Histopathology of experimental Schistosoma bovis infection in goats.
The inflammatory host response to Schistosoma bovis in young goats was studied at necropsy by light microscopy 34 weeks after primary exposure to 3,000 cercariae (group B, n = 6), 34 weeks after primary exposure to 3,000 cercariae followed by challenge with 2,500 cercariae at week 17 (group C, n = 5), and 17 weeks after primary exposure to 2,500 cercariae, given on week 17 of the experiment (group D, n = 6). Three goats served as uninfected controls. The faecal egg output had been minimal for 17 weeks prior to necropsy in groups B and C and only for the last 2 weeks in group D. Histological studies were carried out on the small intestine, liver, lung and spleen, and tissue egg counts were performed. In sections of the small intestine and liver, a panel of histopathological variables were quantitated to characterize the host response and differences between groups of animals were evaluated with one way analysis of variance. The mean tissue egg count in the small intestine was slightly but not significantly higher in group C than group B and about twice as high in group D (D vs B or C p < 0.01). Group means of numbers of inflammatory foci per section of gut wall corresponded well with those of tissue egg counts, suggesting that the rate of inflammatory destruction of eggs did not differ markedly between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Anogenital distance in newborn infants conceived by assisted reproduction and natural conception.
Does anogenital distance (AGD) differ in newborn infants conceived through assisted reproduction technology (ART) compared with those conceived naturally? This case-control study looked at anthropometric and anogenital measurements in 247 male and 200 female newborns born after ART (n = 121) or natural conception (n = 326), within 24 h of birth. Anogenital measurements included distance from the centre of the anus to the anterior clitoris (AGDAC) and to the posterior fourchette (AGDAF) in female infants, and from the centre of the anus to the posterior base of the scrotum (AGDAS) and to the anterior base of the penis (AGDAP) in male infants. ART mothers were older, more likely to be nulliparous and delivered by Caesarean section at an earlier gestational week. AGDAS of male infants was approximately twice the AGDAF of female infants (17.6 ± 5.0 versus 9.1 ± 3.6 mm). AGDAF in female infants conceived by ART compared with those conceived naturally was not significantly different (8.8 ± 3.6 versus 9.3 ± 3.6 mm; P = 0.404). AGDAC were also comparable for both groups (27.4 ± 6.3 versus 27.7 ± 7.1 mm; P = 0.770). In male infants, no significant difference was seen between ART and natural conception groups in terms of AGDAS (17.4 ± 4.6 versus 17.7 ± 5.2 mm, P = 0.742) and AGDAP (37.5 ± 6.6 versus 38.0 ± 6.7 mm, P = 0.589). When adjusted for gestational age, weight, length and head circumference, mode of conception was not associated with differences in any of the anogenital measurements. AGD measurements in infants conceived by ART are no different from those of infants conceived naturally.


Early development of electrophysiological activity: Contribution of periodic and aperiodic components of the EEG signal.
Brain function rapidly changes in the first 2 years of life. In the last decades, resting-state EEG has been widely used to explore those changes. Previous studies have focused on the relative power of the signal in established frequency bands (i.e., theta, alpha, and beta). However, EEG power is a mixture of a 1/f-like background power (aperiodic) in combination with narrow peaks that appear over that curve (periodic activity, e.g., alpha peak). Therefore, it is possible that relative power captures both, aperiodic and periodic brain activity, contributing to changes in electrophysiological activity observed in infancy. For this reason, we explored the early developmental trajectory of the relative power in theta, alpha, and beta frequency bands from infancy to toddlerhood and compared it with changes in periodic activity in a longitudinal study with three waves at age 6, 9, and 16 to 18 months. Finally, we tested the contribution of periodic activity and aperiodic components of the EEG to age changes in relative power. We found that relative power and periodic activity trajectories differed in this period in all the frequency bands but alpha. Furthermore, aperiodic EEG activity flattened between 6 and 18 months. More importantly, only alpha relative power was exclusively related to periodic activity, whereas aperiodic components of the signal significantly contributed to the relative power of activity in theta and beta bands. Thus, relative power in these frequencies is influenced by developmental changes of the aperiodic activity, which should be considered for future studies.


[Ontogenetic features of autonomic homeostasis in children according to the data of variation pulsometry].
A method of variation pulsometry was used to determine the vegetative homeostasis state in 20 children aged from 4 to 14. Normotonic type of the cardiac rhythm regulation was observed in a group of children aged 4-5. In children aged 12-14 the effect of sympathetic area of the vegetative nervous system decreased while the effect of the parasympathetic one increased. The tension index, effect of the humoral regulation channel and the degree of cardiac rhythm control centralization decreased.


Nitrogen release and its influence on anammox bacteria during the decay of Potamogeton crispus with different values of initial debris biomass.
Aquatic macrophytes play a significant role in the nutrient cycle of freshwater ecosystems. However, nutrients from plant debris release into both sediments and overlying water if not timely harvested. To date, minimal information is available regarding nutrient release and its subsequent influences on bacterial communities with decaying debris. In this study, Potamogeton crispus was used as a model plant. Debris biomass levels of 0 g (control, J-CK), 10 g dry weight (DW) (100 g DW/m2, J-10 g), 40 g DW (400 g DW/m2, J-40 g) and 80 g DW (800 g DW/m2, J-80 g) were used to simulate the different biomass densities of P. crispus in field. The physicochemical parameters of overlying water and sediment samples were analysed. The community composition of anammox bacteria in the sediment was also analysed using 16S rRNA genes as markers. The results showed that dissolved oxygen and pH dramatically decreased, whereas total nitrogen (TN) and NH4+-N concentrations increased in the overlying water in the initial stage of P. crispus decomposition. However, NO3--N concentration changes in the overlying water were more complicated. The concentrations of organic matter, TN and NH4+-N in the sediment all increased, but the rate of increase varied among the groups with different initial biomass levels, indicating that these physicochemical properties in sediment are significantly affected by debris biomass level and decay time. In addition, the order of anammox bacteria abundance was J-40 g > J-CK > J-80 g > J-10 g. Moreover, the community structure of anammox bacteria were simpler compared to that of J-CK as debris biomass level increased. The results demonstrate that P. crispus debris decomposition could affect the ecological distribution of anammox bacteria. Such influence clearly varies with varying amounts of P. crispus biomass debris. This information could be useful for the management of aquatic macrophytes in freshwater ecosystems.


Validation of Algorithms to Identify Acute Myocardial Infarction, Stroke, and Cardiovascular Death in German Health Insurance Data.
Validation of outcomes allows measurement of and correction for potential misclassification and targeted adjustment of algorithms for case definition. The purpose of our study was to validate algorithms for identifying cases of acute myocardial infarction (AMI), stroke, and cardiovascular (CV) death using patient profiles, ie, chronological tabular summaries of relevant available information on a patient, extracted from pseudonymized German claims data. Based on the German Pharmacoepidemiological Research Database (GePaRD), 250 cases were randomly selected (50% males) for each outcome between 2016 and 2017 based on the inclusion criteria age ≥50 years and continuous insurance ≥1 year and applying the following algorithms: hospitalization with a main diagnosis of AMI (ICD-10-GM codes I21.- and I22.-) or stroke (I63, I61, I64) or death with a hospitalization in the 60 days before with a main diagnosis of CV disease. Patient profiles were built including (i) age and sex, (ii) hospitalizations incl. diagnoses, procedures, discharge reasons, (iii) outpatient diagnoses incl. diagnostic certainty, physician specialty, (iv) outpatient encounters, and (v) outpatient dispensings. Using adjudication criteria based on clinical guidelines and risk factors, two trained physicians independently classified cases as "certain", "probable", "unlikely" or "not assessable". Positive predictive values (PPVs) were calculated as percentage of confirmed cases among all assessable cases. For AMI, the overall PPV was 97.6% [95% confidence interval 94.8-99.1]. The PPV for any stroke was 94.8% [91.3-97.2] and higher for ischemic (98.3% [95.0-99.6]) than for hemorrhagic stroke (86.5% [76.5-93.3]). The PPV for CV death was 79.9% [74.4-84.4]. It increased to 91.7% [87.2-95.0] after excluding 32 cases with data insufficient for a decision. Algorithms based on hospital diagnoses can identify AMI, stroke, and CV death from German claims data with high PPV. This was the first study to show that German claims data contain information suitable for outcome validation.


Short-term changes in topometric indices after discontinuation of rigid gas permeable lens wear in keratoconic eyes.
To estimate the time taken for topometric indices to stabilize in keratoconic corneas following cessation of habitual RGP contact lens wear. A total of 29 eyes of 20 patients, diagnosed with mild to severe keratoconus were included in this prospective observational study. All patients were experienced RGP contact lens wearers (either conventional RGP or Rose K2 lens) with each patient having used these lenses for at least a year. Corneal topography was performed immediately following discontinuation of habitual contact lens wear at baseline and each of four consecutive visits, 1-week apart. An overall reduction in the keratometry and thickness values were noted on tomography immediately following cessation of contact lens wear and these indices increased significantly in the 1st week (P < 0.001). Consecutive visits following the first visit did not show any significant change in the topometric parameters (P > 0.05). Subgroup analysis revealed a similar trend in eyes with "severe" keratoconus and in eyes fitted with the "three-point touch" philosophy. However, eyes with "mild-moderate" keratoconus and those fitted with "apical clearance" fitting philosophy showed marginal differences even within the 1-week period of lens cessation. Maximum changes in keratometry and pachymetry values following discontinuation of RGP lens wear stabilize within the 1st week of cessation of rigid lens wear in a keratoconic cornea. These changes were more pronounced in patients with severe keratoconus and those with an apical bearing fit. This information would be useful for practitioners to assess the progression of keratoconus in RGP lens users before collagen cross-linking.


Digital imaging of stem cells by electron microscopy.
This chapter deals with basic techniques of scanning and transmission electron microscopy applicable to stem cell imaging. It is sometimes desirable to characterize the fine structure of embryonic and adult stem cells to supplement the images obtained by phase-contrast and confocal immunofluorescent microscopy to compare with the microstructure of cells and tissues reported in the literature. This would help confirm their true identity whilst defining their surface and internal morphology. The intention is to put a face on stem cells during their differentiation.


Environmental performance of plastic food packaging: Life cycle assessment extended with costs on marine ecosystem services.
Packaging can play a substantial role in moving towards more sustainable food systems by affecting the amount of food loss and waste. However, the use of plastic packaging gives rise to environmental concerns, such as high energy and fossil resource use, and waste management issues such as marine litter. Alternative biobased biodegradable materials, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) could address some of these issues. For a careful comparison in terms of environmental sustainability between fossil-based, non-biodegradable and alternative plastic food packaging, not only production but also food preservation and end-of-life (EoL) fate must be considered. Life cycle assessment (LCA) can be used to evaluate the environmental performance, but the environmental burden of plastics released into the natural environment is not yet embedded in classical LCA. Therefore, a new indicator is being developed that accounts for the effect of plastic litter on marine ecosystems, one of the main burdens of plastic's EoL fate: lifetime costs on marine ecosystem services. This indicator enables a quantitative assessment and thus addresses a major criticism of plastic packaging LCA. The comprehensive analysis is performed on the case of falafel packaged in PHBV and conventional polypropylene (PP) packaging. Considering the impact per kilogram of packaged falafel consumed, food ingredients make the largest contribution. The LCA results indicate a clear preference for the use of PP trays, both in terms of (1) impact of packaging production and dedicated EoL treatment and (2) packaging-related impacts. This is mainly due to the higher mass and volume of the alternative tray. Nevertheless, since PHBV has limited persistence in the environment compared to PP packaging, the lifetime costs for marine ES are about seven times lower, and this despite its higher mass. Although further refinements are needed, the additional indicator allows for a more balanced evaluation of plastic packaging.


New myotropic and metabotropic actions of pyrokinins in tenebrionid beetles.
Pyrokinins are a large family of insect neuropeptides exhibiting pleiotropic activity, but are predominantly myostimulatory hormones. In this study, four pyrokinins Tenmo-PK-1 (HVVNFTPRLa), Tenmo-PK-2 (SPPFAPRLa), Tenmo-PK-3 (HLSPFSPRLa) and Zopat-PK-1 (LPHYPRLa) from the neuro-endocrine system of two tenebrionid beetles, Tenebrio molitor and Zophobas atratus, were tested in homologous bioassays to evaluate their putative myotropic and glycaemic actions. The four investigated bioassays systems (the heart, oviduct, ejaculatory duct and hindgut) revealed species-specific and organ-specific myotropic actions for the pyrokinins tested. In most bioassays with both beetles, the peptides showed myostimulatory properties with different efficacy. However, the T. molitor heart is not sensitive to Tenmo-PK-1, Tenmo-PK-2 and Tenmo-PK-3, and one of the peptides Tenmo-PK-1, is myoinhibitory on the oviduct. Tenmo-PK-2, which is also present in Z. atratus, exerted an inhibitory effect on the contractions of the heart and ejaculatory duct muscles in this beetle. Such myoinhibitory properties of pyrokinins in insects are shown here for the first time. Only one of the peptides tested, Tenmo-PK-2, stimulated a hyperglycaemic response in the haemolymph of larvae of T. molitor and Z. atratus, and this effect suggests a possible additional metabotropic function of this peptide in beetles. The differences in the myotropic and glycaemic responses to pyrokinins suggest that these peptides modulate contractions of muscles from visceral organs and free sugar levels in the haemolymph of the beetles, through complex and species-specific mechanisms.


Policy shock effect of SDP on environmental total factors productivity: 53 coal cities versus 165 non-resource-based cities.
The trend of economic decline for coal cities is a serious threat to the high-quality development of China's economy, and how to improve the environmental total factor productivity (ETFP) has become an urgent issue. Based on the framework of data envelopment analysis (DEA), this paper estimates ETFP using the global Malmquist-Luenberger productivity index (GMLPI). We decompose GMLPI into environmental technical efficiency change (ETEC) and the best practice gap change (BPGC). Then, the difference-in-difference (DID) model combining propensity score matching (PSM) method is used to investigate the effect of the Sustainable Development Plan of National Resource-based Cities (2013-2020) (SDP) aiming to improve ETFP. The results indicate that (1) On average, the GMLPI and BPGC are rising, while the ETEC is decreasing in the observed sample period; the western regions have the biggest BPGC, while the eastern regions have the biggest ETEC; (2) The SDP significantly improves the GMLPI and BPGC but has little effect on the ETEC; Coal cities located in eastern and central regions have policy effect, while the western regions do not have. (3) The SDP affects ETFP through slowing down the economic growth rate and reducing population agglomeration, but promoting the optimization of industrial structure. Those findings have policy implications for improving ETFP and promoting the industrial upgrade of coal cities.


Increased numbers of circulating haematopoietic progenitor cells after treatment with high-dose interleukin-2 in cancer patients.
Immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been applied to patients with metastatic cancers for its antitumour activity. In the present study we investigated the effects of in vivo administration of IL-2 (3 x 10(6) U/m2/d, continuously i.v.) on haematopoiesis. Six patients with disseminated renal cell carcinoma, treated with IL-2 and LAK cells, were monitored for the numbers of white blood cells and circulating haematopoietic progenitor cells (HPC). During IL-2 treatment lymphopenia developed, followed by lymphocytosis after discontinuation of IL-2 infusions. IL-2 administration also resulted in neutrophilia and eosinophilia. Absolute numbers of circulating HPC declined markedly during IL-2 treatment. However, after completing IL-2 infusions, the numbers of circulating erythroid (BFU-E), myeloid (CFU-GM) and multipotential progenitor cells (CFU-GEMM) strongly increased, reaching a maximum after 5 d (day 10 from the start of IL-2 treatment). This increase did not result from repeated leucaphereses, since patients treated with IL-2 alone showed a similar response. In comparison with pretreatment levels the pool of circulating HPC expanded about 20-fold. This study illustrates that IL-2 treatment has a biphasic effect on the frequency of circulating BFU-E, CFU-GM and CFU-GEMM, causing a decrease during IL-2 infusion, followed by an increase after IL-2 administration. The total number of progenitor cells harvested by four consecutive leucaphereses is in the range that is commonly used for peripheral blood stem cell autografting.


Leaching of depleted uranium in soil as determined by column experiments.
The basic features of the leachability of depleted uranium (DU) projectiles in soil was investigated by using 12 projectiles (145-294 g DU) and 16 columns installed in an air-conditioned laboratory. Two soils widely distributed in Europe, a sandy-loamy cambisol and a silty-loamy luvisol, were filled into the columns (3.3 kg dry soil each). The effluents of all columns were collected weekly during the observation period of 1 year. In 648 samples, 235U and 238U were determined by inductively coupled plasma mass spectrometry. The leaching rates of 238U from natural uranium were in general about 0.01 microg week-1 or smaller, while those of 238U from the DU munitions varied considerably and reached values of up to 100 microg week-1, for the different columns. In total, about 0.3 microg natural uranium corresponding to 20 ppm of its inventory in the soil was leached during the observation period. From the projectiles, an average of about 50 microg DU were leached corresponding to 18 ppm of the corroded DU mass (about 1.6% of the mean initial DU mass of the projectiles). Assuming that corrosion and leaching continue as observed, the mobilisation of 238U from DU munitions will last, on an average, for thousands of years in the soils investigated, while the munitions themselves will have been corroded after a much shorter time. It is proposed to use, for the investigated soil types, the mean leaching rates of the six columns with projectiles for transport calculations of 238U to the groundwater and, thus, for a better risk assessment of the water-dependent uptake pathways of DU.


The impact of fluid mechanical stress on Corynebacterium glutamicum during continuous cultivation in an agitated bioreactor.
The effect of mechanical stresses generated by an extreme agitation intensity or a high aeration rate on growth parameters and cell physiology were studied during continuous cultivation of the Gram-positive bacterium Corynebacterium glutamicum. It is concluded that variations in agitation, aeration rate, or dO2 concentrations down to about 1% of saturation do not damage the bacterial cells or cause a significant change in physiological response, as measured by flow cytometry, even though the cell size was slightly reduced.


The effects of a cost-education program on hospital charges.
An educational intervention designed to change physicians' use of inpatient services was implemented on two general medical services for a year. The intervention consisted of a brief orientation to cost containment issues, a pamphlet that outlined practical cost containment strategies and listed the charges for commonly ordered tests and services, and access to detailed interim patients' bills generated during the hospitalization. Two concurrent control services received no intervention. Over 1,600 admissions were evaluated. The geometric mean length of stay was 0.61 days shorter on intervention services compared with control (5.15 vs. 5.76 days, p less than 0.01). The geometric mean hospital charges were $388 less for intervention patients ($3,199 vs. $3,587, p less than 0.005). Neither patients' demographic characteristics nor case mix could explain the reductions. The authors conclude that a simple program utilizing information already in existence in most hospitals can result in a significant and meaningful reduction in length of stay and charges.


Congenital aortico-left ventricular tunnel in fetuses and infants.
Congenital aortico-left ventricular tunnel (ALVT) is a rare congenital heart disease. A 27-year-old woman was referred to us at 37 weeks gestation with fetal cardiac enlargement. The left ventricle (LV) of the fetus was enlarged. Fetal aortic valve (AoV) ring diameter spread was observed. Back flow from the AoV margins to the LV was observed. The prenatal diagnosis of the fetus was aortic regurgitation (AR). A male neonate was delivered by cesarean section at 40 weeks gestation. We made the diagnosis of ALVT because the aorta and the LV of the neonate showed a tunnel with blood flow on echocardiography. We took another look at the fetal echocardiography. The neonate underwent surgery for exacerbation of heart failure on the 7th day after birth. Trivial flow from the tunnel and mild AR were observed after surgery.


A personal perspective from the UK: ageing and psychiatrists.
Psychiatrists appointed to National Health Service (NHS) consultant posts in the United Kingdom before a specific date in 1995 qualified for early retirement and this has implications for workforce planning. The author reflects on the implications this has for ageing psychiatrists and for relationships between psychiatrists and patients and families using mental health services, from the perspective of a psychiatrist who took advantage of the opportunity to retire early from a consultant post in the NHS and to develop a new career. Older psychiatrists continuing to practise after retirement from consultant roles may bring disadvantages and advantages. Older psychiatrists may be a valuable resource for future mental health services, and they may be in a position to try out new ways of working which might be relevant to their younger colleagues in the uncertain future faced by mental health services at a time of austerity.


Chemotactic factor inactivator release from rat leukocytes.
Rat neutrophils, alveolar macrophages, and peritoneal macrophages each released chemotactic factor inactivator (CFI) activities under conditions of endocytosis (uptake of opsonized zymosan particles and preformed immune complexes). CFI activities in supernatant fluids from phagocytizing leukocytes were found for the chemotactic factors from the third (C3) and the fifth (C5) components of complement and for the bacterial chemotactic factor (present in culture supernatant fluids from Escherichia coli.) CFI activity could also be demonstrated in homogenates obtained from disrupted leukocytes. CFI release from intact leukocytes was dependent on the duration of incubation of leukocytes with the phagocytic stimulus. No quantitative relationships were noted between the amount of CFI activity and the amount of beta-glucuronidase in phagocytic supernatant fluids released from leukocytes. The release of CFI activities from phagocytizing leukocytes may represent a regulatory ("turn-off") mechanism for the inflammatory response.


The relationship between challenging parenting behaviour and childhood anxiety disorders.
This research investigates the relationship between challenging parenting behaviour and childhood anxiety disorders proposed by Bögels and Phares (2008). Challenging parenting behaviour involves the playful encouragement of children to go beyond their own limits, and may decrease children's risk for anxiety (Bögels and Phares, 2008). Parents (n=164 mothers and 144 fathers) of 164 children aged between 3.4 and 4.8 years participated in the current study. A multi-method, multi-informant assessment of anxiety was used, incorporating data from diagnostic interviews as well as questionnaire measures. Parents completed self-report measures of their parenting behaviour (n=147 mothers and 138 fathers) and anxiety (n=154 mothers and 143 fathers). Mothers reported on their child's anxiety via questionnaire as well as diagnostic interview (n=156 and 164 respectively). Of these children, 74 met criteria for an anxiety disorder and 90 did not. Fathers engaged in challenging parenting behaviour more often than mothers. Both mothers' and fathers' challenging parenting behaviour was associated with lower report of child anxiety symptoms. However, only mothers' challenging parenting behaviour was found to predict child clinical anxiety diagnosis. Shared method variance from mothers confined the interpretation of these results. Moreover, due to study design, it is not possible to delineate cause and effect. The finding with respect to maternal challenging parenting behaviour was not anticipated, prompting replication of these results. Future research should investigate the role of challenging parenting behaviour by both caregivers as this may have implications for parenting interventions for anxious children.


Seroprevalence of six reproductive pathogens in European wild boar (Sus scrofa) from Spain: the effect on wild boar female reproductive performance.
We studied the seroprevalence of six reproductive pathogens in Spanish hunter-harvested wild boar females. The sample was representative of the hunting harvest in the studied hunting estates. Mean antibody prevalences were: 60.6+/-0.06% for Aujeszky's disease virus (ADV), 56.6+/-0.09% for porcine parvovirus (PPV), 51.8+/-0.06% for porcine circovirus type 2 (PCV2), 29.7+/-0.09% for Brucella spp. and 36.3+/-0.1% for Toxoplasma gondii. We did not detect antibodies against porcine reproductive and respiratory syndrome virus (PRRSv). ADV seroprevalence was associated with PPV and PCV2 seroprevalence in Spanish wild boar females. Ovulation rate in the studied wild boar females was 4.41+/-0.16 (n=120), mean litter size was 3.91+/-0.16 (n=82) and the partial resorption index 0.92+/-0.17 (n=66). Ovulation rate and litter size were statistically associated with age. T. gondii seroprevalence was negatively related to ovulation rate and partial resorption index. Wild boars from managed fenced estates had antibodies against more pathogens than wild boars from open estates. Potential relations between management of wild boar populations and exposure of individuals to different reproductive pathogens are discussed.


Modulation of resource allocation by intelligent individuals in linguistic, mathematical and visuo-spatial tasks.
This study investigates two questions: first, how individuals with high-intelligence allocate cognitive resources while solving linguistic, mathematical and visuo-spatial tasks with varying degree of difficulty as compared to individuals with low intelligence? Second, how to distinguish between high and low intelligent individuals by analyzing pupil dilation and eye blink together? We measured the response time, error rates along with pupil dilation and eye blink rate that indicate resource allocation. We divided the whole processing into three stages namely: pre-stimuli (5s prior to stimuli onset), during stimuli and post stimuli (until 5s after the response) for better assessment of preparation and resource allocation strategies. Individuals with high intelligence showed greater task evoked pupil dilation, decreased eye blink with less response time and error rates during-stimuli stage (processing) of tough linguistic and visuo-spatial tasks but not during mathematical tasks. The finding suggests that individuals with high intelligence allocate more resources if the task demands are high else they allocate less resources. Greater pre-stimuli pupil dilation and increased eye blink of high intelligent individuals in all tasks indicated their attentiveness and preparedness. The result of our study shows that individuals with high intelligence are more attentive and flexible in terms of altering the resource allocation strategy according to task demand. Eye-blinks along with pupil dilation and other behavioral parameters can be reliably used to assess the intelligence of an individual and the analysis of pupil dilation and blink rate at pre-stimuli stage can be crucial in distinguishing individuals with varying intelligence.


The weak rupiah: catching the tailwinds and avoiding the shoals.
The Indonesian rupiah depreciated 50% between July 2011 and February 2020. Blanchard et al. (Are capital inflows expansionary or contractionary? Theory, policy implications, and some evidence. NBER Working Papers 21619, National Bureau of Economic Research, Cambridge, MA, 2015) showed that capital outflows from emerging markets can reduce output by increasing the cost of financial intermediation and can increase output by increasing net exports. Regression results indicate that Indonesian banks are exposed to depreciations, but that exports are not stimulated by depreciations. The findings also indicate that Indonesia's export price index is positively correlated with commodity prices and negatively correlated with manufactured goods prices. Exporting more manufactures would reduce Indonesia's exposure to volatile commodity prices and allow depreciations to stimulate exports. This paper considers several steps that Indonesia could take to increase its manufacturing exports.


Presence of Contracaecum spp. in teleosts cultured and fished in Sardinia.
This study reports the results of the finding of Contracaecum spp. during a survey on endoparasites isolated from cultured and wild fish and also from some cephalopods caught in Sardinian waters. Contracaecum spp. is a nematode belonging to the Anisakidae, and is reported to cause zoonosis in humans. Nematodes were detected after visual inspection and enzymatic digestion and then identified by morphologic observation, which was confirmed by PCR. The results show that Contracaecum spp. were found in both fish caught from sea or lagoon, and in both cultured and wild fish: 33 of the parasitized samples were wild fish (24 caught in the sea and 9 in lagoons) and 11 were cultured ones. The prevalence of Contracaecum spp. was higher in Diplodus spp. (16.0%), Sparus aurata (15.8%) and Mullus spp. (14.6%). Larvae were also found by enzymatic digestion at muscular level in 5 species, with the highest prevalence in S. aurata (10.5%). The results of this study indicate that Contracaecum spp. was present in cultured fish such as S. aurata, Diplodus spp. and Dicentrarchus labrax. All cultured fish with parasites were collected from land-based semi-intensive tanks whose water came from an adjacent lagoon. Finally, the evidence that this parasite is found in both cultured and wild fish leads us to re-consider the zoonotic potential of Contracaecum spp., in particular when one bears in mind its dimensions at the L3 stage, when it is barely visible to the human eye.


Composition, distribution, health risks, and drivers of phthalates in typical red paddy soils.
The accelerated accumulation of phthalate esters (PAEs) in paddy soils poses a serious threat to human health. However, related studies mainly focus on facility vegetable fields, drylands, and orchards, and little is known about paddy soils. In this study, 125 samples were collected from typical red paddy fields to investigate the pollution characteristics, sources, health risks, and main drivers of PAEs. Soil physicochemical properties, enzyme activity, and bacterial community composition were also measured simultaneously. The results showed that eight PAE congeners were detected ranging from 0.17 to 1.97 mg kg-1. Di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and di-isobutyl phthalate (DIBP) were the most abundant PAE congeners, accounting for 81% of the total PAEs. DEHP exhibited a potential carcinogenic risk to humans through the intake route. The main PAEs were positively correlated with soil organic matter (SOM) and soil water content (SWC) contents. Low levels of PAEs increased bacterial abundance. Furthermore, most PAE congeners were positively correlated with hydrolase activity. Soil acidity and nutrient dynamics played a dominant role in the bacterial community composition, with PAE congeners playing a secondary role. These findings suggest that there may be a threshold response between PAEs and organic matter and nutrient transformation in red paddy soils, and that microbial community should be the key driver. Overall, this study deepens the understanding of ecological risks and microbial mechanisms of PAEs in red paddy soils.


FokI method of gene synthesis.
An accurate, fast and simple method is presented for synthesis of a gene, or any DNA fragment with a defined sequence. The method is based on the observation that large (approx. 100 bp long) inserts can be cloned into a plasmid using a technique of oligodeoxynucleotide (oligo)-directed double-strand (ds) break repair. The procedure involves transformation of Escherichia coli with a denatured mixture of an insert-carrying oligo and linearized plasmid DNA [Mandecki, Proc. Natl. Acad. Sci. USA 83 (1986) 7177-7181]. The nucleotide (nt) sequences are inserted between two FokI restriction nuclease sites in one of four pUC-derived plasmids. Since FokI makes a staggered ds break at a DNA site 9 and 13 nt away from its recognition site, upon cleavage of the plasmid DNA with FokI, a restriction fragment is liberated that by design contains unique 4-nt-long 5'-protruding ends. The uniqueness of ends permits efficient and directed simultaneous ligation of several restriction fragments to form a gene. The method offers flexibility due to the modular-type assembly and does not require any restriction sites within the constructed gene. The sequence error rate is low: about one error per 4000 bp of DNA cloned. Synthetic DNA for only one DNA strand needs to be provided. The method was applied to the synthesis of a gene fragment encoding the N-terminal 143 amino acid residues of the human immunodeficiency virus transmembrane protein (p41).


Hyperglycemia is associated with poor outcomes in surgical critically ill patients receiving parenteral nutrition.
Hyperglycemia, a major side effect of patients receiving total parenteral nutrition (PN), is associated with higher mortality in critically ill patients. The aim of this study was to determine whether elevated blood glucose levels would be associated with worse outcomes in patients receiving PN. This retrospective study included postoperative patients admitted to our surgical intensive care unit (SICU) from July 2008 to June 2009. Data collected included blood glucose levels, length of stay, and outcome measures. Correlations among daily average, maximum, and minimum blood glucose levels and outcome measures were calculated. Sixty-nine patients were enrolled and divided into PN (n = 40) and non-PN (n = 29) groups. The initial mean blood glucose levels were 138.4 ± 63.1 mg/dL and 123.2 ± 41.8 mg/dL for the PN and non-PN groups, respectively. The mean blood glucose concentration was significantly increased (ΔBS = 44.8 ± 57.3 mg/dL; p < 0.001) in the PN group compared with the non-PN group (ΔBS = 39.4 ± 67.0 mg/dL; p = 0.004). The blood glucose concentration was significantly increased and consequently, consumption of insulin was increased on the 2(nd) day of ICU admission. The risk of mortality increased by a factor of 1.3 (OR = 1.30, 95% CI = 1.07-1.59, p = 0.010) for each 10 mg/dL increase in blood glucose level, when the daily maximum blood glucose level was >250 mg/dL. There were no cases of mortality in the current study when the blood glucose levels were controlled below 180 mg/dL. The mean blood glucose level in patients receiving PN was higher in those with diabetes than in those without diabetes (215.5 ± 42.8 vs. 165.8 ± 42.0 mg/dL, respectively, p = 0.001). The blood glucose level was associated with patient outcome and should be intensively monitored in critically ill surgical patients. We suggest that blood glucose levels should be controlled below 180 mg/dL in postoperative critically ill patients.


Retraction: Intrathecal dextmedetomidine to reduce shoulder tip pain in laparoscopic cholecystectomies under spinal anesthesia.
[This retracts the article on p. 320 in vol. 9, PMID: 26712967.].


Preliminary study of quantification of regurgitant volume in mitral regurgitation by color Doppler echocardiography.
A method for quantification of regurgitant volume in mitral regurgitation (MR) was studied. 31 cases of MR were investigated with color Doppler. The reliability of measuring velocity by Doppler and the influence of pressure gradient on MR were assessed and confirmed by experimental device. The results suggested that the best method in quantification of the regurgitant volume was "calibrating method" (r = 0.99; P less than 0.01), the next to the best was "volume method" (r = 0.74; P less than 0.01), whereas the regurgitant volume evaluated by multiplication of area, velocity and time was far from the actual regurgitant volume (r = 0.47; P greater than 0.05). The velocity of blood flow measured by Doppler is closely correlated to results obtained from experiments (r = 0.69; P less than 0.05). We believe that the ratio of back flow area and average area of left atrium calculated by Helmcke's method reflects the severity of the disease to a certain degree, bu there are many problems unsolved, e.g. the determination of the velocity of blood flow by color Doppler is dependent on the degree of brightness of coloration; the brighter the color, the quicker the speed it represents, whereas the darker coloration speaks for slower speed.


Effect of ethanol on the Na(+)- and the Na+,K(+)-ATPase activities of basolateral plasma membranes of kidney proximal tubular cells.
The Na(+)- and the Na+,K(+)-ATPase activities of basolateral plasma membranes from rat kidney proximal tubular cells were affected differentially by ethanol. Moreover, at concentrations of ethanol that can be reached in vivo in the blood plasma (50 mM) there was a significant effect on the Na(+)-ATPase activity and practically no effect on the Na+,K(+)-ATPase activity.


Serum pepsinogen I levels in patients with non-ulcer dyspepsia.
In order to understand whether the serum pepsinogen I (PGI) levels of non-ulcer dyspepsia (NUD) patients differed from those of healthy controls and which kinds of factors might influence these levels of the former, serum PGI levels were determined by radio-immunoassay in 120 healthy controls and 361 NUD patients. The mean serum PGI level was significantly lower in NUD patients than in the controls (75.8 +/- 38.2 ng/mL versus 95.9 +/- 39.3 ng/mL; P less than 0.0001); in NUD patients, it was significantly higher in males than in females (79.6 +/- 40.4 ng/mL versus 63.2 +/- 26.4 ng/mL; P less than 0.001). However, corrected serum PGI levels according to the lean body mass disclosed no sex difference. Nevertheless, there was a weak correlation between the ages of patients and serum PGI levels (r = 0.403). The serum PGI levels in blood groups A, B, AB and O did not differ significantly. Smoking might be a decisive factor, for the mean serum PGI level was significantly higher among the smokers than among the non-smokers (86.7 +/- 44.6 ng/mL versus 70.6 +/- 33.7 ng/mL; P less than 0.001). It is concluded that the mean serum PGI level of NUD patients, while affected by sex, age, smoker status and the body size, is lower than that of the healthy controls. Without endoscopy, assay of serum PGI level has no place in the diagnosis of dyspepsia because of the wide overlapping of serum PGI levels between NUD patients and patients with other common gastric lesions.


Region-specific glucocorticoid receptor promoter methylation has both positive and negative prognostic value in patients with estrogen receptor-positive breast cancer.
The glucocorticoid receptor (NR3C1, GR) is frequently downregulated in breast tumors, and evidence suggests it acts as a tumor suppressor in estrogen receptor-positive (ER+) breast cancer. We previously found that methylation of the GR promoter CpG island represses gene expression and occurs in ER+ breast tumors. In this study, the prognostic and predictive value of GR methylation was examined in ER+ patients from the CCTG MA.12 clinical trial of tamoxifen versus placebo in women with early breast cancer. We developed a targeted multiplex bisulfite next-generation sequencing assay to detect methylation at multiple GR promoter regions in DNA from formalin-fixed paraffin-embedded (FFPE) samples. Following validation in a small cohort of breast tumors, ER+ FFPE tumor samples from MA.12 (n = 208) were tested. Survival analyses evaluated the impact of GR promoter methylation on patient overall survival (OS) and disease-free survival (DFS). An analysis of TCGA data found that GR methylation is prevalent in ER+ tumors and is associated with decreased gene expression and analysis of public microarray data (KM Plotter) linked decreased GR expression to a poor outcome. In MA.12, two GR promoter regions (U and C) each had prognostic value, but with opposite effects on the outcome. U methylation was associated with poor OS (HR = 1.79, P = 0.041) whereas C methylation was associated with better OS (HR = 0.40, P = 0.040) and DFS (HR = 0.49, P = 0.037). The classification of patients based on the methylation status of the two regions was prognostic for OS (P = 0.006) and DFS (P = 0.041) and revealed a group of patients (U methylated, C unmethylated) with very poor outcomes. Placebo-treated patients in this high-risk group had worse OS (HR = 2.86, P = 0.002) and DFS (HR = 2.09, P = 0.014) compared to the rest of the cohort. Region-specific GR promoter methylation was an independent prognostic marker for patient survival and identified a subset of patients with poor prognosis, particularly without tamoxifen treatment. These findings provide a foundation for future studies into GR methylation as a promising prognostic biomarker in ER+ breast cancer.


Immediate emergency department external cardiac pacing for prehospital bradyasystolic arrest.
Approximately 25% of patients in prehospital cardiac arrest present in bradyasystolic rhythms, and their long-term prognosis is very poor. Our study was undertaken to determine the utility of immediate emergency department (ED) external cardiac pacing in this situation. Twenty patients presenting with bradyasystolic prehospital cardiac arrest were entered in the study. All received the usual advanced cardiac life support therapy, but also were externally paced immediately using an automated external defibrillator and pacemaker (AEDP). Only two of 20 patients showed evidence of electrical capture, and none developed pulses with pacing. Four of the 20 patients developed a sinus rhythm and blood pressure during resuscitation. Three survived to leave the ED, but none survived to leave the hospital. An increase in the rate of bradycardia and pulseless idioventricular rhythms that was independent of electrical capture or pharmacologic therapy was noted occasionally. Although survival was not enhanced using the AEDP, the device was reliable, easy to use, and free of complications. External cardiac pacing warrants further investigation in the prehospital setting.


Physiology of breathing and related pathological processes in infants.
There is little information describing control of breathing in the fetus and infant. The available data have largely been drawn from studies in animals and awake adults. Although the hierarchy of control of breathing is the same in adults and infants, feedback emphasis is different, with behavioral states and the sleep/wake cycle primary in the fetus and infant and integrated chemoreceptor response primary in the older child and adult. Control of breathing during the transition from the fetal state to a breathing child and the process of maturation are very different from that in adults. The article begins with an overview of the changes in the systems responsible for breathing at the developmental stages from fetus to neonate, with differences highlighted. It then discusses the possible pathology related to difficulties in negotiating this transition period, including apnea, sudden infant death syndrome, and chemoreceptor control abnormalities.


Treatment of trapeziometacarpal arthritis: results of resection arthroplasty.
Ninety-one thumbs with symptomatic trapeziometacarpal arthritis were studied and classified by the severity of trapeziometacarpal arthritis, as seen on the roentgenogram. Thirty-five patients with mild changes had satisfactory relief of pain after treatment with anti-inflammatory drugs and a C-splint. Operation, consisting of resection of the trapezium and shortening by 1.5 cm of the abductor pollicis longus tendon was performed on 16 thumbs. In six patients a rolled palmaris longus tendon was inserted between the metacarpal base and the scaphoid. All patients had relief of pain, improvement of pinch and grip strength, and an increased range of thumb pronation after operation. There was no difference in the results of those patients treated with or without tendon interposition. Trapezial resection was found to be an effective means of treating patients with symptomatic trapeziometacarpal arthritis who failed to improve with conservative care.


Synthesis, characterization, and evaluation of chloroaluminium phthalocyanine incorporated in poly(ε-caprolactone) nanoparticles for photodynamic therapy.
The use of nanotechnology has been widely used in biomedical science, including orthopedic implants, tissue engineering, cancer therapy and drug elution from nanoparticle systems, such as poly-caprolactone (PCL) nanoparticles, which stand out mainly for their biocompatibility, being considered as effective carriers for photosensitizing drugs (PS) in photodynamic therapy (PDT) protocols. This manuscript describes the synthesis and characterization of PCL nanoparticles for controlled release of the drug chloro-aluminum phthalocyanine (ClAlPc) as a photosensitizer for application in PDT. The PCL-ClAlPc nanoparticles were developed by the nanoprecipitation process. The structure and morphology of the nanoparticles were studied with scanning electron microscopy (SEM) and with Fourier transform infrared (FTIR). The size of nanomaterials was studied using the Dynamic Light Scattering (DLS) method. Photophysical and photochemical characterizations were performed. Subsequently, photobiological studies were also used to characterize the system. The nanoparticles had an average diameter of 384.7 ± 138.6 nm and a polydispersity index of 0.153. SEM analysis revealed that the system formed a spherical shape typical of these delivery systems. Charging efficiency was 82.1% ± 1.2%. The phthalocyanine-loaded PCL nanoparticles maintained their photophysical behavior after encapsulation. Cell viability was determined after the dark toxicity test, and it was possible to observe that there was no evidence of toxicity in the dark, for all concentrations tested. The assay also revealed that adenocarcinoma cells treated with free ClAlPc and in the nanoformulation showed 100% cell death when subjected to PDT protocols. The intracellular location of the photosensitizer indicated a high potential for accumulation in the cytoplasm and nucleus. From the photophysical, photochemical and photobiological analyzes obtained, it was possible to observe that the development of PCL nanoparticles encapsulated with ClAlPc, by the nanoprecipitation method was adequate and that the in vivo release study is efficient to reduce the release rate and attenuate the burst of PS loaded on PCL nanoparticles. The results reinforce that the use of this system as drug delivery systems is useful in PDT protocols.


Rate of dilution and redox ratio influence the refolding efficiency of recombinant fungal dehydrogenases.
Dehydrogenases from fungi are attracting attention as industrial biocatalysts due to their high activity and chiral selectivity. However, these enzymes form insoluble aggregates when overexpressed in E. coli, limiting their industrial application. In the present study, we report the systematic development of a refolding process for selected, industrially relevant fungal dehydrogenases, viz., formate dehydrogenase from Candida boidinii (CbFDH) and formate and alcohol dehydrogenases from Geotrichum candium (GcFDH and GcADH, respectively). We first employed a screen to evaluate the effects of different variables on refolding including the buffer system, additives, and rate of dilution. The extent of refolding was determined by enzyme assays, circular dichroism, and tryptophan fluorescence. Our results showed that glycerol and reducing environment are essential for refolding of these dehydrogenases. Further, slow dilution of solubilized protein over 16 h dramatically improved the recovery of refolded enzymes compared to rapid dilution. The importance of slow dilution was further confirmed in a 10-fold scaled-up refolding trial. Overall, we demonstrate a robust method for refolding of fungal dehydrogenases, thus improving their availability for various biocatalytic applications.


Comparing different spatio-temporal modeling methods in dengue fever data analysis in Colombia during 2012-2015.
In this paper, we compare a variety of spatio-temporal conditional autoregressive models to a dengue fever dataset in Colombia, and incorporate an innovative data transformation method in the data analysis. In order to gain a better understanding on the effects of different niche variables in the epidemiological process, we explore Poisson-lognormal and binomial models with different Bayesian spatio-temporal modeling methods in this paper. Our results show that the selected model can well capture the variations of the data. The population density, elevation, daytime and night land surface temperatures are among the contributory variables to identify potential dengue outbreak regions; precipitation and vegetation variables are not significant in the selected spatio-temporal mixed effects model. The generated dengue fever probability maps from the model show a geographic distribution of risk that apparently coincides with the elevation gradient. The results in the paper provide the most benefits for future work in dengue studies.


Natural selection has driven the recurrent loss of an immunity gene that protects Drosophila against a major natural parasite.
Polymorphisms in immunity genes can have large effects on susceptibility to infection. To understand the origins of this variation, we have investigated the genetic basis of resistance to the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster. We found that increased expression of the gene lectin-24A after infection by parasitic wasps was associated with a faster cellular immune response and greatly increased rates of killing the parasite. lectin-24A encodes a protein that is strongly up-regulated in the fat body after infection and localizes to the surface of the parasite egg. In certain susceptible lines, a deletion upstream of the lectin-24A has largely abolished expression. Other mutations predicted to abolish the function of this gene have arisen recurrently in this gene, with multiple loss-of-expression alleles and premature stop codons segregating in natural populations. The frequency of these alleles varies greatly geographically, and in some southern African populations, natural selection has driven them near to fixation. We conclude that natural selection has favored the repeated loss of an important component of the immune system, suggesting that in some populations, a pleiotropic cost to lectin-24A expression outweighs the benefits of resistance.


The segmental distribution of cervical range of motion: A comparison of ACDF versus TDR-C.
This study was a retrospective radiographic evaluation of patients after cervical total disc replacement (TDR-C) or anterior cervical discectomy and fusion (ACDF) for one-level cervical disc disease. Our objective was to evaluate (1) total cervical (C1-C7) range of motion (ROM) during dynamic imaging, and (2) relative contribution to total cervical ROM from operative and adjacent levels. Radiographic review of 64 patients who underwent TDR-C (n = 30) or ACDF (n = 34) for one-level cervical disc disease. ROM measurements were performed independently using a vertebral motion analysis system to evaluate total cervical ROM and relative contribution to total ROM from each level (C1-C7) preoperatively and at 12-month follow-up. At follow-up, TDR-C patients had significantly greater improvement in total cervical ROM (+5.67°, 1.15 mm) than ACDF patients (-0.96°, 0.12 mm) (P = 0.001). In TDR-C patients, relative contributions to total cervical ROM from operative and adjacent caudal and cranial levels were statistically equivalent to baseline values. ACDF patients had a significantly reduced contribution to total cervical ROM from the operative level (-22.5%, P < 0.001) and significantly elevated contributions from the adjacent caudal level (+16.5%-21.3%, P < 0.001) and from the adjacent first (20.6% vs. 34.6%, P < 0.001), second (22.9% vs. 30.4%, P < 0.001), and third cranial levels (17.5% vs. 25.6%, P < 0.001). The cervical spine compensates for loss of ROM at the operative level in ACDF patients. However, total cervical ROM increases with TDR-C and maintains physiologic distribution of ROM throughout the cervical spine at 12-month follow-up, potentially reducing the risk for adjacent segment breakdown.


Undernutrition in elective colorectal surgery. Implications for post operative morbidity.
The nutritional status of 65 patients undergoing elective colorectal surgery was assessed using 5 conventional nutritional indices, percentage ideal weight, mid arm muscle circumference, triceps skin fold thickness, serum albumin and serum total iron binding capacity. Only 9 patients had values for all five indices which are taken to represent normal nutritional status. This survey suggests that many patients undergoing elective colorectal surgery in this country have subnormal values of the indices commonly used for nutritional assessment but only severe depression of serum albumin however appears to adversely affect the outcome of surgery.


Amplitude synchronization of spontaneous activity of medial and lateral temporal gyri reveals altered thalamic connectivity in patients with temporal lobe epilepsy.
In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23-69) and 16 controls (age 21-35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject's T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual regression analysis was applied on preprocessed rsfMRI data to detect amplitude synchronization of medial and lateral temporal segments with the rest of the brain. We calculated the overlapped volume ratio of synchronized voxels within specific target regions including the thalamus (total and bilateral). A general linear model was used with Bonferroni correction for covariates of epilepsy duration and age of patient at scan to statistically compare synchronization in patients with mTLE with MTS and controls, as well as with respect to whether patients remained seizure-free (SF) or not (NSF) after receiving epilepsy surgery. We found increased ipsilateral positive connectivity between the LTLs and the thalamus and contralateral negative connectivity between the MTLs and the thalamus in patients with mTLE with MTS compared to controls. We also found increased asymmetry of functional connectivity between temporal lobe subregions and the thalamus in patients with mTLE with MTS, with increased positive connectivity between the LTL and the lesional-side thalamus as well as increased negative connectivity between the MTL and the nonlesional-side thalamus. This asymmetry was also seen in NSF patients but was not seen in SF patients and controls. Amplitude synchronization was an effective method to detect functional connectivity alterations in patients with mTLE with MTS. Patients with mTLE with MTS overall showed increased temporal-thalamic connectivity. There was increased functional involvement of the thalamus in MTS, underscoring its role in seizure spread. Increased functional thalamic asymmetry patterns in NSF patients may have a potential role in prognosticating patient response to surgery. Elucidating regions with altered functional connectivity to temporal regions can improve understanding of the involvement of different regions in the disease to potentially target for intervention or use for prognosis for surgery. Future studies are needed to examine the effectiveness of using patient-specific abnormalities in patterns to predict surgical outcome.


Magnetically induced chessboard pattern in the conductance of a Kondo quantum dot.
We quantitatively describe the main features of the magnetically induced conductance modulation of a Kondo quantum dot-or chessboard pattern-in terms of a constant-interaction double quantum dot model. We show that the analogy with a double dot holds down to remarkably low magnetic fields. The analysis is extended by full 3D spin density functional calculations. Introducing an effective Kondo coupling parameter, the chessboard pattern is self-consistently computed as a function of magnetic field and electron number, which enables us to explain our experimental data quantitatively.


Economic and clinical burdens and associated health disparities in HIV/AIDS management using big data: potentially inappropriate use and deprescribing of benzodiazepines.
This study aimed to examine factors, healthcare utilization, and medical costs associated with potentially inappropriate use of benzodiazepines in persons living with HIV (PLWH). We used big data from Medicare claims in 2017. Potentially inappropriate use of benzodiazepines was defined as having any benzodiazepine claims in individuals 65+ years or having benzodiazepine claims for more than four weeks in individuals 18-64 years. Logistic regressions, zero-inflated negative binomial regressions, and generalized linear models were used. This study included 1,211 PLWH and 235 (19.41%) had potentially inappropriate use of benzodiazepines. PLWH who were 65+ years (OR: 0.56; 95% CI: 0.33, 0.96), non-Hispanic blacks (OR: 0.29; 95% CI: 0.20, 0.41), or Hispanics (OR: 0.55; 95% CI: 0.35, 0.88) were less likely to use benzodiazepines inappropriately. PLWH who had potentially inappropriate use of benzodiazepines had more inpatient (IRR: 1.46; 95% CI: 1.10, 1.94), outpatient (IRR: 1.14; 95% CI 1.02, 1.28), and emergency room (IRR: 1.32; 95% CI: 1.03, 1.68) visits. Potentially inappropriate use of benzodiazepines was associated with higher total (β: 0.16; 95% CI: 0.07, 0.25), Medicare (β: 0.18; 95% CI: 0.07, 0.28), and out-of-pocket (β: 0.21; 95% CI: 0.05, 0.36) costs. This study provides real-world evidence to support deprescribing benzodiazepines in PLWH.


HPLC-CAD as a supplementary method for the quantification of related structure impurities for the purity assessment of organic CRMs.
In organic purity assessment, chromatography separation with a suitable detector is required. Diode array detection (DAD) has been a widely used technique for high-performance liquid chromatography (HPLC) analyses, but its application is limited to compounds with sufficient UV chromophores. Charged aerosol detector (CAD), as a mass-dependent detector, is advantageous for providing a nearly uniform response for analytes, regardless of their structures. In this study, 11 non-volatile compounds with/without UV chromophores were analyzed by CAD using continuous direct injection mode. The RSDs of CAD responses were within 17%. For saccharides and bisphenols, especially, the RSDs were lower (2.12% and 8.14%, respectively). Since bisphenols exist in UV chromophores, their HPLC-DAD responses were studied and compared with CAD responses, with CAD showing a more uniform response. Besides, the key parameters of HPLC-CAD were optimized and the developed method was verified using a Certified Reference Material (CRM, dulcitol, GBW06144). The area normalization result of dulcitol measured by HPLC-CAD was 99.89% ± 0.02% (n = 6), consistent with the certified value of 99.8% ± 0.2% (k = 2). The result of this work indicated that the HPLC-CAD method could be a good complementary tool to traditional techniques for the purity assessment of organic compounds, especially for compounds lacking UV chromophores.


Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis.
Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2-mutants that express different amounts of TPPI activity to benchmark levels required for therapeutic benefits. Approximately 3% of normal TPPI activity in brain delayed disease onset and doubled lifespan to a median of approximately 9 months compared to mice expressing approximately 0.2% of normal levels. Expression of 6% of normal TPPI activity dramatically attenuated disease, with a median lifespan of approximately 20 months which approaches that of unaffected mice. While the lifespan of this hypomorph is shortened, disease is late-onset, less severe and progresses slowly compared to mice expressing lower TPPI levels. For gene therapy and other approaches that restore enzyme activity, these results suggest that 6% of normal TPPI activity throughout the CNS of affected individuals will provide a significant therapeutic benefit but higher levels will be required to cure this disease.


Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.
A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell line and stavudine ester bearing piperazine acetic acid was found to be the most potent compound with a selective index of >15,723. Stavudine prodrug bearing ciprofloxacin and norfloxacin acetic acid showed 100% inhibition against Mycobacterium tuberculosis H(37)Rv at 6.25 microg/mL. The prodrugs also exhibited antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t(1/2) ranging from 20-240 min.


Simultaneous nitrification-denitrifying phosphorus removal (SNDPR) at low DO for treating carbon-limited municipal wastewater.
This study investigated simultaneous nitrification-denitrifying phosphorus removal in a sequencing batch reactor (SBR) activated sludge process. The process consisted of an extended anaerobic period (180 min) followed by a low DO (0.3 ± 0.05 mg/L) simultaneous nitrification-denitrifying phosphorus removal. The reactor was operated within a wide range of COD/N ratio (5-10) without any volatile fatty acids (VFA) supplementation. N and P removal efficiencies were as high as 91% and 96%, respectively. The process was efficient even at a very low COD /N ratio of 5, with N and P removal efficiencies of 70% and 90%, respectively. The N and P removal efficiencies improved to more than 90% at a COD/N ratio 8. It was found that the initial filtered flocculated COD (ffCOD)/[total oxidized Kjeldahl Nitrogen (TKNoxidized) + NOx-Nintitial] ratio in the reactor played a significant role in the process efficiency. It was observed that N-removal efficiency decreased with a decrease of [ffCODinitial/ (TKNoxidized + NOx-Ninitial)] ratio even at high COD/N ratio of 10. Simultaneous nitrification denitrification (SND) efficiencies varied between 60%-88% depending on the influent COD/N ratio and [ffCODinitial/ (TKNoxidized + NOx-Ninitial)] ratio in the reactor. Cyclic studies showed a distinct two step phosphorus release in the extended anaerobic period in contrast to the more conventional single step phosphorus release. During the aerobic period, low DO favored denitrifying P-removal without significant accumulation of NO3-N, and NO2-N until all endogenous carbon was consumed. Denitrifying phosphorus accumulating organisms (DPAOs) played a vital role in simultaneous denitrification and phosphorus removal. Aerobic and anoxic P-removal represented about 55% and 45% of the overall phosphorus removal, respectively. Cycle tests showed that DPAOs have a competitive advantage over NOB for nitrite consumption at low DO. The process was found to be carbon efficient as evidenced by the COD/NOx-N ratio of 4.2 for denitrification. Compared to traditional enhanced biological phosphorus removal (EBPR) coupled with exogenous denitrification, this process reduces carbon and oxygen demand for combined N and P removal from municipal wastewater by about 45%, and 35% respectively.


Uncertainty-aware domain alignment for anatomical structure segmentation.
Automatic and accurate segmentation of anatomical structures on medical images is crucial for detecting various potential diseases. However, the segmentation performance of established deep neural networks may degenerate on different modalities or devices owing to the significant difference across the domains, a problem known as domain shift. In this work, we propose an uncertainty-aware domain alignment framework to address the domain shift problem in the cross-domain Unsupervised Domain Adaptation (UDA) task. Specifically, we design an Uncertainty Estimation and Segmentation Module (UESM) to obtain the uncertainty map estimation. Then, a novel Uncertainty-aware Cross Entropy (UCE) loss is proposed to leverage the uncertainty information to boost the segmentation performance on highly uncertain regions. To further improve the performance in the UDA task, an Uncertainty-aware Self-Training (UST) strategy is developed to choose the optimal target samples by uncertainty guidance. In addition, the Uncertainty Feature Recalibration Module (UFRM) is applied to enforce the framework to minimize the cross-domain discrepancy. The proposed framework is evaluated on a private cross-device Optical Coherence Tomography (OCT) dataset and a public cross-modality cardiac dataset released by MMWHS 2017. Extensive experiments indicate that the proposed UESM is both efficient and effective for the uncertainty estimation in the UDA task, achieving state-of-the-art performance on both cross-modality and cross-device datasets.


Factors affecting tobacco, nicotine, and cannabis product use among California young adults during the COVID-19 pandemic: A qualitative study.
The effects of COVID-19 on tobacco and cannabis use have been variable, and it is unclear the extent to which factors affecting changes in tobacco and cannabis use differ. The purpose of this study was to identify the COVID-19-related factors that affect changes in tobacco and cannabis use during the pandemic. Focus groups with 114 young adults in California in April 2021 were held to discuss tobacco and cannabis use patterns, adverse events, and the effect of COVID-19 on tobacco and cannabis product use. Factors affecting changes in use were largely similar between tobacco products and cannabis products. Increases in product use were a result of changing social environment, coping with emotional and psychological distress, and product related factors. Decreases in product use were a result of social isolation, COVID-19-related health concerns, disruptions in daily patterns of living, and reduced access. Drivers of increased cannabis use distinct from tobacco or nicotine product use included feeling greater freedom to disengage and perceptions of less harm. Improved understanding of how the pandemic has affected tobacco and cannabis use can inform tailored interventions to both support those who have decreased or quit and assist those who have increased use during the pandemic to reduce or cease their consumption.


Cardiac retransplantation in childhood: analysis of data from the United Network for Organ Sharing.
For children in whom graft failure develops after cardiac transplantation, retransplantation is often considered. Although some centers have reported equivalent results for retransplantation as for primary transplantation, this strategy remains controversial. We sought to examine outcomes after retransplantation in children and to identify risk factors for mortality. United Network for Organ Sharing records of heart transplantation for subjects younger than 18 years from 1987 to 2004 were reviewed. Indications for retransplantation and patient characteristics were evaluated. Analysis was performed with proportional hazards regression, controlling for other potential risk factors. Among the 4227 pediatric heart transplants, there were 219 retransplants. The most common indication for retransplantation was coronary allograft vasculopathy (51%). The mean interval from initial heart transplant to retransplantation was 4.7 +/- 3.8 years. Forty-two retransplants (19%) were performed within 180 days of primary transplantation. Survivals at 1, 5, and 10 years after retransplantation were 79%, 53%, and 44%, respectively. In multivariate analysis, retransplantation was associated with significantly higher mortality than primary transplantation (odds ratio 1.67, 95% confidence interval 1.32-2.12, P < .001). Patients who underwent retransplantation within 180 days of primary transplantation had a significantly lower 1-year survival than did other retransplant recipients (53% vs 86%, respectively, P < .02). Subjects who required mechanical ventilation before retransplantation also had poorer survival (P < .03). Survival after cardiac retransplantation in children is inferior to that after primary transplantation. Although results are acceptable, the impact of retransplantation on the availability of donor hearts requires further consideration.


[Clinical and pathophysiological contribution of OCT-angiography to epiretinal membranes].
Epiretinal membranes may lead to centripetal contraction forces on the retina and its vessels. OCT-Angiography (OCT-A) is a recent tool which permits a non-invasive understanding of these vascular changes. This review focuses on the OCT-A findings in idiopathic epiretinal membranes, before and after surgery, and the role of internal limiting membrane peeling. It appears that contraction of the epiretinal membrane is associated with both a reduction in the area and perimeter of the foveal avascular zone and alterations in the superficial and deep capillary plexuses. These changes mainly reflect a vascular shift from the perifoveal to the foveal region, increasing with retinal deformation, but also probable dynamic changes in vascular flow. Membrane peeling allows at least partial improvement of these microvascular parameters. Nevertheless, some limitations of OCT-A, such as segmentation errors on a retina with highly modified architecture, can lead to a selection bias in the studies and should call for caution in the interpretation of the results. Finally, internal limiting membrane peeling contributes to changes in the retinal architecture after surgery, in particular by causing a centripetal movement of the macular capillaries and a displacement of the fovea toward the optic nerve head. This role should be clarified in future studies.


Eimeria spp. (Eimeriidae) in the migratory whooper swan (Cygnus cygnus) Linnaeus, 1758 (Anatidae) from Sanmenxia Swan Lake National Urban Wetland Park in the middle reaches of the Yellow River in China.
This study i dentifies four Eimeria spp. recorded from fecal samples of migratory whooper swans (Cygnus cygnus) in Sanmenxia Swan Lake National Urban Wetland Park in Sanmenxia city in the middle reaches of the Yellow River, China. Eimeria hermani, Eimeria nocens, Eimeria stigmosa, and Eimeria magnalabia were compatible in all characteristic features with their respective original descriptions. In addition to the preliminary morphological identification, this study provides a preliminary genotypic identification of these four Eimeria spp. via sequencing of the 18S rRNA, 28S rRNA, and COI gene loci that are suitable for the genotypic differentiation of these coccidia. This is the first report of molecular data for the four Eimeria spp. in migratory whooper swans. Finally, this study discusses the environmental risks of these coccidia for migratory whooper swans in Sanmenxia Swan Lake National Urban Wetland Park.


Euthanasia in psychiatry can never be justified. A reply to Wijsbek.
In a recent article, Henri Wijsbek discusses the 1991 Chabot "psychiatric euthanasia" case in the Netherlands, and argues that Chabot was justified in helping his patient to die. Dutch legislation at the time permitted physician assisted suicide when the patient's condition is severe, hopeless, and unbearable. The Dutch Supreme Court agreed with Chabot that the patient met these criteria because of her justified depression, even though she was somatically healthy. Wijsbek argues that in this case, the patient's integrity had been undermined by recent events, and that this is the basis for taking her request seriously; it was unreasonable to expect that she could start again. In this paper, I do not challenge the Dutch euthanasia criteria in the case of somatic illness, but I argue that both Chabot and Wijsbek are wrong because we can never be sufficiently confident in cases of severe exogenous depression to assist the patient in her irreversible act. This is partly because of the essential difference between somatic and mental illness, and because of the possibility of therapy and other help. In addition, I argue that Wijsbek's concept of integrity cannot do the work that he expects of it. Finally, I consider a 2011 position paper from the Royal Dutch Medical Association on euthanasia, and the implications it might have for Chabot-style cases in the future.


Alternative Hfq-sRNA interaction modes dictate alternative mRNA recognition.
Many bacteria use small RNAs (sRNAs) and the RNA chaperone Hfq to regulate mRNA stability and translation. Hfq, a ring-shaped homohexamer, has multiple faces that can bind both sRNAs and their mRNA targets. We find that Hfq has at least two distinct ways in which it interacts with sRNAs; these different binding properties have strong effects on the stability of the sRNA in vivo and the sequence requirements of regulated mRNAs. Class I sRNAs depend on proximal and rim Hfq sites for stability and turn over rapidly. Class II sRNAs are more stable and depend on the proximal and distal Hfq sites for stabilization. Using deletions and chimeras, we find that while Class I sRNAs regulate mRNA targets with previously defined ARN repeats, Class II sRNAs regulate mRNAs carrying UA-rich rim-binding sites. We discuss how these different binding modes may correlate with different roles in the cell, with Class I sRNAs acting as emergency responders and Class II sRNAs acting as silencers.


Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups.
The naturally occurring sesquiterpene lactone thapsigargin is a potent and selective inhibitor of SERCA ATPases, a family of Ca(2+)-pumping ATPases present in the endoplasmic reticulum of all mammalian cells. We have studied some of the molecular features of thapsigargin responsible for its inhibitory action towards these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the inhibitory potency relative to the parent compound was found ranging from slight to over 3 orders of magnitude. The inhibitory activity showed a very strong configuration dependence, a major contribution from the ester groups at C3 and C10, and an apparently minor contribution from the lactone ring substituents. The data are consistent with thapsigargin fitting to a sterically discriminating cleft involving the hydrophobic transmembrane region of the ATPase, and is compatible with available kinetic evidence of thapsigargin-mediated inhibition.


Islet transplantation: current status and future directions.
Pancreatic islet transplantation has gone a long way to finally enter the armamentarium of today's clinicians for the battle against diabetes. The proof of principle has been made and current clinical islet transplant trials need to further refine this attractive treatment modality. We review the post-Edmonton era, the selection of islet transplant recipients, the production of islet grafts, and the need for immunosuppression and procedure-related risks. The success of islet transplantation and expansion of clinical trials with islet networks are also discussed.


Rates and predictors of visits to primary care physicians during and after treatment of childhood acute lymphoblastic leukemia: A population-based cohort study.
Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL). Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables. A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p < .0001). Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment.


Effect of Age and Refractive Error on the Melanopsin Mediated Post-Illumination Pupil Response (PIPR).
Melanopsin containing intrinsically photosensitive Retinal Ganglion cells (ipRGCs) mediate the pupil light reflex (PLR) during light onset and at light offset (the post-illumination pupil response, PIPR). Recent evidence shows that the PLR and PIPR can provide non-invasive, objective markers of age-related retinal and optic nerve disease; however there is no consensus on the effects of healthy ageing or refractive error on the ipRGC mediated pupil function. Here we isolated melanopsin contributions to the pupil control pathway in 59 human participants with no ocular pathology across a range of ages and refractive errors. We show that there is no effect of age or refractive error on ipRGC inputs to the human pupil control pathway. The stability of the ipRGC mediated pupil response across the human lifespan provides a functional correlate of their robustness observed during ageing in rodent models.


Effect of Dissolved Oxygen and Immersion Time on the Corrosion Behaviour of Mild Steel in Bicarbonate/Chloride Solution.
The electrochemical behavior of mild steel in bicarbonate solution at different dissolved oxygen (DO) concentrations and immersion times has been studied under dynamic conditions using electrochemical techniques. The results show that both DO and immersion times influence the morphology of the corrosion products. In comparative tests, the corrosion rate was systematically found to be lower in solutions with lower DO, lower HCO₃- concentrations and longer immersion time. The SEM analyses reveal that the iron dissolution rate was more severe in solutions containing higher DO. The decrease in corrosion rate can be attributed to the formation of a passive layer containing mainly α -FeO (OH) and ( γ -Fe₂O₃/Fe₃O₄) as confirmed by the X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). Passivation of mild steel is evident in electrochemical test at ≈ -600 mVSCE at pH ≥ 8 in dearated ( ≤ 0.8 ppm DO) chloride bicarbonate solution under dynamic conditions.


A poor prognosis of a mediastinal bronchogenic cyst with malignant transformation: A case report.
Bronchogenic cysts (BC) are congenital lesions, it results from an abnormal budding of the tracheobronchial tree. Malignant transformation is very rare. We report a case of adenocarcinoma arising in a BC of the posterior mediastinum detected after surgery. We report the case of a 32-year-old man, without a particular medical history. The patient presented a cough associated with dyspnea, and a weight loss 4-month before the diagnosis. The imaging tools, showed a voluminous latero-tracheal mass of the posterior mediastinum. The diagnoses of a neurogenic tumor or a BC were suspected. The patient was treated by video-assisted thoracoscopy. Complete excision was done complicated by lesion's small rupture. The microscopic exam revealed unfortunately an adenocarcinoma arising in a BC. The patient had started the cure of chemotherapy. Six months later, the patient died due to tumor recurrence with cerebral metastasis. Mediastinum BC, is usually located within the middle and posterior mediastinum. This condition is a benign congenital lesion. His curative therapy was a complete surgical resection with a good prognosis. However, malignant transformation may seldom occur and is most often accidentally diagnosed during the histological examination of specimens. In this case, the surgical treatment may be insufficient, and the prognosis may be poor. Malignant degeneration of mediastinal BC, despite being rare, should be kept in mind, carefully avoided and managed.


Comparative studies on the efficacy of sulphachlorpyrazine and toltrazuril for the treatment of caecal coccidiosis in chickens.
The therapeutic efficacy of sulphachlorpyrazine and toltrazuril against experimentally induced Eimeria tenella infection was compared in battery and floor pen raised broiler chickens. In the battery studies, both drugs prevented coccidiosis-related mortality and decrease of weight gain to a similar degree, but toltrazuril was more effective in reducing intestinal lesions and faecal scores, when treatments were initiated 24 h postinfection. When medication was delayed until 72 h after inoculation, the sulphonamide proved to be more effective in preventing reduction of weight gain and intestinal lesions caused by the parasites. Under simulated use conditions both drugs showed an appropriate anticoccidial efficacy without major differences between them.


Convergent extension in mammalian morphogenesis.
Convergent extension is a fundamental morphogenetic process that underlies not only the generation of the elongated vertebrate body plan from the initially radially symmetrical embryo, but also the specific shape changes characteristic of many individual tissues. These tissue shape changes are the result of specific cell behaviors, coordinated in time and space, and affected by the physical properties of the tissue. While mediolateral cell intercalation is the classic cellular mechanism for producing tissue convergence and extension, other cell behaviors can also provide similar tissue-scale distortions or can modulate the effects of mediolateral cell intercalation to sculpt a specific shape. Regulation of regional tissue morphogenesis through planar polarization of the variety of underlying cell behaviors is well-recognized, but as yet is not well understood at the molecular level. Here, we review recent advances in understanding the cellular basis for convergence and extension and its regulation.


Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A.
Jiyuan Oridonin A (JOA) is a naturally occurring ent-kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA, the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC50 value of 0.39 ± 0.09 μM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12-induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA, which would contribute to its further development as an antitumor agent.


Suppression of delayed type hypersensitivity induction to sheep red blood cells by concanavalin A in mice.
An examination was carried out on the in vivo effect of concanavalin A (Con A) on the induction of delayed-type hypersensitivity (DTH) to heterologous erythrocytes in mice. DTH induction was suppressed by an intravenous injection of 100 microng of Con A 1 day before, or simultaneously with immunization. This suppression was mediated by Con-A-activated spleen cells, and also by their cell-free extracts. However, this suppressive effect was abrogated by absorption of cell-free extracts with immunoadsorbent composed of rabbit anti-mouse thymocyte serum (ATS), indicating that suppressive factors for DTH induction make up one of the components extractable from Con-A-activated T cell population.


Natural course of pineal cysts-a radiographic study.
Pineal cysts (PCs) are a benign lesion of the pineal gland that have been known to the medical community for a long time. With a prevalence rate of approximately 1% in the general population, PC is often a reason for medical counseling. The natural course of PC morphology has not been well described. In this study, we present a longitudinal magnetic resonance imaging (MRI) study of patients with PCs, with special focus on those who showed an increase or decrease in PC size. We enrolled all patients with a PC who were referred to our department between January 2000 and January 2018. Each patient underwent a clinical examination, and the patient's age, sex, and presenting signs and symptoms were noted. MRI was performed during periodic examinations, and a clinical and radiological course was reassessed. In total, 133 patients (99 women, 34 men) were enrolled. The mean maximum diameter was 12.7 ± 5.2 mm (range 7-35 mm). PCs increased in size during the follow-up in seven patients (5.3%) and decreased in size in 10 (7.5%). The remaining cysts (n = 116, 87.2%) were stable over the follow-up period. Analyzing patients according to cyst size change, we found a significant difference in the mean age between the PC progression group and PC regression group (p = 0.01). The mean size of the PCs at the time of diagnosis did not differ significantly between the two groups (p = 0.81). We diagnosed two cases of pineal apoplexy. We found that PCs are a dynamic structure that may change in size during the patient's lifetime. Patients with an increase in PC size were significantly younger than patients with a decrease in size. Therefore, PC growth in the first, second, and third decennium is normal and does not justify medical intervention. Surgery is indicated in cases of hydrocephalus and Parinaud's syndrome or in atypical cysts when neoplasia is suspected. The size of a PC does not predict PC behavior in terms of a future increase or decrease in size.


miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis.
Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis? In this prospective case-control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal-Wallis test, followed by Benjamini-Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. Only the miRNA miR-532-3p showed significant differences among the analysed groups, being down-regulated in the EIII/IV group compared with the infertile control group, as well as compared with the EI/II group. The enrichment analysis showed that some genes regulated by this miRNA are involved in important pathways for the acquisition of oocyte competence, such as the oxytocin, calcium, Wnt, FoxO, ErbB and Ras signalling pathways, as well as the oocyte meiosis pathway. The present findings bring new perspectives to understanding the follicular microenvironment of infertile women with different stages of endometriosis. It is suggested that the dysregulation of miR-532-3p may be a potential mechanism involved in the aetiopathogenesis of endometriosis-related infertility. Further studies are needed to evaluate these pathways in cumulus cells of infertile women with the disease, as well as their impact on the acquisition of oocyte competence.


Assembly, glycosylation, and secretion of the oligomeric rat prostatic binding protein in Xenopus oocytes.
Prostatic binding protein (PBP), a hormonally controlled oligomeric glycoprotein secreted by the rat ventral prostate, is composed of three different polypeptide chains, C1, C2, and C3. Microinjection of prostate mRNA into Xenopus laevis oocytes results in the synthesis, processing, and correct assembly of these three components, and also in the export of PBP into the medium. The glycosylation of component C3--the only glycopeptide of PBP--by the oocyte enzymes does not lead to the same result as in the native prostate tissue. The intracellular oocyte component contains an incompletely processed oligomannosyl core unit. Upon secretion this sugar core is further processed, probably at random because the carbohydrate chains attached to the exported C3 molecules are heterogeneous; they are also different from the oligosaccharide unit of authentic C3. However, tunicamycin experiments show that glycosylation is neither a prerequisite for secretion nor for the assembly of PBP, at least in oocytes.


The incidence of pediatric malignant soft tissue tumors of the skin and subcutaneous tissue.
Soft tissue tumors are a known, albeit uncommon, cause of cutaneous malignancy in children. Little is known about which types and how frequently these tumors initially present in the skin or subcutis of children. Using data from the 2000-2014 SEER-18 database, we have identified 12 malignant soft tissue tumor types, which initially presented in the skin or subcutis of children in over 50% of cases.


FIP statement of professional standards: the supply of medicines affecting driving performance.
The International Pharmaceutical Federation (Fédération Internationale Pharmaceutique, FIP) has published a statement on medications affecting driving. This statement discusses labeling, professionals' obligations in educating patients and the roles that professional organizations can take to assure that appropriate patient s counseling and education is provided.


Potentiation of platinum analogue cytotoxicity by hyperthermia.
Carboplatin and iproplatin, two new analogues of cisplatin, appear to have comparable activity in the treatment of advanced ovarian cancer, but minimal nephro- and neurotoxicities. Hyperthermia can potentiate the cytoxicity of cisplatin in vitro and in vivo, but systemic treatment with the combination has proven unsafe in patients. To provide the rationale for an alternative approach, we evaluated the relative degree of additivity between hyperthermia and the three platinum analogues in vitro against a human ovarian adenocarcinoma cell line, UACC-66. All drug and heat treatments were simultaneous for 1 h. Platinum analogue concentrations covered a five-log range from 0.001 to 100 micrograms/ml and hyperthermia temperatures included 38.5 degrees, 40 degrees, 41.5 degrees, and 43 degrees C. A tumor clonogenic assay was used to quantitate heat-drug interactive effects against the UACC-66 cells, and statistical analysis was performed using the median-effect equation of Chou. When combined with heat, the in vitro concentrations of the three platinum analogues were between 5% and 25% of those required at 37 degrees C to inhibit 50%-70% of the UACC-66 tumor colony-forming units. For each drug when combined with heat, a 3 degrees C incremental increase in temperature (i.e., from 37 degrees C to 40 degrees C or from 40 degrees C to 43 degrees C) was associated with a ten-fold decrease in ID50 drug concentration. We conclude that the synergistic effects of both carboplatin and iproplatin with hyperthermia at all temperatures above 37 degrees C provide a rationale for design of clinical trials in patients with ovarian cancer using these hyperthermia-drug combinations.


Safety of percutaneous, image-guided biopsy of hepatocellular carcinoma with and without concurrent ablation.
To determine the prevalence of adverse events after image-guided biopsy of histologically proven hepatocellular carcinomas (HCC) using a standardized, indirect access, coaxial biopsy technique. In this IRB-approved, HIPAA compliant, and retrospective study, we evaluated all consecutive adult patients from 2011 to 2016 who underwent image-guided biopsy of HCC with and without concurrent ablation. Tumor seeding was defined as any new lesion along the needle tract on subsequent imaging. Adverse events were graded using both the Clavien-Dindo Complication Classification system and the most recently proposed Society of Interventional Radiology (SIR) Adverse Event Classification System. A total of 383 patients underwent 398 biopsies (64 ± 11 years; 112 women, 271 men). Most patients (282; 71%) underwent concurrent ablation. Adverse events occurred after 18 biopsies (4.5%): 13 were Grade I (Clavien-Dindo) or minor (SIR) and included hematoma (7), hepatic vein thrombus (2), portal vein thrombus (2), moderate pleural effusion (1), and small pneumothorax (1). The remaining 5 (1.3%) adverse events were classified as Grade II-IIIa (Clavien-Dindo) or moderate (SIR) and included hematoma requiring blood products (n = 1), arrhythmia (n = 1), and symptomatic pleural effusions requiring treatment (n = 3). Baseline age, sex, cause of liver disease, HCC diameter, and HCC grade were not associated with adverse events. There were no tumor seeding events after a median follow-up of 611 days (interquartile range of 211-1104). Percutaneous image-guided tissue sampling using a standardized, indirect access, coaxial technique can be performed safely with and without concurrent ablation by trained cross-sectional interventional radiologists at a tertiary liver transplant center.