepine (CR) have been investigated, using the guinea-pig blepharospasm test and isolated cat eye preparations, and compared with the irritancy of the unsubstituted CR molecule. In both tests, the 11-methyl derivative was non-irritant whereas 3 Me-CR and 9 Me-CR retained some irritancy although both were less potent than CR itself. The possible significance of these results are discussed in relation to earlier biochemical studies.


Water molecule switching heterogeneous proton-coupled electron transfer pathway.
Figuring out the specific pathway of semiconductor-mediated proton-coupled electron transfer (PCET) driven by light is essential to solar energy conversion systems. In this work, we reveal that the amount of adsorbed water molecules determines the photo-induced PCET pathway on the TiO2 surface through systematic kinetic solvent isotope effect (KSIE) experiments. At low water content (<1.7 wt%), the photo-induced single-proton/single-electron transfer on TiO2 nanoparticles follows a stepwise PT/ET pathway with the formation of high-energy H+/D+-O[double bond, length as m-dash]C or H+/D+-O-C intermediates, resulting in an inverse KSIE (H/D) ∼0.5 with t Bu3ArO· and KSIE (H/D) ∼1 with TEMPO in methanol-d 0/d 4 systems. However, at high water content (>2 wt%), the PCET reaction follows a concerted pathway with a lower energy barrier, leading to normal KSIEs (H/D) ≥ 2 with both reagents. In situ ATR-FTIR observation and DFT calculations suggest that water molecules' existence significantly lowers the proton/electron transfer energy barrier, which coincides with our experimental observations.


Using intensive time sampling methods to capture daily suicidal ideation: A systematic review.
There has been an increased emphasis on understanding suicidal thoughts and behaviors as they occur in real-time, resulting in a proliferation of studies utilizing intensive time sampling methods. Given the continued growth in this area, there is a need to synthesize the feasibility of these methods in capturing suicidal ideation at the daily level, in addition to an examination of study factors that may impact suicidal ideation detection, to guide future research. Online databases (i.e., PsychINFO, ERIC, PubMed, MEDLINE) were systematically searched for articles published through December 2020 that assessed suicidal ideation at the daily level. Twenty-six articles presenting data from sixteen independent datasets met inclusion criteria. Across included articles, suicidal ideation detection ranged from approximately 1-92% of participant-completed surveys, with 18-100% of unique study participants reporting suicidal ideation during the study period. Assessment-based factors (i.e., number of daily assessments, duration of daily assessment period) did not appear to be meaningfully associated with suicidal ideation detection rates. Rather, participant characteristics (i.e., baseline suicide risk history, inclusion criteria) were better indicators of a study's ability to capture suicidal ideation at the daily level. Findings highlights the impact of targeting participants with elevated suicide risk at study enrollment.


Detection of an aberrant methylation of CDH4 gene in PCR product by ferrocenylnaphthalene diimide-based electrochemical hybridization assay.
Hybridization behavior of 24-meric and 105-meric single stranded DNAs derived from CDH4 gene related to cadherin cell-adhesive protein was tested with 24-meric DNA probe in a ferrocenylnaphthalene diimide (FND)-based hybridization assay. Hybridization efficiency in this system was also clarified using chronocoulometric (CC) measurement with Hexaammineruthenium (III) probe (RuHx). This is first example to calculate hybridization efficiency of PCR product with a DNA probe immobilized on the electrode. Although hybridization efficiency was really small for the PCR product as expected (20% for 105-meric PCR product), PCR products carrying aberrant methylation were discriminated from the wild one due to the electrochemical signal of FND. It was possible since FND possessed high preference for double stranded DNA, especially on the electrode. When applied to aberrant methylation detection for the fragment of CDH4 gene, this system can discriminate over 0.5 ng μL(-1) sample DNA, which is superior to bisulfite sequencing or MSP and COBRA assays.


Erratic control of breathing during exercise in patients with systemic lupus erythematosus: a pilot-study.
The aim of this study was to provide a comprehensive evaluation of the pattern and timing of breathing during incremental exercise in a sample of women living with systemic lupus erythematosus (SLE). In this cross-sectional study, 20 women with SLE without pulmonary involvement were compared with 20 gender-, body mass index- (BMI), and age-matched healthy individuals. By using a cardiopulmonary incremental exercise test, the following parameters were assessed: tidal volume (VT); breathing frequency (BF); total respiratory time (TOT); inspiratory time (TI); expiratory time (TE); inspiratory time to total time (TI/TOT); mean inspiratory flow (VT/TI); ventilatory equivalent for carbon dioxide (VE/VCO2) and end-tidal carbon dioxide pressure (PETCO2). BF and BF/VT were significantly higher in patients with SLE versus controls, whereas VT, TE, TI and TOT were significantly lower in the former group ( p<0.05). Additionally, patients with SLE presented higher VE/VCO2 and lower PETCO2 than controls ( p<0.05), suggesting a ventilatory inefficiency. We reported compelling evidence of abnormal pattern and timing of breathing during incremental exercise in SLE. Considering that an erratic control of breathing may play an important role in exercise intolerance and fatigue, respiratory exercises emerge as a potential treatment for these symptoms in patients with SLE.


A nosocomial pseudo-outbreak of Mycobacterium xenopi due to a contaminated potable water supply: lessons in prevention.
To determine risk factors for Mycobacterium xenopi isolation in patients following a pseudo-outbreak of infection with the organism. Retrospective cohort analysis of mycobacteriology laboratory specimen records and frequency-matched case-control study of hospital patients. General community hospital. For the case-control study, 13 case patients and 39 randomly selected controls with mycobacterial cultures negative for M xenopi, frequency matched by specimen source, whose specimens were submitted from June 1990 through June 1991. Between June 1990 and June 1991, M xenopi was isolated from 13 clinical specimens processed at a midwestern hospital, including sputum (n = 6), bronchial washings (2), urine (4), and stool (1). None of the patients with M xenopi-positive specimens had apparent mycobacterial disease, although five received antituberculosis drug therapy for a range of one to six months. Specimens collected in a nonsterile manner were more likely to grow the organism than those collected aseptically (3.1% versus 0, relative risk = infinity, P = 0.003). M xenopi isolation was attributed to exposure of clinical specimens to tap water, including rinsing of bronchoscopes with tap water after disinfection, irrigation with tap water during colonoscopy, gargling with tap water before sputum collection, and collecting urine in recently rinsed bedpans. M xenopi was isolated from tap water in 20 of 24 patient rooms tested, the endoscopy suite, and the central hot water mixing tank, but not from water in the microbiology laboratory. The pseudo-outbreak occurred following a decrease in the hot water temperature from 130 degrees F to 120 degrees F in 1989. Maintenance of a higher water temperature and improved specimen collection protocols and instrument disinfection procedures probably would have prevented this pseudo-outbreak.


The role of nutrition, intimate partner violence and social support in prenatal depressive symptoms in rural Ethiopia: community based birth cohort study.
Depression during pregnancy has far-reaching adverse consequences on mothers, children and the whole family. The magnitude and determinants of prenatal depressive symptoms in low-resource countries are not well established. This study aims to describe the prevalence of prenatal depressive symptoms and whether it is associated with maternal nutrition, intimate partner violence and social support among pregnant women in rural Ethiopia. This study is based on the baseline data from a large prospective, community-based, birth cohort study conducted in the South Western part of Ethiopia from March 2014 to March 2016. A total of 4680 pregnant women were recruited between 12 and 32 weeks of gestation. Depressed mood was assessed using the Patient Health Questionnaire (PHQ-9) scale and a cut off of ≥8 was taken to define prenatal depressive symptoms. Data collection was conducted electronically on handheld tablets and submitted to a secured server via an internet connection. Bivariate and multivariate logistic regression analyses were computed using IBM SPSS version 20 software. The community based prevalence of depressive symptoms during pregnancy was 10.8% (95%Confidence Interval (CI): 9.92-11.70). Adjusting for confounding variables, moderate household food insecurity (OR 1.74; 95% CI: 1.31-2.32), severe household food insecurity (OR 7.90; 95% CI: 5.87-10.62), anaemia (OR = 1.30; 95% CI: 1.04-1.61) and intimate partner violence (OR 3.08; 95% CI: 2.23-4.25) were significantly associated with prenatal depressive symptoms. On the other hand, good social support from friends, families and husband reduced the risk of prenatal depressive symptoms by 39% (OR 0.61; 95% CI: 0.50-0.76). Prenatal depressive symptomatology is rather common during pregnancy in rural Ethiopia. In this community based study, household food insecurity, anaemia and intimate partner violence were significantly associated with prenatal depressive symptoms. Good maternal social support from friends, families and spouse was rather protective. The study highlights the need for targeted screening for depression and intimate partner violence during pregnancy. Policies aimed at reducing household food insecurity, maternal anaemia and intimate partner violence during pregnancy may possibly reduce depression.


Monoxenic and axenic cultivation of carrier and patient strains of Entamoeba histolytica.
All of five strains of Entamoeba histolytica, isolated from symptomatic cases of amoebiasis, could be adapted to axenic growth on the TP-S-1 medium of Diamond (1968). Four axenic strains were started from amoeba-Crithidia cultures; one could be axenized directly after isolation from a case of cutaneous amoebiasis. Attempts to monoxenize, resp. axenize strains, isolated from Dutch, asymptomatic carriers, were less successful. Only three out of ten strains could be submitted to bacteria-free growth. These three strains, however, originated probably from a recent case of intestinal amoebiasis. The results, suggesting that highly virulent strains can be easier cultivated bacteria-free than those with low or no virulence, are further discussed. The yield of axenic amoebae per tube fluctuates largely depending on many factors such as the strain, the number of transfers (i.e. degree of establishment), the quality of Panmede liver digest and serum in the TP-S-1 medium, and the care of manipulating the cultures. For optimal growth, a more acid medium was required in an amoeba-Crithidia culture than in an axenic culture. Multinucleated, giant amoebae were frequently observed in axenic cultures.


The effect of estimating chest wall compliance on the work of breathing during exercise as determined via the modified Campbell diagram.
The modified Campbell diagram provides one of the most comprehensive assessments of the work of breathing (Wb) during exercise, wherein the resistive and elastic work of inspiration and expiration are quantified. Importantly, a necessary step in constructing the modified Campbell diagram is to obtain a value for chest wall compliance (CCW). To date, it remains unknown whether estimating or directly measuring CCW impacts the Wb, as determined by the modified Campbell diagram. Therefore, the purpose of this study was to evaluate whether the components of the Wb differ when the modified Campbell diagram is constructed using an estimated versus measured value of CCW. Forty-two participants (n = 26 men, 16 women) performed graded exercise to volitional exhaustion on a cycle ergometer. CCW was measured directly at rest via quasistatic relaxation. Estimated values of CCW were taken from prior literature. The measured value of CCW was greater than that obtained via estimation (214 ± 52 mL/cmH2O vs. 189 ± 18 mL/cmH2O; P < 0.05). At modest-to-high minute ventilations (i.e., 50-200 L/min), the inspiratory elastic Wb was greater and expiratory resistive Wb was lower, when modified Campbell diagrams were constructed using estimated compared with measured values of CCW (P = 0.001). These differences were however small and never exceeded ±5%. Thus, although our findings demonstrate that estimating CCW has a measurable impact on the determination of the Wb, its effect appears relatively small within a cohort of healthy adults during graded exercise.


A polysaccharide of Alloiococcus otitidis, a new pathogen of otitis media: chemical structure and synthesis of a neoglycoconjugate thereof.
Alloiococcus otitidis is a recently discovered Gram-positive bacterium that has been linked with otitis media (middle ear infections). In this study, we describe the structure of a novel capsular polysaccharide (PS) expressed by the type-strain of A. otitidis, ATCC 51267, and the synthesis of a glycoconjugate composed of the capsule PS and bovine serum albumin (BSA). The capsule PS of A. otitidis type-strain was determined to be a repeating trisaccharide composed of 3-substituted N-acetyl-D-glucosamine (GlcpNAc), 6-substituted N-acetyl-D-galactosamine (GalpNAc), and 4-substituted D-glucuronic acid (GlcpA), of which the majority was amidically decorated with L-glutamic acid (Glu): {-->6)-beta-GalpNAc-(1-->4)-[Glup-->6]-beta-GlcpA-(1-->3)-beta-GlcpNAc-(1}n. Monomeric analysis performed on other A. otitidis strains revealed that similar components were variably expressed, but Glu appeared to be a regular constituent in all the strains examined. Due to the suitable presence of GlcpA and Glu, our approach for glycoconjugate synthesis employed a carbodiimide-based strategy with activation of available carboxyl groups by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), which afforded direct coupling between the capsule PS and BSA. Analysis by mass spectrometry indicated that this A. otitidis capsule PS-BSA conjugate was composed of BSA units that carried up to seven capsule PSs. This work represents the first report in the literature describing an A. otitidis cell-surface carbohydrate and the synthesis of a glycoconjugate preparation thereof. Presently, we are formulating plans to immunologically evaluate this A. otitidis glycoconjugate vaccine in animals.


Modified ultrafiltration may not improve neurologic outcome following deep hypothermic circulatory arrest.
Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.


Factors Predictive of Radiographic Progression in Ankylosing Spondylitis.
Using a longitudinal observational cohort of ankylosing spondylitis (AS) patients, we sought to identify progression rates and factors predictive of spinal progression. As a secondary aim, we analyzed the effect of tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression. AS patients who had baseline and follow-up cervical and lumbar radiographs were included in the study. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A change of 2 mSASSS units in 2 years was defined as progression. The characteristics of the study group such as demographic, clinical, laboratory, and treatment history were collected. There were 350 patients in the study. The mean ± SD mSASSS increased from 9.3 ± 15.8 units at baseline to 17.7 ± 21.7 units by the sixth year. Mean ± SD changes in mSASSS between the years 0 to 2, 2 to 4, and 4 to 6 were 1.23 ± 2.68, 1.47 ± 2.86, and 1.52 ± 3.7 units, respectively. Overall, 24.3% of the group progressed over 2 years. Male sex (hazard ratio [HR] 2.46 [95% confidence interval (95% CI) 1.05, 5.76]), the presence of baseline damage (HR 7.98 [95% CI 3.98, 16]), increased inflammatory markers (log C-reactive protein level HR 1.35 [95% CI 1.07, 1.70]), and TNFi use (HR 0.82 [95% CI 0.70, 0.96]) were predictive of radiographic progression. There was a 20% reduction in the rate of progression with TNFi. Male sex, the presence of baseline damage, active disease state, and higher inflammatory markers confer a high risk for disease progression. Treatment with TNFi showed a disease-modifying effect by slowing the rate of radiographic progression.


Quantitative assessment of exposure to fecal contamination in urban environment across nine cities in low-income and lower-middle-income countries and a city in the United States.
During 2014 to 2019, the SaniPath Exposure Assessment Tool, a standardized set of methods to evaluate risk of exposure to fecal contamination in the urban environment through multiple exposure pathways, was deployed in 45 neighborhoods in ten cities, including Accra and Kumasi, Ghana; Vellore, India; Maputo, Mozambique; Siem Reap, Cambodia; Atlanta, United States; Dhaka, Bangladesh; Lusaka, Zambia; Kampala, Uganda; Dakar, Senegal. Assess and compare risk of exposure to fecal contamination via multiple pathways in ten cities. In total, 4053 environmental samples, 4586 household surveys, 128 community surveys, and 124 school surveys were collected. E. coli concentrations were measured in environmental samples as an indicator of fecal contamination magnitude. Bayesian methods were used to estimate the distributions of fecal contamination concentration and contact frequency. Exposure to fecal contamination was estimated by the Monte Carlo method. The contamination levels of ten environmental compartments, frequency of contact with those compartments for adults and children, and estimated exposure to fecal contamination through any of the surveyed environmental pathways were compared across cities and neighborhoods. Distribution of fecal contamination in the environment and human contact behavior varied by city. Universally, food pathways were the most common dominant route of exposure to fecal contamination across cities in low-income and lower-middle-income countries. Risks of fecal exposure via water pathways, such as open drains, flood water, and municipal drinking water, were site-specific and often limited to smaller geographic areas (i.e., neighborhoods) instead of larger areas (i.e., cities). Knowledge of the relative contribution to fecal exposure from multiple pathways, and the environmental contamination level and frequency of contact for those "dominant pathways" could provide guidance for Water, Sanitation, and Hygiene (WASH) programming and investments and enable local governments and municipalities to improve intervention strategies to reduce the risk of exposure to fecal contamination.


Better outcomes and reduced failures for arthroplasty over osteotomy for advanced compartmental knee osteoarthritis in patients older than 50 years.
Both compartmental knee arthroplasty (CKA) and open-wedge high tibial osteotomy (HTO) may be used to treat patients older than 50 years of age with advanced compartmental osteoarthritis (OA) secondary to leg axis deformities. A meta-analysis was conducted to clarify the role of open-wedge HTO versus CKA for patients older than 50 years with advanced compartmental knee OA. The present investigation aimed to analyse the clinical outcomes, implant failure and survivorship. This meta-analysis was performed in accordance with the PRISMA guidelines. In September 2020, the main online databases were accessed. All clinical trials comparing the outcomes of open-wedge HTO versus CKA for compartmental knee OA were considered. Data analysis was performed through the Review Manager Software 5.3 (the Nordic Cochrane Collaboration, Copenhagen). Implant survivorship was analysed with a Kaplan-Meier (KM) curve that was performed using the STATA/MP software (StataCorp, College Station, TX). Data from 618 (HTO, 307; CKA, 311) patients were collected. Good baseline comparability among patient age, BMI and gender was detected. The Tegner Activity Scale was higher in the CKA group (P = 0.04), as were the Lysholm score (P = 0.001), the International Knee Documentation Committee (P = 0.0001) and the Knee injury and Osteoarthritis Outcome Score (P = 0.05). At a mean follow-up of 5 years, revisions were less in the CKA cohort (OR, 2.27; P = 0.004). The Kaplan-Meier curve evidenced longer implant survivorship in favour of the CKA group (P = 0.01). In patients older than 50 years of age with compartmental knee OA secondary to frontal axis leg deformities, CKA performed better than open-wedge HTO.


90-Day repeated-dose toxicity study of licorice flavonoid oil (LFO) in rats.
Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of licorice hydrophobic polyphenols in medium-chain triglycerides (MCT). As part of a safety evaluation, a 90-day oral toxicity study in rats was conducted using an LFO concentrate solution (2.90% glabridin). Male and female animals were assigned to one of 12 groups (10 males or females per group) and received corn oil (negative control), MCT (vehicle control), or 400, 600, 800 or 1600 mg/kg of the LFO concentrate solution. In conclusion, LFO concentrate solution induced an anticoagulation effect in both sexes, although there was a clear sex difference. Based on these findings, it is concluded that the no-observed-adverse-effect level (NOAEL) for the LFO concentrate solution is estimated to be 800 mg/kg/day for female rats, and approximately 400 mg/kg/day for male rats.


Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.
A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.


Detoxification system for inorganic arsenic: transformation of As2O3 into TMAO by vitamin B12 derivatives and conversion of TMAO into arsenobetaine.
A new two-step synthetic pathway developed for the transformation of arsenic trioxide [iAs(III); As(2)O(3)] into arsenobetaine (AB; Me(3)As(+)CH(2)CO(2)(-)) involves treatment of iAs(III) with native B(12) or biomimetic B(12) in the presence of glutathione (GSH) to give TMAO with a high selectivity and a high conversion rate; subsequent treatment of TMAO with iodoacetic acid in the presence of GSH gives arsenobetaine.


Illusory posttraumatic growth is common, but genuine posttraumatic growth is rare: A critical review and suggestions for a path forward.
Over the last 2.5 decades, trauma researchers have increasingly become interested in posttraumatic growth (PTG) - the concept that some people experience growth as a result of trauma exposure. I begin by reviewing extant research on PTG, with a focus on measurement and conceptual issues. Expanding on arguments made by others, I distinguish between three forms of PTG, 1) perceived PTG, which is an individual's beliefs about their own PTG, 2) genuine PTG, which is veridical growth following adversity, and 3) illusory PTG, which is motivated fabrications of PTG. Perceived PTG is extremely common, as over half of individuals exposed to a potentially traumatic event (PTE) report moderate or greater levels of PTG. I review evidence that most self-reports of PTG are greatly exaggerated and argue that perceived PTG is mostly illusory PTG. I propose five reasons for the disconnect between perceived PTG and genuine PTG, including design flaws in the current measurements, emotional biases that favor perceived PTG, the inherent appeal of PTG, cultural expectations, and problems of definition. I then review the empirical evidence concerning the prevalence rate of genuine PTG, coming to the bold conclusion that the occurrence of genuine PTG is very rare, contradicting current fundamental beliefs about PTG. I recommend researchers focus on the key areas of measurement and etiology of genuine PTG, which are necessary to create interventions that foster genuine PTG. I conclude by outlining a path to steer the scientific progression of PTG back in the right direction.


Photosynthetic responses of native and introduced C4 grasses from Venezuelan savannas.
Introduced African grasses are invading the grasslands of the Venezuelan savannas and displacing the native grasses. This work, which is part of a program to understand the reasons for the success of the African grasses, specifically investigates whether introduced and native grasses differ in some photosynthetic characteristics.The responses to photon flux density, leaf temperature, leaf-air vapour pressure difference and leaf water potential of leaf photosynthetic rate of two introduced African C4 grasses (Hyparrhenia rufa and Melinis minutiflora) and of a lowland and a highland population of a native Venezuelan grass (Trachypogon plumosus) grown under controlled conditions were compared. These responses in all three species were typical of tropical C4 pasture grasses. The introduced grasses had higher maximum leaf conductance, net photosynthetic rates, and optimum temperature (H. rufa only) for photosynthesis than T. plumosus. However, T. plumosus was able to continue photosynthesis to lower leaf water potentials than the two introduced grasses, and the efficiency which it utilized water, light and mineral nutrients to fix carbon were similar to those of the introduced grasses.The higher rates of leaf photosynthesis of the introduced grasses contributed to, but only partially explained, the higher growth rates compared to T. plumosus. The higher growth rates and nutrient concentration of the introduced grasses are consistent with their ability to establish rapidly, compete successfully for resources, and displace T. plumosus from moist, fertile sites. Conversely, the slower growth rate, lower nutrient concentrations, and superior water relations characteristics are consistent with the capacity of T. plumosus to resist invasion by introduced grasses in poorer sites.


Habitat odor can alleviate innate stress responses in mice.
Predatory odors, which can induce innate fear and stress responses in prey species, are frequently used in the development of animal models for several psychiatric diseases including post-traumatic stress disorder (PTSD) following a life-threatening event. We have previously shown that odors can be divided into at least three types; odors that act as (1) innate stressors, (2) as innate relaxants, or (3) have no innate effects on stress responses. Here, we attempted to verify whether an artificial odor, which had no innate effect on predatory odor-induced stress, could alleviate stress if experienced in early life as a habitat odor. In the current study, we demonstrated that the innate responses were changed to counteract stress following a postnatal experience. Moreover, we suggest that inhibitory circuits involved in stress-related neuronal networks and the concentrations of norepinephrine in the hippocampus may be crucial in alleviating stress induced by the predatory odor. Overall, these findings may be important for understanding the mechanisms involved in differential odor responses and also for the development of pharmacotherapeutic interventions that can alleviate stress in illnesses like PTSD.


Management of ureteroscopic injuries.
Ureteroscopy is an important technique in the management of calculous disease and ureteral lesions but it appears to have a greater potential for injury than percutaneous nephroscopy. In 2 years 4 patients with severe ureteroscopic injuries were treated. In 3 patients complete obstruction of the ureter occurred, and 1 had a major ureteral tear, prolonged urinary extravasation and infection. Even in the presence of total ureteral occlusion patients with short strictures were managed successfully percutaneously but the 2 patients with longer strictures were not. Previous surgery on the ureter or pelvic surgery and radiation therapy appear to be negative factors that affect adversely the ureteral blood supply, and potentiate poor healing and scarring. Nephrostomy tube drainage and ureteral stenting after ureteral dilation appear to be important steps in the percutaneous management of these patients.


The caffeine-sensitive Ca2+ store in bovine adrenal chromaffin cells; an examination of its role in triggering secretion and Ca2+ homeostasis.
The effect of caffeine on catecholamine secretion and intracellular free Ca2+ concentration [( Ca2+]i) in bovine adrenal chromaffin cells was examined using single fura-2-loaded cells and cell populations. In cell populations caffeine elicited a large (approximately 200 nM) transient rise in [Ca2+]i that was independent of external Ca2+. This rise in [Ca2+]i triggered little secretion. Single cell measurements of [Ca2+]i showed that most cells responded with a large (greater than 200 nM) rise in [Ca2+]i, whereas a minority failed to respond. The latter, whose caffeine-sensitive store was empty, buffered a Ca2+ load induced by a depolarizing stimulus more effectively than those whose store was full. The caffeine-sensitive store in bovine chromaffin cells may be involved in Ca2+ homeostasis rather than in triggering exocytosis.


Typeface Reveals Spatial Economical Patterns.
Understanding the socioeconomic and demographic characteristics of an urban region is vital for policy-making, urban management, and urban planning. Auditing socioeconomic and demographic patterns traditionally entails producing a large portion of data by human-participant surveys, which are usually costly and time consuming. Even with newly developed computational methods, amenity characteristics such as typeface, color, and graphic element choices are still missing at the city scale. However, they have a huge impact on personalized preferences. Currently, researchers tend to use large-scale street view imagery to uncover physical and socioeconomic patterns. In this research, we first propose a framework that uses deep convolutional neural network to recognize the typeface from street view imagery in London. Second, we analyze the relationship between 11 typefaces and the average household income in 77 wards of London. The result show that the typefaces used in the neighborhood are highly correlated with economic and demographic factors. Typeface could be an alternative metric to evaluate economic and demographic status in large-scale urban regions. More generally, typeface can also act as a key visual characteristic of a city.


Re-examination of small intestinal disposal of Vibrio cholerae in mice.
The rapid disposal of antibody-treated vibrios by peristalsis in whole animal models makes it difficult to obtain clear evidence for a simultaneous intra-intestinal bactericidal effect. In this paper we have re-examined the evidence for direct intra-intestinal killing. We have found that the data can be explained adequately by peristaltic effects without postulating a direct bactericidal action in vivo.


A comparative review and computational assessment of acetochlor toxicity in fish: A novel endocrine disruptor?
Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, neither immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.


Tuberculosis associated with gastrectomy.
We describe the incidence and clinical features of patients with tuberculosis who had undergone gastric resection in our hospital. A total of 26 patients with tuberculosis who had undergone gastric resection were studied. The prevalence of gastrectomy among patients with tuberculosis was 8.0% (7/87) in 2000, 5.1% (4/78) in 2001, and 13.2% (10/76) in 2002. The average 3-year incidence was 9.1%. The patients' body mass indexes (BMIs) were below 18 kg/m2 in 9 of the 21 patients in whom it was possible to determine BMI and above 22 kg/m2 in only 2 of these 21 patients. Analysis of impaired glucose tolerance revealed oxyhyperglycemia or diabetes mellitus as one risk factor for the development of tuberculosis. Furthermore, poor nutrition among patients who have undergone gastrectomy may provide prognostic information for the development or reactivation of tuberculosis. In Japan, a fairly large percentage of elderly people have undergone gastrectomy for gastric cancer or gastric ulcer, and many have a past history of tuberculosis. Gastrectomy may be a risk factor for the reactivation of tuberculosis.


New basidiomycetous yeasts from southern Africa. II. Sterigmatomyces wingfieldii sp.n.
A new, insect-associated species of the emended genus Sterigmatomyces, St. wingfieldii, is described. A key to the emended genus is given.


High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis.
PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT-PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively. The expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P < 0.05). High PPFIA1 expression was closely related to several clinicopathological characteristics, including tumor location, histological grade, tumor invasion depth, lymph node metastasis, and tumor-node-metastasis (TNM) stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic factor of overall survival in ESCC patients (GSE53625 dataset, P = 0.019; cDNA array dataset, P < 0.001; TMA dataset, P = 0.039). Downregulation of PPFIA1 expression can significantly reduce the migration and invasion ability of ESCC cells. PPFIA1 is related to the migration and invasion of ESCC cells, and can be used as a potential biomarker to evaluate the prognosis of ESCC patients.


Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study.
Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies. This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies. A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017). Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.


The vitamin E-binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis.
The objective of this case-control study of 242 reproductive-age women was to determine the concentration of afamin in the serum and peritoneal fluid of women with and without endometriosis and to test afamin as a diagnostic marker of endometriosis. Afamin levels were altered significantly in the peritoneal fluid of women with endometriosis compared with disease-free controls, correlated with vitamin E levels, and are consistent with increased oxidative stress in the peritoneal cavity of women with endometriosis.


The long-distance psychiatric patient in the emergency room. Insights regarding travel and mental illness.
This paper deals with the motivational, demographic and clinical characteristics of individuals who seek psychiatric help at facilities located a great distance from their places of residence. The study identifies two subgroups within this category. The first (Intentional or Type A) group is constituted by persons who, owing to their concerns with the social stigma of mental illness, or driven by the desire for a magical solution to their problems, purposely undertake the journey to a distantly located psychiatric center. The second (Incidental or Type B) group consists of vacationers, hitch-hikers and skid-row individuals. While these "long distance patients" (LDP) did not show any differences when compared with the remainder of clinic attendance on demographic variables, distinct clinical features differentiated the two populations. Most significantly the LDP had a higher incidence of schizophrenia and alcohol related problems. The difference was entirely accounted for by the Type B subgroup ((LDP less than 0.01; Type A, NS; Type B less than 0.001). Implications of this finding have been discussed in view of the suggested relationships between travel and mental illness. Administrative problems of the LDP have been briefly commented upon.


Hypoglycemia does not affect gonadotroph responsiveness to gonadotropin-releasing hormone in rhesus monkeys.
Hypoglycemia inhibits gonadotropin secretion in primates by an undefined mechanism. Some evidence suggests that hypoglycemia inhibits gonadotropin secretion independent of gonadotropin-releasing hormone (GnRH) inhibition. To this end, the effect of insulininduced hypoglycemia on the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to graded doses of GnRH (25, 75, and 250 ng/kg) administered at 120-min intervals was determined in rhesus monkeys. A crossover design was employed such that each animal received GnRH under both hypoglycemic and euglycemic conditions. Experiments were performed in the follicular phase. Gonadotroph responsiveness to GnRH was quantified by determining the change in area under the LH (DeltaAULHC) and FSH (DeltaAUFSHC) curves that occurred in the first 60 min following each GnRH pulse. There was no statistical difference in DeltaAULHC between euglycemic and hypoglycemic animals at any GnRH dose (25 ng/kg: p = 0.19; 75 ng/kg: p = 0.41; 250 ng/kg: p = 0.46). Similarly, changes in AUFSHC following GnRH administration were comparable in euglycemic and hypoglycemic animals (25 ng/kg: p = 0.59; 75 ng/kg: p = 0.90; 250 ng/kg: p = 0.33). We conclude that hypoglycemia had no effect on gonadotroph responsiveness to GnRH. These results are consistent with the conclusion that hypoglycemia inhibits gonadotropin secretion by acting primarily at the level of the hypothalamus to reduce GnRH secretion rather than affecting pituitary responsiveness to GnRH.


Covalent immobilization of biomolecules on stent materials through mussel adhesive protein coating to form biofunctional films.
It is widely accepted that surface biofunctional modification may be an effective approach to improve biocompatibility and confer new bioactive properties on biomaterials. In this work, mussel adhesive protein (MAP) was applied as a coating on 316 L stainless steel substrates (316 L SS) and stents, and then either immobilized VEGF or CD34 antibody were added to create biofunctional films. The properties of the MAP coating were characterized by scanning electron microscope (SEM), atomic force microscope (AFM) and a water contact angle test. Universal tensile testing showed that the MAP coating has adequate adhesion strength on a 316 L stainless steel material surface. Subsequent cytotoxicity and hemolysis rate tests showed that the MAP coatings have good biocompatibility. Moreover, using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysulfosussinimide (EDC/NHS) chemistry, VEGF and CD34 antibody were immobilized on the MAP coatings. The amount and immobilized yield of VEGF on the MAP coatings were analyzed by enzyme-linked immuno-assays (ELISA). Finally, an endothelial cells culture showed that the VEGF biofunctional film can promote the viability and proliferation of endothelial cells. An in vitro CD34+ cells capturing test also verified the bioactive properties of the CD34 antibody coated stents. These results showed that the MAP coatings allowed effective biomolecule immobilization, providing a promising platform for vascular device modification.


Modeling the dry-weather tidal cycling of fecal indicator bacteria in surface waters of an intertidal wetland.
Recreational water quality at beaches in California and elsewhere is often poor near the outlets of rivers, estuaries, and lagoons. This condition has prompted interest in the role of wetlands in modulating surface water concentrations of fecal indicator bacteria (FIB), the basis of water quality standards internationally. A model was developed and applied to predict the dry-weather tidal cycling of FIB in Talbert Marsh, an estuarine, intertidal wetland in Huntington Beach, California, in response to loads from urban runoff, bird feces, and resuspended sediments. The model predicts the advection, dispersion and die-off of total coliform, Escherichia coli, and enterococci using a depth-integrated formulation. We find that urban runoff and resuspension of contaminated wetland sediments are responsible for surface water concentrations of FIB in the wetland. Model predictions show that urban runoff controls surface water concentrations at inland sites and sediment resuspension controls surface water concentrations near the mouth. Direct wash-off of bird feces into the surface water is not a significant contributor, although bird feces can contribute to the sediment bacteria load. The key parameters needed to accurately predict FIB concentrations, using a validated hydrodynamic model, are: the load due to urban runoff, sediment erodibility parameters, and sediment concentrations and surface water die-off rates of enteric bacteria. In the present study, literature values for sediment erodibility and water column die-off rates are used and average concentrations of FIB are predicted within 1/2 log unit of measurements. Total coliform are predicted more accurately than E. coli or enterococci, both in terms of magnitude and tidal variability. Since wetland-dependent animals are natural sources of FIB, and FIB survive for long periods of time and may multiply in wetland sediments, these results highlight limitations of FIB as indicators of human fecal pollution in and near wetlands.


Cerebral palsy in Victoria: motor types, topography and gross motor function.
To study the relationships between motor type, topographical distribution and gross motor function in a large, population-based cohort of children with cerebral palsy (CP), from the State of Victoria, and compare this cohort to similar cohorts from other countries. An inception cohort was generated from the Victorian Cerebral Palsy Register (VCPR) for the birth years 1990-1992. Demographic information, motor types and topographical distribution were obtained from the register and supplemented by grading gross motor function according to the Gross Motor Function Classification System (GMFCS). Complete data were obtained on 323 (86%) of 374 children in the cohort. Gross motor function varied from GMFCS level I (35%) to GMFCS level V (18%) and was similar in distribution to a contemporaneous Swedish cohort. There was a fairly even distribution across the topographical distributions of hemiplegia (35%), diplegia (28%) and quadriplegia (37%) with a large majority of young people having the spastic motor type (86%). The VCPR is ideal for population-based studies of gross motor function in children with CP. Gross motor function is similar in populations of children with CP in developed countries but the comparison of motor types and topographical distribution is difficult because of lack of consensus with classification systems. Use of the GMFCS provides a valid and reproducible method for clinicians to describe gross motor function in children with CP using a universal language.


Determination of dissociation constants of protein ligands by thermal shift assay.
The thermal shift assay (TSA) is a powerful tool used to detect molecular interactions between proteins and ligands. Using temperature as a physical denaturant and an extrinsic fluorescent dye, the TSA tracks protein unfolding. This method precisely determines the midpoint of the unfolding transition (Tm), which can shift upon the addition of a ligand. Though experimental protocols have been well developed, the thermal shift assay data traditionally yielded qualitative results. Quantitative methods for Kd determination relied either on empirical and inaccurate usage of Tm or on isothermal approaches, which do not take full advantage of the melting point precision provided by the TSA. We present a new analysis method based on a model that relies on the equilibrium system between the native and molten globule state of the protein using the van't Hoff equation. We propose the Kd can be determined by plotting Tm values versus the logarithm of ligand concentrations and fitting the data to an equation we derived. After testing this procedure with the monomeric maltose-binding protein and an allosterically regulated homotetrameric enzyme (ADP-glucose pyrophosphorylase), we observed that binding results correlated very well with previously established parameters. We demonstrate how this method could potentially offer a broad applicability to a wide range of protein classes and the ability to detect both active and allosteric site binding compounds.


Psychological support needs of patients with head and neck cancer and their caregivers: A qualitative study.
The aim of this study was to explore the psychological support needs of patients with head and neck cancer (HNC) and their caregivers. The appropriate timing, length, format and content of sessions were also investigated. Eighty-three patients with HNC and 73 of their caregivers completed questionnaires at diagnosis. Follow-up questionnaires were mailed to patients six months later. Free text-comments to open-ended questions in the questionnaires were analysed using an inductive thematic approach with coding and theme development directed by the content of responses. This was used to determine psychological support needs both at diagnosis and at six month follow-up. Patients described 'just being there', empathy, maintaining normality and practical support as helpful from family/friends. They desired information, honesty, positivity and empathy from clinical staff. Formal psychological support was desired by approximately 40% of patients and caregivers, particularly early after diagnosis and during treatment. Most participants desired face to face sessions, providing individualised information and coping strategies. The results of this study suggest that psychological interventions for patients with HNC and their caregivers should be delivered early after diagnosis in face to face sessions, presenting honest and factual information about the disease and coping strategies.


Vagus nerve stimulation for treatment of epilepsy in Rett syndrome.
This case series presents the outcomes of seven females with Rett syndrome and medically refractory epilepsy who were treated with adjunctive vagus nerve stimulation (VNS) therapy for a minimum of 12 months. Patients ranged in age from 1 to 14 years (median age 9 y) at the time of implantation, had experienced seizures for a median period of approximately 6 years, and had failed at least two trials of antiepileptic drugs before receiving VNS. The median number of seizures per month was 150 (range 12-3600). At 12 months, six females had >or=50% reduction in seizure frequency. VNS was safe and well tolerated, with no surgical complications and no patients requiring explantation of the device. Quality of life outcomes of note among these patients included reports at 12 months of increased alertness among all seven patients. No change in mood or communication abilities was noted.


Allergen Immunotherapy Outcomes and Unmet Needs: A Critical Review.
Allergen immunotherapy (AIT) has been evaluated throughout several studies over the last years. A position paper from the European Academy of Allergy and Clinical Immunology highlighted the total combined symptoms score as the method to record the primary end point in AIT studies for allergic rhinitis, but this score still needs to be formally validated and more work done for other allergic diseases. These aspects still seem to be the main unmet need in the evaluation of AIT clinical outcomes in clinical trials.


Involvement of cutavirus in a subset of patients with cutaneous T-cell lymphoma with an unfavorable outcome.
European studies suggest an association between cutavirus (CuV) and cutaneous T-cell lymphoma (CTCL); however, the worldwide prevalence of CuV in patients with CTCL and its prognostic impact remain unknown. We investigated the prevalence and viral loads of CuV DNA using biopsy specimens from the lesional skins of 141 Japanese patients with cutaneous malignancies, including 55 patients with various types of CTCL. CuV DNA was detected significantly more frequently in biopsies from patients with mycosis fungoides (MF) (38% [13/34]; the most common subtype of CTCL) than in those from patients with other cutaneous malignancies (6% [6/107]; P<0.001). The viral-load range in patients with CuV DNA-positive MF was 23-3922 copies/103 cells and 8-65 copies/μg of DNA. A phylogenetic analysis using the partial sequences of the CuV viral capsid protein 1 (VP1)/VP2 genes revealed that the CuV sequences identified here were clustered in a Japanese-specific clade distinct from that comprising CuV sequences from European patients with MF. Kaplan-Meier curves and a log-rank test showed that CuV positivity was associated with a shorter disease-specific survival in patients with MF (P = 0.031), whereas no significant difference in overall survival was observed (P = 0.275). No significant correlation was observed between CuV DNA load and survival in patients with CuV-positive MF. Our results suggest that CuV is associated with MF in a subset of Japanese patients. Large-scale prospective studies are warranted to clarify the role of CuV status, especially regarding the viral genotype, on adverse outcomes in patients with CuV-positive MF.


[Diagnostic measures in bronchial asthma].
The diagnostic steps for in five groups divided forms of bronchial asthma are listed and are discussed. The diagnosis includes: 1. the anamnesis. 2. the clinical examination including X-ray, lung function tests, bronchologic inspection a.s.o., 3. special examinations for allergy including skin tests, provocation tests and pharmacodynamic tests, 4. serological-immunological methods of examination including determination of total IgE, specific IgE and several serum proteins.


Fundamental issues in mosquito surveillance for arboviral transmission.
Marked spatiotemporal variabilities in mosquito infection of arboviruses, exemplified by the transmission of West Nile virus (WNV) in America, require adaptive strategies for mosquito sampling, pool screening and data analyses. Currently there is a lack of reliable and consistent measures of risk exposure, which may compromise comparison of surveillance data. Based on quantitative reasoning, we critically examined fundamental issues regarding mosquito sampling design and estimation of transmission intensity. Two surveillance strategies were proposed, each with a distinct focus, i.e. targeted surveillance for detection of low rates of mosquito infection and extensive surveillance for evaluation of risk exposure with high levels of mosquito infection. We strongly recommend the use of indicators embodying both mosquito abundance and infection rates as measures of risk exposure. Aggregation of surveillance data over long periods of time and across broad areas obscures patterns of focal arboviral transmission. We believe that these quantitative issues, once addressed by mosquito surveillance programs, can improve the epidemiological intelligence of arbovirus transmission.


Acral hyperpigmented macules and longitudinal melanonychia in AIDS patients.
Two patients with AIDS are described who developed acral hyperpigmented macules of the fingers, palms and soles, buccal mucosa and genitalia, associated with longitudinal melanonychia. These pigmentary changes seemed to be independent of zidovudine and were associated in one with diffuse melanoderma and elevated levels of alpha-MSH. Histological and ultrastructural studies showed an increase of the dendrites and pigmentation of the melanocytes and few melanosomes in the keratinocytes.


Synthesis of high-complexity rhythmic signals for closed-loop electrical neuromodulation.
We propose an approach to synthesizing high-complexity rhythmic signals for closed-loop electrical neuromodulation using cognitive rhythm generator (CRG) networks, wherein the CRG is a hybrid oscillator comprised of (1) a bank of neuronal modes, (2) a ring device (clock), and (3) a static output nonlinearity (mapper). Networks of coupled CRGs have been previously implemented to simulate the electrical activity of biological neural networks, including in silico models of epilepsy, producing outputs of similar waveform and complexity to the biological system. This has enabled CRG network models to be used as platforms for testing seizure control strategies. Presently, we take the application one step further, envisioning therapeutic CRG networks as rhythmic signal generators creating neuromimetic signals for stimulation purposes, motivated by recent research indicating that stimulus complexity and waveform characteristics influence neuromodulation efficacy. To demonstrate this concept, an epileptiform CRG network generating spontaneous seizure-like events (SLEs) was coupled to a therapeutic CRG network, forming a closed-loop neuromodulation system. SLEs are associated with low-complexity dynamics and high phase coherence in the network. The tuned therapeutic network generated a high-complexity, multi-banded rhythmic stimulation signal with prominent theta and gamma-frequency power that suppressed SLEs and increased dynamic complexity in the epileptiform network, as measured by a relative increase in the maximum Lyapunov exponent and decrease in phase coherence. CRG-based neuromodulation outperformed both low and high-frequency periodic pulse stimulation, suggesting that neuromodulation using complex, biomimetic signals may provide an improvement over conventional electrical stimulation techniques for treating neurological disorders such as epilepsy.


Ultrastructural insights into tomato infections caused by three different pathotypes of Pepino mosaic virus and immunolocalization of viral coat proteins.
This paper presents studies on an ultrastructural analysis of plant tissue infected with different pathotypes of Pepino mosaic virus (PepMV) and the immunolocalization of viral coat proteins. Because the PepMV virus replicates with a high mutation rate and exhibits significant genetic diversity, therefore, isolates of PepMV display a wide range of symptoms on infected plants. In this work, tomato plants of the Beta Lux cultivar were inoculated mechanically with three pathotypes representing the Chilean 2 (CH2) genotype: mild (PepMV-P22), necrotic (PepMV-P19) and yellowing (PepMV-P5-IY). The presence of viral particles in all infected plants in the different compartments of various cell types (i.e. spongy and palisade mesophyll, sieve elements and xylem vessels) was revealed via ultrastructural analyses. For the first time, it was possible to demonstrate the presence of crystalline inclusions, composed of virus-like particles. In the later stage of PepMV infection (14 dpi) various pathotype-dependent changes in the structure of the individual organelles (i.e. mitochondria, chloroplasts) were found. The strongest immunogold labeling of the viral coat proteins was also observed in plants infected by necrotic isolates. A large number of viral coat proteins were marked in the plant conductive elements, both xylem and phloem.


Effects of diabetes on stress-induced analgesia in mice.
The present studies were designed to determine whether streptozotocin-induced (STZ-induced) diabetes in mice can attenuate the development of antinociception induced by exposure to both foot shock and forced swimming stress. Foot shock stress produced significant analgesia both in control and diabetic mice. However, the extent of foot shock stress-induced analgesia (FSSIA) in diabetic mice was significantly lower than that in control mice. Naloxone (2 mg/kg, i.p.) significantly attenuated FSSIA in control mice, but was without effect on FSSIA in diabetic mice. One-minute swimming stress had no significant effect on tail-pinch latency in control mice, whereas 3-min swimming stress produced significant analgesia in these mice. Diabetic mice exhibited robust swimming stress-induced analgesia (SSIA): one-min swimming stress produced significant analgesia in diabetic mice. These analgesic effects were blocked by naltrindole, a selective antagonist of delta-opioid receptors, but not by pretreatment with beta-funaltrexamine, an irreversible and selective antagonist of mu-opioid receptors. These results suggest that the deficiency in the functioning of mu-opioid receptors caused by diabetes results in significant activation of an endogenous analgesic system, which is mediated mainly by delta-opioid receptors.


Playing With Antidepressants: Perspectives From Indian Australians and Anglo-Australians Living With Depression.
Patient perspectives were explored on the meaning and experience of antidepressant use by applying Johan Huizinga's theory of play to interviews from Indian Australians and Anglo-Australians diagnosed with depression. Through the analysis, the centrality of Huizinga's "magic circle" emerged, that is, defining the boundaries within which one could safely play. Consumption of antidepressants involved learning, breaking, and modulating rules of the game of adherence, then forging a new "magic circle." In these games, there were playful elements including experimentation, improvisation, absorption, and experiential learning. This application of Huizinga's theory in relation to antidepressant use is a novel approach in the literature on medication non/adherence. This application not only opens a new theoretical line of inquiry but also shows that antidepressant non/adherence is not a static practice but dynamic and changing, revealing critical insights around participant's agency, capabilities, desires, and notions of selfhood with regard to managing their depression and conceptualizing their recovery.


Microelectrode Recording for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Advanced Parkinson's Disease: Advantage or Loss of Time?
To investigate the effect of using microelectrode recording (MER) on the length of time required to carry out a deep brain stimulation (DBS) procedure of the subthalamic nucleus in patients with Parkinson's disease (PD). The time required to include MER in the DBS operation was calculated for the first and second sides in 24 patients with PD. The number of microelectrodes used on each trajectory for the first and second sides, and the percentage of permanent electrodes implanted on each trajectory for the first and second sides, were quantified. The average times taken to use MER were 23.4 ± 6.2 minutes, 17.4 ± 6.5 minutes, and 41.2 ± 6.3 minutes for the first side, second side and total procedure, respectively. In 75% of patients, the permanent electrode was implanted at the planned target site for the first side, and in 61% of patients for the second side. MER extends the time required to carry out the DBS procedure. However, during surgery, it provides real-time information on the electrodes' neurophysiological locations and helps the surgical team choose an alternative target if the planned target does not produce satisfying results.


Transformative Innovations in Reproductive, Maternal, Newborn, and Child Health over the Next 20 Years.
As part of the "Grand Convergence: Aligning Technologies and Realities in Global Health" Collection, Cyril Engmann and colleagues discuss promising innovations that have the potential to move the RMNCH agenda forward.


Course of comorbid anxiety disorders among adults with bipolar disorder in the U.S. population.
To examine the prevalence and correlates of comorbid anxiety disorders among individuals with bipolar disorders (BP) and their association with prospectively ascertained comorbidities, treatment, and psychosocial functioning. As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for BP-I (n = 1172) and BP-II (n = 428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart. Sixty percent of individuals with BP had at least one lifetime comorbid anxiety disorder. Individuals with BP and anxiety disorders shared lifetime risk factors for major depressive disorder and had prospectively more depressive and manic/hypomanic episodes, suicidal ideation, suicide attempts, and more treatment seeking than those without anxiety. During the follow-up, higher incidence of panic disorder, drug use disorders, and lower psychosocial functioning were found in individuals with BP with versus without anxiety disorders. Anxiety disorders are prospectively associated with elevated BP severity and BP-related mental health service use. Early identification and treatment of anxiety disorders are warranted to improve the course and outcome of individuals with BP.


Peptide histidine methionine (PHM) and the human male genitalia.
Peptide histidine methionine-like immunoreactivity (PHM-IR) has been demonstrated to be present in the human penis both by radioimmunoassay and immunohistochemistry with particularly high levels in the corpus cavernosum and vas deferens. In the cavernosa, PHM-IR has been localised entirely, in nerves around arteries. High performance liquid chromatography indicated that this PHM-IR co-eluted with synthetic PHM but not porcine PHI. The presence of PHM-IR in the penis suggests that this neuropeptide may play a functional role in penile function.


Air-liquid interface culture of serially passaged human nasal epithelial cell monolayer for in vitro drug transport studies.
The objective of this study was to establish a drug transport study using human nasal epithelial (HNE) cell monolayers cultured by the air-liquid interface (ALI) method using serum-free medium (BEGM:DME/F12, 50:50). The cells were developed and characterized in comparison to those that have been previously cultured by the liquid-covered culture (LCC) method. The epithelial cell monolayer cultured by the ALI method resulted in a significantly higher transepithelial electrical resistance value (3,453 +/- 302 ohm x cm(2)) that was maintained (>1,000 ohm x cm(2)) for up to 20 days compared with that cultured by the LCC method. Observation by scanning electron microscopy revealed mature cilia after 2 weeks in the ALI culture, while flatten unhealthy ciliated cells were observed in the LCC method. After 21 days, higher level of MUC5AC and 8 mRNA were expressed in ALI culture which confirmed the secretory differentiation of HNE monolayers in vitro. No significant difference in the permeability coefficients of a model hydrophilic marker ((14)C-mannitol) and a lipophilic drug (budesonide) was observed between the two conditions on day 7. The passage 2-3 of the HNE monolayer using ALI condition retained the morphology and differentiated features of normal epithelium. Thus it would be a suitable model for in vitro nasal drug delivery studies.


Memory-enhancing treatments reverse the impairment of inhibitory avoidance retention in sepsis-surviving rats.
Survivors from sepsis have presented with long-term cognitive impairment, including alterations in memory, attention, concentration, and global loss of cognitive function. Thus, we evaluated the effects of memory enhancers in sepsis-surviving rats. The rats underwent cecal ligation and perforation (CLP) (sepsis group) with 'basic support' (saline at 50 mL/kg immediately and 12 hours after CLP plus ceftriaxone at 30 mg/kg and clindamycin at 25 mg/kg 6, 12, and 18 hours after CLP) or sham-operated (control group). After 10 or 30 days, rats were submitted to an inhibitory avoidance task. After task training, animals received injections of saline, epinephrine, naloxone, dexamethasone, or glucose. Twenty-four hours afterwards, animals were submitted to the inhibitory avoidance test. We demonstrated that memory enhancers reversed impairment in the sepsis group 10 and 30 days after sepsis induction. This effect was of lower magnitude when compared with sham animals 10 days, but not 30 days, after sepsis. Using different pharmacologic approaches, we conclude that the adrenergic memory formation pathways are responsive in sepsis-surviving animals.


Morphologic changes in the arterial bed of the penis with aging. Relationship to the pathogenesis of impotence.
The arterial vascular bed of the penis has been studied histologically in postmortem material from 30 males in the age range 19 to 85 years, mean 57. Fifteen of these propositi had had diabetes mellitus of average duration of 13 years. In all males more than 38 years old, there was fibrous substitution of the longitudinal smooth muscle in the Ebner pads. Later this was complemented by fibrous proliferation of the intima, medial fibrosis, calcification, and narrowing of the lumen to obilteration from thrombi. The extent of the pathology was apparently related to both age and diabetes mellitus. The nature and extent of the changes indicate that they must necessarily lead to a limitation of the basic function of this arterial tree, i.e., to increase essentially the flow of blood to the cavernous bodies at the time of the erection. These changes can play a decisive role in explaining impotence that occurs with aging, particularly in diabetics.


RhoA/ROCK-dependent pathway is required for TLR2-mediated IL-23 production in human synovial macrophages: suppression by cilostazol.
IL-23 is produced by antigen presenting cells and plays critical roles in immune response in rheumatoid arthritis. In this study, we investigated whether the RhoA/Rho-kinase pathway is required to elevate TLR2-mediated IL-23 production in synovial macrophages from patients with rheumatoid arthritis (RA), and then examined the suppressive effect of cilostazol on these pathways. IL-23 production was elevated by lipoteichoic acid (LTA), a TLR2 ligand, and this elevation was more prominent in RA macrophages than in those from peripheral blood of normal control. LTA increased the activation of RhoA in association with increased the nuclear translocation of NF-κB and its DNA-binding activity. Pretreatment of RA macrophages with the pharmacological inhibitors exoenzyme C3 (RhoA), Y27632 (Rho-kinase) or BAY11-7082 (NF-κB) inhibited IL-23 production by LTA. Inhibition of the RhoA/Rho-kinase pathway by these drugs attenuated NF-κB activation. Cilostazol suppressed the TLR2-mediated activation of RhoA, decreased NF-κB activity with down-regulated IL-23 production, and these effects were reversed by Rp-cAMPS, as an inhibitor of cAMP-dependent protein kinase. The expression of IL-23, which colocalized with CD68⁺ cells in knee joint of CIA mice, was significantly attenuated by cilostazol along with the decreased severity of arthritis. Taken together, the RhoA/Rho-kinase pathway signals TLR2-stimulated IL-23 production in synovial fluid macrophages via activation of NF-κB. Thus it is summarized that cilostazol suppresses TLR2-mediated IL-23 production by suppressing RhoA pathway via cAMP-dependent protein kinase activation.


Recommendations of Lifestyle Modification According to a Survey of First-Year University Students.
We analyzed what kind of lifestyle modification first-year university students need based on the results of a health-consciousness survey conducted in first-year students immediately after they entered a university. This population-based cross-sectional study used a "questionnaire survey on lifestyle and health for promoting health" conducted in Japan in 2015. From among an initial pool of 3,912 students, we excluded 314 due to insufficient data. The remaining 3,598 students (2,206 males and 1,392 females) were divided into four groups according to body mass index (BMI) based on Japan Society for the Study of Obesity "Guidelines for the management of obesity disease 2016": low (18.5 > BMI), less than standard (22.0 > BMI ≥ 18.5), standard or higher (25.0 > BMI ≥ 22.0) and obesity (BMI ≥ 25.0). Females had an ideal body image that was at a lower body weight regardless of their BMI. Males in the low BMI and obesity groups tended to be less aware of health issues. For each level of BMI, and in both males and females, the most frequent report of stress was "sometimes feel". The most frequent method for relieving stress was spending time with friends. Among males, those in the obesity group spent more time with "personal computers, televisions and games, etc." in a sitting position. When students were asked to rank which of their lifestyle habits needed the most improvement, "lack of exercise" was the highest, followed by "irregular schedule" and "dietary habits". In daily living behavior, a significant difference was observed for "exercise" among males, but not females. The attitudes of both males and females regarding the importance of physical activity and the necessity of efforts to improve health are presented. Health education for university students based on the attitudes may be useful for the prevention of lifestyle-related diseases for themselves in the future and before they become parents.


Efficacy of Empirical Radioiodine Therapy in Patients with Differentiated Thyroid Cancer and Elevated Serum Thyroglobulin without Evidence of Structural Disease: A Propensity Score Analysis.
We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3-285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan-Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis.


Leukemic cell lysis by activated human macrophages: significance of membrane-associated tumor necrosis factor.
In this study, we analyzed the mechanism(s) of leukemic cell lysis by human macrophages. Peripheral blood monocyte-derived macrophages were activated with recombinant interferon-gamma and lipopolysaccharide and their lytic activity against two leukemic cell lines (K562 and HL-60 cells) was assessed by an 111In releasing assay. Activated macrophages lysed these leukemic cells, and the lytic activity against leukemic cells was almost completely inhibited by anti-tumor necrosis factor (TNF) antibody. The macrophage-lysate prepared from activated macrophages also exhibited significant lytic activity against leukemic cells; this lytic activity was inhibited by anti-TNF antibody. The leukemic cells that we used for the cytotoxicity assays were resistant to recombinant TNF. The culture supernatant of activated macrophages did not show any lytic activity. These findings suggest that cell-associated TNF plays a role in macrophage-mediated cytotoxicity against leukemic cells.


Unilateral neglect is more severe and common in older patients with right hemispheric stroke.
Unilateral neglect after acute right hemispheric stroke significantly impedes poststroke recovery. We studied patients with right hemispheric stroke to determine whether increasing age was associated with more frequent or more severe neglect. Eight neglect tests within 5 days of symptom onset (and within 24 hours of admission) were administered to 204 subjects with acute right hemispheric stroke. Size of infarct was measured, and neglect tests were scored as percent error. "Any neglect" was defined by an elevated neglect test score, standardized relative to a group of normal controls. When tested for neglect soon after acute stroke admission, 69.6% of subjects older than 65 years had "any neglect" (defined by comparison to a group of normal controls), compared with 49.4% of subjects aged 65 years and younger (p = 0.008). For every additional 10 years of age, patients were 1.83 times as likely to have neglect, even after adjusting for diffusion-weighted imaging (DWI) infarct volume and NIH Stroke Scale (NIHSS) score (95% CI 1.38-2.43). In addition, DWI volume and NIHSS independently predicted neglect. Score on virtually all of the neglect tests worsened as an effect of age. Percentage error on a line cancellation task was 3.8% higher for every additional 10 years of age, after adjustment for DWI volume and NIHSS (p = 0.006). Similar results were found for other neglect tests. Increasing age in patients with acute right hemispheric stroke significantly increases the odds of unilateral neglect as well as severity of neglect, independently of size of the stroke or NIH Stroke Scale score. The reason for this finding in older patients may be because they have more brain atrophy and may be less able to compensate for cerebral infarction, or because they tend to have more cardioembolic strokes, which may be more cortically based.


Hypothetic association between greater sympathetic activity and prostate cancer.
Among men, prostate cancer is the most common cancer diagnosed, and the second leading cause of death from cancer in the industrialized countries. In spite of substantial progress in research, diagnosis and treatment, the causes of prostate cancer remain largely unknown. In this paper, we propose the hypothesis that prostate cancer represents another entity in the constellation of disease incited by the greater sympathetic activity that develops with age. However, the specific mechanisms of changes of increased prostatic cell proliferation and carcinogenesis caused by the autonomic nervous system have not yet been clarified. In regard to this matter, future studies should outline a more complete mechanism.


Substrate specificity of protein tyrosine phosphatase: differential behavior of SHP-1 and SHP-2 towards signal regulation protein SIRPalpha1.
The substrate specificity of catalytic domains and the activation of full length protein tyrosine phosphatases, SHP-1 and SHP-2 have been investigated using synthetic phosphotyrosyl peptides derived from SIPRalpha1. We found that the catalytic domains of SHP-1 and SHP-2 exhibit different substrate specificity towards a longer trideca-peptide pY(469+3) ((-7)RPEDTLTpYADLDM(+5)) and not to the shorter decapeptide pY(469) ((-5)EDTLTpYADLD(+4)), the former being the substrate of SHP-2 only. Furthermore, the activation of full-length SHP-1 and not the SHP-2 by the deca/trideca-peptides suggested SIRPalpha 1 to be possibly acting as both an upstream activator and a substrate for SHP-1, and merely as the downstream substrate for SHP-2 in signaling events.


Day time-restricted feeding shows differential synchronizing effects on age-related changes of serotonin metabolism in SCN and the pineal gland in male Wistar rats.
The circadian timing system is synchronized by the environmental photic and non-photic signals. Light is the major cue that entrains the master circadian oscillator located in suprachiasmatic nucleus (SCN). With aging condition ocular light impairs because of the age-related deficiencies in the eye as a result the clock becomes less sensitive to light. In such case non-photic cues may play a major role in synchronizing the clock. Earlier studies have linked altered meal timings to induce many physiological changes including serotonin in different brain regions such as hypothalamus, brain stem and striatum. Much is not known about the effect of timed food restriction as a non-photic stimulus on serotonergic system in SCN under aging condition. We report here the synchronizing effects of time-restricted feeding (TRF) as a non-photic stimulus on serotonin and its related metabolites in the SCN and pineal gland of male Wistar rats upon aging. Under food restriction daily rhythmicity of serotonin 5-HT and 5-HTOH was abolished whereas NAS, 5-MIAA and NAT showed a significant decrease in their daily pulses upon food restriction in 3 months (m) old rats. Under forced day time feeding schedule the mean 24 h levels of serotonin have significantly decreased in 12 and 24 m old animals in SCN and pineal gland. Most of the serotonin metabolites in the SCN and pineal gland of 12 and 24 m old ad libitum fed group rats have shown rhythmicity. 5-HT, NAS, MEL and NAT have shown daily rhythm in the SCN of 12 and 24 m old rats whereas 5-MIAA and 5-MTOH did not show daily rhythm in both the age groups. The mean 24 h levels of 5-HTP, 5-HIAA, 5-MIAA, 5-MTOH, MEL and NAT were increased in the pineal gland of 12 and 24 months old rats. This work help demonstrate the role of TRF in synchronising age induced desynchronization in serotonin metabolome.


Cumulative trauma disorder controls: the ergonomics program at Ethicon, Inc.
Over the past 10 years, Ethicon, Inc., has developed a successful program for the management of cumulative trauma disorders. The program is based on a multidisciplinary approach created through the existence of an ergonomics task force. Various functions of the task force and examples of its operations are described.


Unique activation mechanism of protein kinase CK2. The N-terminal segment is essential for constitutive activity of the catalytic subunit but not of the holoenzyme.
CK2 is an essential, ubiquitous, and highly pleiotropic protein kinase whose catalytic subunits (alpha and alpha') and holoenzyme (composed by two catalytic and two regulatory beta-subunits) are both constitutively active, a property that is suspected to contribute to its pathogenic potential. Extensive interactions between the N-terminal segment and the activation loop are suspected to underlie the high constitutive activity of the isolated catalytic subunit. Here we show that a number of point mutations (Tyr(26) --> Phe, Glu(180) --> Ala, Tyr(182) --> Phe) and deletions (Delta 2-6, Delta 2-12, Delta 2-18, Delta 2-24, Delta 2-30) expected to affect these interactions are more or less detrimental to catalytic activity of the alpha-subunit of human CK2, the deleted mutants Delta 2-24 and Delta 2-30 being nearly inactive under normal assay conditions. Kinetic analyses showed that impaired catalytic activity of mutants Delta 2-12, Delta 2-18, Delta 2-24, and Y182F is mainly accounted for by dramatic increases in the K(m) values for ATP, whereas a drop in K(cat) with K(m) values almost unchanged was found with mutants Y26F and E180A. Holoenzyme reconstitution restored the activity of mutants Delta 2-12, Delta 2-18, Y26F, E180A, and Y182F to wild type level and also conferred catalytic activity to the intrinsically inactive mutants, Delta 2-24 and Delta 2-30. These data demonstrate that specific interactions between the N-terminal segment and the activation loop are essential to provide a fully active conformation to the catalytic subunits of CK2; they also show that these interactions become dispensable upon formation of the holoenzyme, whose constitutive activity is conferred by the beta-subunit through a different mechanism.


[Analysis of the characteristics of door-to-door advertising sent by supermarkets in the Principality of Asturias (Spain): a cross-sectional study].
To analyze which foods and beverages, frequently included in advertising mail delivered by supermarkets in the Principality of Asturias, can be considered essential for consumption by the population, as well as to compare their price with that of essential products. Cross-sectional, descriptive study of supermarket sales circulars delivered to seven homes in Asturias (Spain) by four supermarket chains from July to December 2018. Type of product, its classification as essential or non-essential and mean price of the advertised product were registered. The study identified 14,314 products, mostly belonging to the categories: "cakes, pastries, chocolate, sugar, and sweeteners" (15.3?%), "milk and milk derivatives" (9.7?%), "processed meats".and "alcoholic beverages" (8.9?% each) and "ready-made" (8.4?%). Products considered to be non-essential were found to predominate (61.9?%). Significant differences in product type were observed between supermarket chains. Essential products had a lower mean price than the non-essential products, both overall and for each supermarket chain, and was significantly lower for one of them. . Products which are non-essential from the point of view of health, such as sugar-rich products, processed meats, and alcoholic beverages, dominated the advertising mail delivered door-to-door by supermarkets in the Principality of Asturias. On a positive note, the prices of essential products, such as fresh fruit and vegetables, were, on average, significantly lower than the prices of non-essential products.


Syphilis mimetic nanoparticles for cuproptosis-based synergistic cancer therapy via reprogramming copper metabolism.
Small cell lung cancer (SCLC) is one of the most devastating type of human lung cancer and has a high propensity to metastasize into the brain. Cuproptosis recently has been defined as a copper dependent cell death, offers a new lens to develop the novel copper-based nanostructure inducing cuproptosis for suppressing tumor growth and metastasis. Here, we report a syphilis mimetic TP0751-peptide decorated stem cell membrane-coated copper-based metal organic framework (Cu-MOF) nanodelivery system for SCLC brain metastasis. The Cu-MOF is employed as nanocarrier to support siRNA with high loading efficiency, and its pH sensitivity facilitates endosomal disruption upon cellular uptake. Furthermore, the cell membrane coating Cu-MOF presents a good biocompatibility, high BBB transcytosis, and specific uptake by tumor cells within the brain. In vitro and in vivo trials have shown that TP-M-Cu-MOF/siATP7a exhibited high silencing efficiency against target gene, specifically blocked copper trafficking, increased copper intake, triggered cuproptosis, and improved therapeutic efficacy in SCLC brain metastasis tumor-bearing mice. Overall, the biomimetic nanodelivery platform presented here further offers a promising way of orchestrating gene therapy to target copper-dependent signalling for reprogramming copper metabolism and cuproptosis-based synergistic therapy in mice bearing brain metastases.


Assessments of the effects of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) on human intestinal health from the aspects of intestinal flora changes and cytotoxicity to human cells.
Organophosphorus flame retardants (OPFRs) are now drawing the public's attention due to their potential toxicity. Given that contaminated food may result in the ingestion of OPFRs to the human intestine, further investigation is required to determine the potential adverse effects of these compounds on human intestinal health. The present study aimed to comprehensively assess the effect of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a typical OPFR, on human intestinal health by evaluating both intestinal flora and human cell Caco-2. Based on the results, TDCPP exposure altered the composition of intestinal flora and increased the proportion of pathogenic bacteria. PICRUSt2 analysis revealed that certain pathways were affected by TDCPP, and the resulting metabolic disorders might cause health problems. Orthologous genes of glutathione S-transferase and multidrug efflux system were up-regulated, demonstrating that the bacteria resisted TDCPP to maintain their vitality. Compared to the other two OPFRs, TDCPP induced greater cytotoxicity, and the results were consistent with the dose-effect relationship. Three OPFRs, especially TDCPP, caused the release of lactate dehydrogenase, accumulation of ROS, decline in mitochondrial membrane potential and increase in intracellular Ca2+, which could consequently induce cell death. The simultaneous effects of TDCPP on both intestinal cells and intestinal flora are likely to engender more severe intestinal health issues.


Endovascular repair of aortic arch false aneurysm with branched endograft.
This case report describes the use of a customized branched device for the treatment of a distal anastomotic false aneurysm in an ascending to descending interposition graft in a 34-year-old Jehovah's Witness with congenital aortic arch interruption. A single branched customized stent graft device was used to successfully exclude the false aneurysm. The procedure was challenging due to the abnormal congenital anatomy. The planning, operative technique, and successful execution are described in this case report.


4-hydroxy-2-nonylquinoline: a novel iron chelator isolated from a bacterial cell membrane.
The membrane associated iron chelator of Pseudomonas aeruginosa has been extracted from membranes of iron-rich cells with ethanol and purified by reverse phase HPLC. Using 13C NMR and FAB mass spectroscopy, the structure of the chelator has been determined to be 4-hydroxy-2-nonylquinoline. This compound has been previously isolated and named pseudan IX, a name which we use here. We synthesized pseudan IX and show that the spectral properties of the synthesized compound and the purified compound are nearly identical. Also purified from the ethanol extract of membranes is 4-hydroxy-2-heptylquinoline, i.e., pseudan VII. Bacterially purified pseudan IX binds iron as indicated by the incorporation of radiolabeled iron into the chelator and by the formation of pink micelles in a concentrated ethanol extract. The formation of pink micelles upon addition of iron to the synthesized compound indicates that it binds iron.


A reliable method with good cell preservation for the demonstration of peroxidase activity in human platelets and megakaryocytes.
We have tried to improve existing methods for demonstration of platelet peroxidase (PPO) in human platelets and megakaryocytes by introducing a fixation of 0.1% glutaraldehyde prior to incubation in the DAB medium. This prefixation with low concentration of glutaraldehyde preserves excellent morphological detail and does not inhibit PPO activity. All 23 platelet-rich plasma samples show PPO reaction product in the dense tubular system after incubation in DAB medium with 0.003% H2O2. When 0.01% H2O2 is used in excessive DAB medium, PPO activity can also be demonstrated in platelets and megakaryocytes of bone-marrow cell suspensions. This method can be used for the identification of megakaryoblasts in acute non-lymphocytic leukemia, myelodysplastic syndromes and in blastic crisis of chronic myeloid leukemia. PPO cytochemistry can be combined with postfixation in a OsO4-ruthenium red mixture. This method reveals alpha-granules, dense bodies, microtubuli, glycogen, mitochondria, dense tubular system and invaginated membrane system in the same platelet and is useful for investigation of platelet ultrastructure.


Measuring range of active cervical rotation in a position of full head flexion using the 3D Fastrak measurement system: an intra-tester reliability study.
Most external assessments of cervical range of motion assess the upper and lower cervical regions simultaneously. This study investigated the within and between days reliability of the clinical method used to bias this movement to the upper cervical region, namely measuring rotation of the head and neck in a position of full cervical flexion. Measurements were made using the Fastrak measurement system and were conducted by one operator. Results indicated high levels of within and between days repeatability (range of ICC2,1 values: 0.85-0.95). The ranges of axial rotation to right and left, measured with the neck positioned in full flexion, were approximately 56% and 50%, respectively of total cervical rotation, which relates well to the proportional division of rotation in the upper and lower cervical regions. These results suggest that this method of measuring rotation would be appropriate for use in subject studies where movement dysfunction is present in the upper cervical region, such as those with cervicogenic headache.