Will temperature rise change the biochemical alterations induced in Mytilus galloprovincialis by cerium oxide nanoparticles and mercury?
It is known that, for marine coastal ecosystems, pollution and global warming are among the most threatening factors. Among emerging pollutants, nanoparticles (NPs) deserve particular attention as their possible adverse effects are significantly influenced by environmental factors such as salinity, pH and temperature, as well as by their ability to interact with other contaminants. In this framework, the present study aimed to evaluate the potential interactions between CeO2 NPs and the toxic classic metal mercury (Hg), under current and warming conditions. The marine bivalve Mytilus galloprovincialis was used as biological model and exposed to CeO2 NPs and Hg, either alone or in combination, for 28 day at 17 °C and 22 °C. A suite of biomarkers related to energetic metabolism, oxidative stress/damage, redox balance, and neurotoxicity was applied in exposed and non-exposed (control) mussels. The Hg and Ce accumulation was also assessed. Results showed that the exposure to CeO2 NPs alone did not induce toxic effects in M. galloprovincialis. On the contrary, Hg exposure determined a significant loss of energetic metabolism and a general impairment in biochemical performances. Hg accumulation in mussels was not modified by the presence of CeO2 NPs, while the biochemical alterations induced by Hg alone were partially canceled upon co-exposure with CeO2 NPs. The temperature increase induced loss of metabolic and biochemical functions and the effects of temperature prevailed on mussels exposed to pollutants acting alone or combined.


The prophylactic and curative effect of oltipraz in experimental schistosomiasis mansoni in mice.
Effect of oltipraz on immature and mature forms of Schistosoma mansoni in mice experimentally infected with the Egyptian strain of the worms was assessed. The drug was administered to different groups of mice in a single oral dose of 750 mg/kg body weight 2 hours before infection, 7 days and 15 days after infection and in a single oral dose of 500 mg/kg body weight 30 days and 45 days after infection. Oltipraz was found to be active in reducing the number of worms significantly only when administered in a higher dosage 2 hours before infection and 7 days after infection. Thereafter, the parasites were refractory to the drug action until they have reached sexual maturity 45 days post-infection.


Reciprocal midbrain-extended amygdala circuit activity in preclinical models of alcohol use and misuse.
Alcohol dependence is characterized by a shift in motivation to consume alcohol from positive reinforcement (i.e., increased likelihood of future alcohol drinking based on its rewarding effects) to negative reinforcement (i.e., increased likelihood of future alcohol drinking based on alcohol-induced reductions in negative affective symptoms, including but not limited to those experienced during alcohol withdrawal). The neural adaptations that occur during this transition are not entirely understood. Mesolimbic reinforcement circuitry (i.e., ventral tegmental area [VTA] neurons) is activated during early stages of alcohol use, and may be involved in the recruitment of brain stress circuitry (i.e., extended amygdala) during the transition to alcohol dependence, after chronic periods of high-dose alcohol exposure. Here, we review the literature regarding the role of canonical brain reinforcement (VTA) and brain stress (extended amygdala) systems, and the connections between them, in acute, sub-chronic, and chronic alcohol response. Particular emphasis is placed on preclinical models of alcohol use.


Ultraconservative, Fertility Sparing Treatment of Bilateral Borderline Ovarian Tumors: A Case Report of a 26-Year-Old, 0-Gravida with an Endometrioid Borderline Ovarian Tumor of the Right Ovary and a Sero-Mucinous Borderline Ovarian Tumor of the Left Ovary and a Review of the Literature.
Endometrioid borderline ovarian tumors are rare, entailing a lack of data on their natural history as well as the safety of conservative and ultraconservative surgical management, especially in cases with bilateral borderline ovarian tumors including one of endometrioid differentiation. Therefore, we present such a case and provide a review of the literature on endometrioid borderline ovarian tumors. We report the case of a 26-year-old, 0-gravida with an endometrioid borderline ovarian tumor of the right and a sero-mucinous borderline ovarian tumor of the left ovary treated by fertility sparing, ultraconservative surgery with bilateral cystectomy, completed by staging procedures including omentectomy and peritoneal sampling, as well as endometrial sampling by means of curettage. Reviewing the literature and taking into account the course of our case, we propose the feasibility of an ultraconservative management, including endometrial sampling, in young patients with bilateral borderline ovarian tumors including one of endometrioid differentiation who desire to preserve fertility, followed by a closely monitored follow-up.


How does visuospatial attention modulate motor preparation during gait initiation?
Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). These adjustments create the propulsive forces required to reach the steady-state gait at the end of the first step and can be studied by the displacement of the centre of pressure. The objective of this study was to demonstrate that APAs can be modulated by visuospatial attentional processes prior to motor execution. An adaptation of the Posner paradigm was used to assess attention during step initiation. Twelve healthy subjects performed a gait initiation task under three conditions: a no-cue condition (the control experiment), a double-cue condition (alerting attention) and a single-cue condition (orienting attention). The kinetic and kinematic parameters of the APAs and step initiation were recorded. The time to step initiation was significantly shorter in the alerting condition than in the control condition. This effect was associated with the earlier occurrence of APAs. Orienting condition also had an effect and was associated with the modulation of APA errors (defined as a contralateral shift of the CoP on the cue side before corrective shifting to the target side). Behavioural measurements (such as postural preparation of step initiation) may reflect the interaction between attention and locomotion. Our results show that the different components of attention each have a specific influence on step initiation parameters.


Stakeholders' Perspective on Working Towards a Healthy Ageing Society: Evidence from a Rapidly Ageing Context.
The combined demographic and epidemiologic transition may significantly challenge the ageing population, especially with a weak health and non-health supporting system. The study aims to elicit the supply side stakeholders' view on healthy ageing and the readiness for a healthy ageing society in the Kerala context, which is one of India's most advanced states in terms of demographic and epidemiologic transition. Data from various stakeholders in the field of Gerontology was collected using semi-structured in-depth interviews. A four-step content analysis and themes identification procedure were followed for the data analysis. The study results reiterated the World Health Organisation's (WHO) conceptualisation of healthy ageing, indicating that the intrinsic and extrinsic factors independently or their interacted effect played a potential role in determining healthy ageing. However, the results also revealed that healthy ageing represents only a partial achievement of successful ageing or ageing well. Quality of life (productive/active ageing) and well-being (happiness and freedom) dimensions are inevitable for successful aging. The four overarching themes emerged for preparing a healthy ageing society include (i) planning and resources, (ii) leadership, governance and implementation, (iii) ageing in place, and (iv) opportunities and challenges. The stakeholders perceived that to work towards a healthy ageing society, there is a crucial role for government and non-government partners at various levels.


Medical management of fibroids.
The ideal medical therapy for fibroids is, arguably, a tablet that is taken by mouth, once a day or, even better, once a week, with minimal, if any, side-effects, that induces fibroid regression and thus a resolution of symptoms rapidly, but without affecting fertility. Such a magic bullet does not yet exist, and there are no indications that one is on the horizon. Driven by the observation that fibroid growth is hormone dependent, current medical treatments mainly involve hormonal manipulations. Gonadotrophin-releasing hormone analogues (GnRHa) have been the most widely used, and while they do cause fibroid regression, they can only be used in the short term, as temporizing measures in the perimenopausal woman, or pre-operatively to reduce fibroid size, influence the type of surgery, restore haemoglobin levels and apparently reduce blood loss at operation. They are notorious for rebound growth of the fibroids upon cessation of therapy, and have major side-effects. GnRH antagonists avoid the initial flare effect seen with GnRHa therapy, but otherwise do not appear to have any additional advantages over GnRHa. Selective oestrogen receptor modulators, such as raloxifene, have been shown to induce fibroid regression effectively in post-, but not pre-, menopausal women; even in the former group, experience with these drugs is limited, and they are associated with significant side-effects. Aromatase inhibitors only appear to be effective in postmenopausal women, have potentially significant long-term side-effects, and experience with their use is also limited. There are suggestions that the levonorgestrel intra-uterine system can cause dramatic reduction in menstrual flow in women with fibroids, but to date there have been no RCTs of its use in these women, in whom rates of expulsion of the device appear to be high. The progesterone antagonists mifepristone and asoprisnil have shown significant promise and warrant further research, as they appear to show efficacy in inducing fibroid regression without major side-effects. However, they and the other hormonal therapies that alter oestrogen and progesterone production or function significantly (danazol, gestrinone) are not compatible with reproduction. Therefore, the quest for the ideal medical therapy for fibroid disease continues, and increasing understanding of fibroid biology is ushering in non-hormonal therapies, although all are confined to laboratory experimentation at present. In the meantime, surgical and radiological approaches remain the mainstay effective therapies.


Atrophy of the abdominal wall muscles after extraperitoneal approach to the aorta.
We retrospectively assessed computed tomography (CT) scans to determine degree of anterolateral abdominal muscle atrophy in patients who underwent infrarenal aortic repair with 2 kinds of incisions for the extraperitoneal approach. CT scans obtained before surgery and final scans obtained 2 to 100 months after surgery were assessed in 12 patients with paramedian incision (PM group) and 27 patients with flank incision (F group) who could be followed up at our hospital. We considered muscle thickness before surgery on the incision side to be 100% thickness (baseline value), and we calculated, by measuring the incision side after surgery, the corrected percent thickness (CPT%), which represents percentage of remaining muscle thickness that has escaped incision-induced atrophy. CT scans obtained at the level of the third (L3) and fifth (L5) lumbar vertebrae and the center of the sacrum (S) were selected for CPT% measurement. Duration from surgery to final CT scan was 2 to 65 months (mean +/- SD, 34.33 +/- 21.38 months) in PM group and 3 to 96 months (27.85 +/- 20.74 months) in F group. In PM group, mean CPT% values of the rectus abdominis muscle were 55.83 +/- 21.65% at L3, 35.50 +/- 10.79% at L5, and 31.92 +/- 11.00% at S; these values were statistically much smaller than baseline (P <.01). Mean CPT% values of the lateral abdominal muscles were not statistically different from baseline. In F group, mean CPT% values of the rectus abdominis muscle were 82.19 +/- 23.15% at L5 and 64.41 +/- 31.34% at S; these values were statistically smaller than baseline (P <.01). Mean CPT% values of the lateral abdominal muscles were 87.59 +/- 22.30% at L3 and 84.59 +/- 26.90% at L5; these values were statistically smaller than baseline (P <.05). Paramedian incision induced severe rectus abdominis muscle atrophy. Although flank incision induced various degrees of atrophy in both muscles, some patients had no muscle atrophy. These data indicate that further anatomic investigation into the relation between flank incision and abdominal wall innervation may contribute to prevention of muscle atrophy after flank incision.


Surgical Management of Sarcoma Metastatic to Liver.
Sarcomas are rare mesenchymal tumors with a propensity for hematogenous metastasis. Gastrointestinal stromal tumor (GIST) is the most common histologic subtype and the most common source of hepatic metastases. In the case of metastatic GIST, neoadjuvant imatinib can be used as a selection tool for the judicious application of surgery, where treatment-responsive patients who undergo resection to prevent the development of treatment-resistant clones have associated 10-year actuarial survival of 40%. Further advances for many of the non-GIST sarcoma subtypes will depend on the development of improved systemic therapies and evaluation of their activity in subtype or molecularly defined trials.


WITHDRAWN: Global reverberation and prediction for HRM amid and after COVID-19: A technological viewpoint.
This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been withdrawn as part of the withdrawal of the Proceedings of the International Conference on Emerging Trends in Materials Science, Technology and Engineering (ICMSTE2K21). Subsequent to acceptance of these Proceedings papers by the responsible Guest Editors, Dr S. Sakthivel, Dr S. Karthikeyan and Dr I. A. Palani, several serious concerns arose regarding the integrity and veracity of the conference organisation and peer-review process. After a thorough investigation, the peer-review process was confirmed to fall beneath the high standards expected by Materials Today: Proceedings. The veracity of the conference also remains subject to serious doubt and therefore the entire Proceedings has been withdrawn in order to correct the scholarly record.


PADA-AD Test - a standardized test method for assessing takeover performance of drivers during automated driving.
The presented method describes a standardized test procedure for the evaluation of takeover performance of drivers during automated driving. It was primarily developed to be used for evaluating Level 3 systems (conditional automated driving). It should be applied in a driving simulator environment during the development phase of a system. The method consists of a test course on a three-lane highway with 12 test scenarios where the driver repeatedly has to take over control from the automated system. Each scenario requires the driver to build up an adequate situation awareness in order to take the decision for the correct action. The method was explicitly designed to map the four relevant steps in the takeover process of automated driving: Perception - Awareness - Decision - Action and is therefore called PADA-AD Test for automated driving. The method description contains guidelines with regard to the specification of the test course and the included test scenarios, the design and duration of the automated drives, the non-driving related task to be performed during the automated drives, the instructions to be given to the subjects and finally the measures for evaluating takeover performance of the drivers. • A test procedure for the evaluation of takeover performance of drivers during automated driving was developed for usage in a driving simulator during the development phase of a system/HMI •The test course enables the assessment of the driver's takeover performance in various test scenarios including higher cognitive processes•The method is highly standardized and thus replicable through use of a predetermined test course with clearly defined scenarios, reduced environmental conditions and "popping up" of situational elements.


All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020-22) compared with the pre-pandemic period (2015-19) in South Africa: an observational study.
Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. The Bill & Melinda Gates Foundation.


Effect of CYP3A4 inducer dexamethasone on hepatotoxicity of lapatinib: clinical and in vitro evidence.
Concomitant usage of lapatinib, a cytochrome P450 (CYP) 3A4 substrate and dexamethasone, a CYP3A4 inducer, is a pharmacokinetic drug-drug interaction. This combination may increase the formation of reactive lapatinib metabolites, which is potentially hepatotoxic. This study aims to evaluate the clinical effect of dexamethasone on incidence of hepatotoxicity and to ascertain its in vitro role using a parallel cell culture model experimental setup. Clinical effects of dexamethasone on lapatinib-induced hepatotoxicity were evaluated in a nested case-control study based on 120 patient data obtained from our records. For the in vitro experiment, metabolically competent transforming growth factor α mouse hepatocytes (TAMH) were treated with lapatinib and viabilities were compared in the presence or absence of dexamethasone. After adjusting for confounders, patients receiving the combination were 4.57 times (95% CI 1.23-16.88, p = 0.02) more likely to develop hepatotoxicity and 3.48 times (95% CI 1.24-9.80, p = 0.02) more likely to develop a clinically important change in alanine aminotransferase than compared to the other group. Treatment of TAMH cells with lapatinib and dexamethasone caused a further reduction in viability, as compared to treatment with lapatinib alone. At 5 μM lapatinib, the introduction of dexamethasone 20 μM produced a 59% decline in viability. This is the first study to document a clinically important interaction between lapatinib and dexamethasone, which associates with an increased occurrence of hepatotoxicity. The in vitro findings have provided substantiating evidence and insights on the role of dexamethasone in lapatinib-induced hepatotoxicity.


Correlates of loss to follow-up and missed diagnosis among HIV-exposed infants throughout the breastfeeding period in southern Mozambique.
Complete follow-up of human immunodeficiency virus (HIV)-exposed infants (HEI) is crucial for a successful prevention of mother-to-child HIV transmission. This study analyzed the HEI follow-up and factors associated with loss to follow-up (LTFU) in southern Mozambique. This retrospective cohort study used the data of HEI enrolled between June 2017 and June 2018, followed-up for 18 months. The outcomes were the proportion of infants with completed follow-up and a definitive diagnosis, and the presence of clinical events. Kaplan-Meier survival analysis was used to calculate the cumulative probability of LTFU and of clinical events. Factors associated with LTFU and clinical events were analyzed using Cox regression to calculate the hazard ratio (HR) and adjusted HR (AHR), with a 95% confidence interval (CI) and a significance cutoff of p<0.05. 1413 infants were enrolled (49% males) at a median age of 32 days (IQR 31-41); the median follow-up time was 12 months (IQR 8.2-14.2); 1129 (80%) completed follow-up and had a definitive diagnosis, 58 (4%) were HIV-positive, 225 (16%) were LTFU; 266 (19%) presented a clinical event. Factors associated with LTFU were: age >2 months at entry (AHR, 1.58; 95% CI, 1.12-2.23), non-exclusive breastfeeding (AHR, 1.44; 95% CI, 1.01-2.06), poor cotrimoxazole adherence (AHR, 3.42; 95% CI, 1.59-7.35), and clinical events (AHR, 0.51; 95% CI, 0.34-0.77). Factors associated with clinical events were: malnutrition (AHR, 10.06; 95% CI, 5.92-17.09), non-exclusive breastfeeding (AHR, 1.98; 95% CI, 1.34-2.93), no nevirapine prophylaxis (AHR, 1.67; 95% CI, 1.18-2.36), and poor cotrimoxazole adherence (AHR, 2.62; 95% CI, 1.10-6.22). The high rate of HEI LTFU, associated with delayed linkage to postnatal care, poor prophylaxis adherence, non-exclusive breastfeeding, indicates the need to design a differentiated service delivery model that is tailored to the mothers' and infants' specific needs.


Iron, folate, and vitamin B12 status in the elderly by gender and ethnicity.
National Health and Nutrition Examination Survey 2001-2002 data were used to examine gender and ethnicity relationships to iron, folate, and vitamin B12 status, and anemia in 1770 elderly persons. Dependent variables included dietary intakes and biochemical measures of iron, folate, and vitamin B12 status, and hemoglobin. T Tests were performed using SUDAAN software (version 9.0; Research Triangle Institute International, Research Triangle Park, North Carolina). The relationships of gender and ethnicity to adequacy of iron, folate, and vitamin B12 status, and anemia were investigated using chi2 tests. Males had significantly higher nutrient intakes and better biochemical measures of iron status but lower biochemical measures of folate and vitamin B12. Whites were significantly more likely to have nutrient intakes higher than those recommended by the Food and Nutrition Board. No clear pattern of biochemical measures of iron status was seen among the ethnic groups, and there was no significant relationship between iron status and ethnicity. Biochemical measures of folate status were significantly higher in whites and Mexican Americans than in blacks. No significant relationships were found between folate status and ethnicity. Mean serum vitamin B12 was significantly higher in blacks than in whites and was lowest in other Hispanics who were significantly more likely to be vitamin B12 deficient. Blacks had significantly lower mean hemoglobin values than whites and were significantly more likely to be anemic. Based on biochemical measures, elderly males are at higher risk of folate and vitamin B12 deficiencies. Ethnicity was not significantly related to either iron or folate status. Other Hispanics were significantly more likely to be vitamin B12 deficient.


Pretreatment of rice straw using a butanone or an acetaldehyde dilute solution explosion for producing ethanol.
Ethanol conversion from rice straw using butanone and acetaldehyde dilute solution explosions was evaluated based on the optimization of pure water explosion. To decrease residual inhibitor content, the exploded slurry was dried and investigated at different temperature. Using a 0.9-mol/L butanone solution explosion, with the explosion pressure set at 3.1 MPa, the residence time at 7 min, the dried rice straw-to-water ratio at 1:3 (w/w), and the exploded slurry drying temperuture at 90 °C for 8 h, the yields of total sugar, glucose, and xylose were 85%, 88%, 82% (w/w), respectively, and the ethanol productivity was 26.0 g/100 g rice straw dry matter. Moreover, 0.5-mol/L acetaldehyde dilute solution explosion improved the efficiency of enzymatic hydrolysis (EH) and simultaneous saccharification and co-fermentation (SSCF), and the residual inhibitors had negligible effects on EH and SSCF after detoxification by drying. The results suggested that compared with pure water explosions, the use of butanone and of acetaldehyde dilute solution explosions lowered the explosive temperature and improved the sugar yield, although relative crystallinity of the rice straw dry matter was increased after the explosion.


Long-term clinical outcomes and cause of death after endovascular treatment for femoropopliteal artery lesions.
Endovascular treatment (EVT) for femoropopliteal artery disease is common in clinical practice. However, little is known about its prognostic factors, causes of death, and long-term clinical outcomes. Two hundred eighty-five consecutive patients (mean age, 72±8 years, 73% men) undergoing their first EVT for de-novo femoropopliteal artery disease from 2009 to 2018 were studied. Patients were divided in two groups according to the presence of critical limb ischemia (CLI). We evaluated the incidence of major adverse limb events (MALE) including clinically driven target vessel revascularization and target limb major amputation, and all-cause death. The procedure was successful in 97.9% of cases. The non-CLI group comprised 205 patients (72%), and the CLI group comprised 80 patients (28%). The CLI group exhibited higher high-sensitivity C-reactive protein (hs-CRP) levels and a higher rate of hemodialysis than the non-CLI group. During the median follow-up period of 3.5 years, there were 62 deaths (21.8%) including cardiovascular (32.3%), infection (32,3%), and malignancy-related (22.6%) deaths. Kaplan-Meier analysis revealed that the CLI group had a significantly higher incidence of MALE and all-cause death (log-rank, both p<0.001, respectively). The leading causes of death in the CLI group were cardiovascular- and infection-related death; the leading cause of death in the non-CLI group was malignancy-related. On multivariate Cox hazard analysis, hemodialysis, TASC II classification C/D lesions, and CLI were significant predictors of MALE (p<0.001, p=0.005, and p=0.012, respectively). Hemodialysis, age, higher hs-CRP levels, and CLI were significant predictors of all-cause death (p<0.001, p=0.003, p=0.009, and p=0.021, respectively). Although EVT for femoropopliteal artery disease appears feasible with a high rate of procedural success, a high incidence of MALE and all-cause death was observed. Further studies are needed to improve the outcomes in patients with CLI.


A meta-analytic review of prospection deficits in Parkinson's disease.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and is associated with prominent motor deficits. However, neurocognitive impairment is also a common clinical feature that can contribute greatly to the overall disease burden. In the current study, a meta-analysis was conducted to gain a clearer understanding of how PD affects one of the most functionally important domains of cognition: prospection. The results indicate that, relative to controls, PD is associated with a large deficit in the capacity to engage in planning (g = -0.81, K = 25) and a moderate-sized deficit in prospective memory (g = -0.57, K = 16). Sub-analyses indicated that these deficits are evident for both time and event-based prospective memory, as well as for prospective memory tasks that have relatively limited ecological validity. Significant impairment was also evident for both medicated and non-medicated PD sub-groups, but for planning, these deficits were substantially greater in the unmedicated sub-group. The theoretical and practical implications of these findings are discussed.


Spatial stimuli in films: Uncovering the relationship between cognitive emotion and perceived environmental quality.
The research paper establishes the impact of spatial stimulus on human cognition and emotion by studying environmental events as cues to understand how people perceive spatial qualities. The medium of film to implement visually disruptive events was used in the research to find the relationship between the subjective evaluation of space and emotional responses. Ninety participants participated in watching three films showcasing unexpected spatial stimuli, thus impacting their psychological state. Standard questionnaires involving Aesthetic chills and The Self-Assessment Manikin (SAM) model were used to capture emotional responses, and Normalized Accumulated Quality (NAQ) model was used to receive space quality assessments. The Pearson correlation coefficient was subsequently used to find the association of chills and The SAM with NAQ. Univariate and multivariate regression models were also conducted to find the impact of emotional responses on NAQ. A significant association of NAQ with chills (p-value: 0.001), pleasure (p-value <0.001), arousal (p-value: 0.016), and dominance (p-value: 0.015) was witnessed in film 1. In film 2, NAQ was significantly associated with pleasure (p-value <0.001), while in film 3, NAQ was highly associated with arousal (p-value: 0.043). According to the adjusted impact of variables on NAQ in film 1, significant impacts of chills (p-value: 0.028), arousal (p-value: 0.117), pleasure (p-value <0.001), and dominance (p-value: 0.113) on NAQ were observed. In film 2, pleasure (p-value <0.001) and dominance (p-value: 0.113) impacted NAQ using the univariate model, while only pleasure had an impact on NAQ in the multivariate model. In film 3, arousal was the only variable to impact NAQ (p-value: 0.043) in a univariate model. In regression analyses, higher slopes were witnessed for models in film 1. The experiment highlighted that using affect-based video clips can help us capture the relationship between emotional responses and perceived quality of space. The appearance of spatial stimuli can engage learning, expectation, and attention, leading to a superior improvement of cognitive ability and mental health in space. This level of understanding can help design a more sustainable place.


Phosphatidylethanol counteracts calcium-induced membrane fusion but promotes proton-induced fusion.
The susceptibility of phosphatidylethanol-containing lipid vesicles towards Ca2+- and proton-induced fusion has been investigated, using a system of interacting vesicles. The results show that phosphatidylethanol-rich vesicles are quite resistant to Ca2+-induced fusion while being highly sensitive to proton-induced fusion. Inclusion of phosphatidylethanol was also found to promote and inhibit, respectively, the proton-induced and Ca2+-induced fusion of bilayer vesicles containing also phosphatidylethanolamine and either phosphatidylserine or phosphatidic acid. Thus, phosphatidylethanol affected Ca2+- and proton-induced fusion in opposite directions, in contrast to the naturally occurring anionic phospholipids phosphatidic acid, phosphatidylserine and phosphatidylinositol, which affect the sensitivity to Ca2+- and H+-induced fusion in the same direction. However, the fusion competence of phosphatidylethanol vesicles in response to both Ca2+ and H+ was inversely related to the apparent thickness of the polar headgroup layer, determined by using lectin-glycolipid interaction as a steric probe, as previously found for vesicles containing naturally occurring anionic phospholipids.


Inborn errors of TLR3- or MDA5-dependent type I IFN immunity in children with enterovirus rhombencephalitis.
Enterovirus (EV) infection rarely results in life-threatening infection of the central nervous system. We report two unrelated children with EV30 and EV71 rhombencephalitis. One patient carries compound heterozygous TLR3 variants (loss-of-function F322fs2* and hypomorphic D280N), and the other is homozygous for an IFIH1 variant (loss-of-function c.1641+1G>C). Their fibroblasts respond poorly to extracellular (TLR3) or intracellular (MDA5) poly(I:C) stimulation. The baseline (TLR3) and EV-responsive (MDA5) levels of IFN-β in the patients' fibroblasts are low. EV growth is enhanced at early and late time points of infection in TLR3- and MDA5-deficient fibroblasts, respectively. Treatment with exogenous IFN-α2b before infection renders both cell lines resistant to EV30 and EV71, whereas post-infection treatment with IFN-α2b rescues viral susceptibility fully only in MDA5-deficient fibroblasts. Finally, the poly(I:C) and viral phenotypes of fibroblasts are rescued by the expression of WT TLR3 or MDA5. Human TLR3 and MDA5 are critical for cell-intrinsic immunity to EV, via the control of baseline and virus-induced type I IFN production, respectively.


Effects of the subterranean herbivorous rodent Spalacopus cyanus on herbaceous vegetation in arid coastal Chile.
The impact of the subterranean herbivorous rodent Spalacopus cyanus Molina on the herbaceous vegetation was studied by comparing biomass, species richness and species diversity at the end of the growing season in areas with and without burrows in coastal arid Chile. Total biomass was 60% higher in areas with burrows. This difference was mainly due to the large increase of Mesembryanthemum cristallinum L., a succulent prostrate annual herb. Unexpectedly, bulb biomass of geophytes, eaten by Spalacopus, did not differ between areas. However, in areas with burrows bulbs of geophytes were more numerous and smaller. It is possible that burrowing activities facilitate the occurrence of new small bulbs through seed germination. Species composition and diversity did not differ greatly between areas. Burrowing activities by Spalacopus, the life cycle of Mesembryanthemum, and climate seem to be the most important factors determining species abundance and diversity of herbs in this system.


Association between intracranial aneurysm and meningiomas: An integrative survival Analysis with identification of prognostic factors.
To analyze prognostic factors in clinical association between intracranial aneurysm (IA) and meningioma. Prognostic factors on overall survival (OS) were evaluated. We selected articles, published from January 1944 to December 2018 on the Medical databases (Web of Sciences, Medline and EMBASE) and included case series and reports. Clinical information was obtained and variables associated with the primary outcome of 27-mo survival were identified through Cox regression models. The study evaluated 77 patients. Female represented 76.6 % (n = 59), a ratio of 3.27 female: 1 male. The age range was 7-84 years old, with an average of 54.74 (SD: 14.30). Age and sex were not significant statistically different between the two groups for overall survival (OS) (log-rank P = 0.806), (log-rank P = 0.983) respectively. 77.9 % (n = 60) were ipsilateral, the same side was 4 times more common in univariate analysis (P = 0.052; 95 % CI, 0.924-17.319). Most aneurysms were detected in the internal carotid artery, 29.87 %. In Clinical data, 62.33 % (n = 48) had exclusive tumor symptoms, while 25.97 % (n = 20) presented exclusively subarachnoid hemorrhage (SAH). In multivariate analysis, although there is an independent protective factor for those who did not have SAH (HR; 0.099; CI; 0.010-0.986; P = 0.049) and the treatment is an independent predictor for OS (HR, 42.096; CI, 4.270-415.056; P = 0.01). This is the first study to approach this association. This is not just an occasional finding, but it seems to have a shared pathophysiology. Unruptured aneurysms and treatment modality were protective independent factors for OS. Prospective studies are warranted to provide definitive answers.


A case of post-transplant hyperparathyroidism treated with ethanol injection.
A 15-year-old boy with chronic renal failure secondary to Alport's syndrome underwent living-related renal transplantation from his 48-year-old father. His primary immunosuppressive regimen was composed of tacrolimus, mizolibine, and methylprednisolone. The postoperative course was satisfactory with one episode of mild acute rejection, treated successfully with methylprednisolone pulse therapy. Two months later, hypercalcemia (11.8-13.2 mg/dl) and hypophosphatemia (2.5-3.0 mg/dl) were noted without any bone symptoms. The serum intact-parathyroid hormone (PTH) and serum alkaline phosphatase levels were 240 pg/ml and 2483 IU/l, respectively. Ultrasound studies revealed enlargement of the two parathyroid glands. Under the diagnosis of tertiary hyperparathyroidism, he underwent percutaneous ethanol injection (PEIT) into the left parathyroid gland. Although levels of serum calcium and phosphorus returned to normal ranges and the intact PTH level decreased to 95 pg/ml with the three injections, another injection was needed to normalize recurrent hypercalcemia 2 months later. The patient experienced only transient mild dysphonia and local pain after PEIT. Although PEIT is believed less effective than parathyroidectomy, it has some advantages such as applicability to high-risk patients, repeatability of treatment, low incidence and severity of side effects.


Foliar 15N natural abundance in Hawaiian rainforest: patterns and possible mechanisms.
Foliar samples were obtained from symbiotic nitrogen-fixers and control plants (non-fixers) along elevational and primary successional gradients in volcanic sites in Hawai'i. Most control plants had negative δ15N values (range-10.1 to +0.7‰), while most nitrogen-fixers were near 0‰. Foliar 15N in the native tree Metrosideros polymorpha did not vary with elevation (from sea level to tree-line), but it did increase substantially towards 0‰ on older soils. The soil in an 197-yr-old site had a δ15N value of approximately-2‰, while in a ∼67000-yr-old site it was +3.6‰. We suggest that inputs of 15N-depleted nitrogen from precipitation coupled with very low nitrogen outputs cause the strongly negative δ15N values in non-nitrogen-fixing plants on early successional sites.


Considerations on self-psychology and eating disorders.
In this narrative review article, some considerations are reported on the psychoanalytic point of view of self-psychology on eating disorders in a multidisciplinary team approach, a theoretic and clinical perspective in which the Author recognizes himself. Some author's clinical ideas and concepts as "negative self", "eclipse of the self", "rebound syndrome", "bluff syndrome", "deficit of subjective attribution", related to the topic of the deficit of the Self, are exposed along with technical aspects, clinical material and references to the comparison of psychoanalysis with the EBM literature on psychotherapy of EDs and its contemporary role in an integrated multi-disciplinary treatment of these disorders.


Transmissibility of infectious bronchitis virus H120 vaccine strain among broilers under experimental conditions.
The aim of this study was to quantify transmission of infectious bronchitis virus (IBV) H120 vaccine strain among broilers, and to assess whether birds that have been exposed to vaccine strain-shedding birds were protected against clinical signs after infection with a virulent strain of the same serotype. A transmission experiment and a replicate were carried out, each with six groups of commercial broilers. At day of hatch (n = 30) or at 15 days of age (n = 20), half of each group was inoculated with either IBV H120 vaccine (H120 group), virulent IBV M41 (M41 group), or were mock-infected, thereby contact-exposing the other half of each group. Nasal discharge was recorded, and antibody response and virus shedding were measured. To measure clinical protection, four weeks after inoculation all birds, in all groups, were challenged with IBV M41. The reproduction ratio (R; the average number of contact infections caused by one infectious bird) was determined to quantify virus transmission. All contact-exposed birds, except for one in an H120 group, became infected with either IBV H120 or IBV M41. Almost all birds contact-infected with IBV H120 or IBV M41 were subsequently protected against clinical signs after challenge with IBV M41. The lower limits of the 95% confidence interval (CI) of the R of IBV H120 vaccine, and of IBV M41, were significantly <1. For both IBV H120 and IBV M41, the 95% CI was [2.1-infinity] following inoculation at day of hatch and [1.8-infinity] after inoculation at 15 days of age. This finding demonstrates that IBV H120 vaccine is able to spread extensively among broilers. This implies that this vaccine strain might be able to become endemically present in the poultry population. It also implies that, even if not all birds received vaccine during spray application, due to the ability of the vaccine to spread in the flock, they will most likely be protected against clinical signs after a subsequent field virus infection.


Dosage of hemoglobin A1c by isoelectrofocusing.
A new Hb A1c routine dosage method is proposed, using thin-layer isoelectrofocusing. The mean level in normal adults is 4.66% (sigma = 1.05). In diabetic (treated) patients, the distribution of Hb A1c levels is a non-Gaussian one, with extreme values of 3 to 13% and a maximum frequency peak at 5.5%.


Synthesis, antitumor activity and SAR study of novel [1,2,4]triazino[4,5-a]benzimidazole derivatives.
A series of novel 1,2,3,4-tetrahydro[1,2,4]triazino[4,5-a]benzimidazoles carrying variety of aryl and heteroaryl groups at position 1 were synthesized. The newly synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7). Some of the test compounds showed potent antitumor activity, especially compound 3c [1-(2-chlorophenyl) derivative] which displayed the highest activity among the test compounds.


Scaffold hybridization in generation of indenoindolones as anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase.
Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to etoposide and 5-fluorouracil in kidney cancer cells (HEK 293) and low toxicity to corresponding normal cells (Vero). They exerted apoptotic effect with blocking of cell cycle at G2/M phase.


Dipivalyl epinephrine: a new pro-drug in the treatment of glaucoma.
The dansyl chloride technique in conjunction with thin layer chromatography and autoradiography has shown that dipivalyl epinephrine is a pro-drug in the human eye. Dipivalyl epinephrine appears to be a more effective epinephrine compound, in that it penetrates the cornea approximately 17 times greater than epinephrine.


Zero-contrast PTRA and stenting for child with TRAS: A case report.
Kidney transplantation is often complicated by TRAS, and PTRA can effectively treat it. However, PTRA is not appropriate for patients with CKD because iodinated contrast agent may induce nephropathy. This article reports about a 14-year-old boy with a history of kidney transplantation complicated by RAS. He initially underwent percutaneous balloon dilation to relieve the stenosis. One and half a year after dilation, he received zero-contrast PTRA and stenting under the guidance of external and IVUS with reference to previous PAG image. After successful stent implantation, the cross-sectional area of the renal artery lumen was significantly increased.The blood pressure and level of creatinine also decreased and kept stable during follow-up. This report suggests the feasibility of external ultrasound and IVUS guided, zero-contrast PTRA in patients with poor renal function or iodinated contrast allergy.


Trends in life expectancy with care needs based on long-term care insurance data in Japan.
Using a previously developed method for calculating expected years of life with care needs based on data from the Japanese long-term care insurance system, we examined recent trends in expected years of life with care needs by age group and prefecture. Information on care needs was available from the long-term care insurance system of Japan. Expected years of life with care needs by age group and prefecture in 2005-2009 were calculated. Expected years of life with care needs at age 65 increased from 1.43 years in 2005 to 1.62 years in 2009 for men, and from 2.99 to 3.44 years for women. As a proportion of total life expectancy, these values show an increase from 7.9% to 8.6% in men and from 12.9% to 14.4% in women. Expected years with care needs did not increase in the age groups of 65 to 69 and 70 to 74 years but markedly increased in the age group of 85 years or older. Expected years with care needs increased in every prefecture during the period studied. The difference in 2005 between the 25th and 75th percentiles in prefectural distributions was 0.16 years for men and 0.35 years for women. The difference remained nearly constant between 2005 and 2009. Expected number of years of life with care needs increased among Japanese from 2005 to 2009, and there was a wide range in distribution among prefectures. Further studies on coverage of care needs under the long-term insurance program are necessary.


Optimizing JC and BK polyomavirus IgG testing for seroepidemiology and patient counseling.
Polyomavirus JC (JCPyV) and BK (BKPyV) can cause significant diseases in immunocompromised patients including nephropathy, hemorrhagic cystitis, and leukoencephalopathy. Recently, JCPyV and BKPyV IgG have been explored as risk predictors in multiple sclerosis and transplant patients, but sensitivity, specificity and quantification issues limit current performance. To improve JCPyV and BKPyV-specific antibody testing. Healthy blood donor sera (N=400) were tested at dilutions 1:100, 1:200, and 1:400 for JCPyV- and BKPyV-specific IgG using VP1 virus-like particle (VLP)-based ELISAs normalized to a laboratory reference serum. Normalized optical density 492nm greater or equal 0.1 in all 3 dilutions was regarded as reactive. Sera with discordant reactivity in at least one dilution were retested after VLP preadsorption. At dilutions 1:100, 1:200, and 1:400, IgG reactivity was 74%, 60% and 53% for JCPyV, and 93%, 86% and 74% for BKPyV, respectively. At these dilutions, JCPyV-VLP preadsorption identified 56, 4 and 0 false-positives and 0, 4 and 27 false-negatives, respectively. Dilution-dependent sensitivity was 100%, 98%, and 89%, and specificity 65, 98%, and 100%, respectively. For sera diluted 100-, 200-, and 400-fold, BKPyV-VLP preadsorption identified 28, 1 and 0 false-positives, and 0, 0 and 46 false-negatives, and sensitivity was 100%, 100%, 86%, and specificity 50%, 98%, 100%, respectively. For seroepidemiology studies, normalized JCPyV and BKPyV IgG ELISA at 1:200 serum dilution provides optimal sensitivity and specificity with the lowest false-positive and false-negative rate. For individual risk assessment, dilutions of 100, 200, and 400 combined with preadsorption for low-reactive sera may be most appropriate.


Varying Mutational Alterations in Multiple Primary Melanomas.
In melanoma, the mitogen-activated protein (MAP) kinase pathway plays a crucial oncogenic role. Recent studies identified additional genetic alterations, eg, TERT-promoter mutations. Up to 8% of melanoma patients present with multiple primary melanomas (MPMs). The pathogenesis is not fully understood, and data on the genetic diversity of MPMs are limited. To identify putative diagnostic and therapeutic consequences, we assessed the mutational status of the BRAF and NRAS genes and TERT promoter in patients with MPMs. The study cohort consisted of 96 patients with 237 malignant melanomas. The BRAF, NRAS, and TERT-promoter genotypes were assessed in all MPMs and were correlated with patients' clinicopathological characteristics. BRAF mutations were found in 84 melanomas (35.4%), NRAS mutations, in 33 (14.0%); and TERT-promoter mutations, in 112 (47.3%). Mutation patterns were concordant between first and subsequent primary tumors in 23.9% of patients and were discordant in 61.4% of patients. The genetic alterations were partially different in 14.7% of patients. By Cox regression analysis, only the NRAS mutation had a significant negative prognostic impact on time to progression to stage III (P = 0.016) and on distant metastasis-free survival (P = 0.032). In the majority of primary melanomas in patients with MPMs, BRAF, NRAS, and TERT-promoter genotypes were discordant. Thus, molecular testing for targeted therapy should be performed on metastatic tissue and not on primary tumors.


The biological rationale and clinical efficacy of inhibition of signaling kinases in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is still incurable, with considerable resistance to the standard therapy. CLL cells receive anti-apoptotic and pro-proliferation stimuli in lymph nodes and bone marrow, mainly through B cell receptor activation and TNF-receptor family ligation. In recent years, the focus for finding new drugs has shifted to blocking signals from the microenvironment. Novel therapeutical agents interfere with these microenvironmental interactions, and include inhibitors of kinases Syk, Btk and PI3Kδ. In this review we will focus on the microenvironmental interactions of CLL and the role of tyrosine kinases. Furthermore, early results from clinical trials with kinase inhibitors are discussed.


Controllable incorporation of 1,2,4-triazolate into cluster-based metal-chalcogenide frameworks.
The first incorporation of the 1,2,4-triazolate ligand into metal-chalcogenide semiconductor frameworks resulted in the formation of two new supertetrahedral-cluster-based triazolate frameworks (SCTFs) with hybrid inter-cluster connection modes, namely, SCTF-1 with an inorganic/organic linker ratio of 3 : 1 and SCTF-2 with a linker ratio of 2 : 2. The optical properties of these two close models were investigated.


Antidepressant-like effects of solidagenone on mice with bacterial lipopolysaccharide (LPS)-induced depression.
Considering the pharmacological potential of solidagenone from Solidago chilensis, the present investigation was carried out to evaluate its antidepressant-like effect in mice with bacterial lipopolysaccharide (LPS)-induced depressive like behavior and its mode of action through the measurement of neuroinflammatory and oxidative markers. In the prophylactic test, the mice were pretreated with solidagenone (1, 10 or 100 mg/kg, p.o) and after one hour received LPS. In therapeutic test, the mice received LPS and after 5 h were treated with solidagenone (1, 10 or 100 mg/kg, p.o). In both experimental approaches, the animals were submitted to OFT and to the TST after 6 and 24 h of the LPS administration, respectively. One hour after the TST the animals were euthanized, the blood was collected, the cortex was removed and biochemical analyzes were performed for measurement of the inflammatory and oxidative stress markers. The LPS induced sickness- and depressive-like behaviors and increased the cortical activity of myeloperoxidase (MPO), as well as the IL-6 and TNF amount. Interestingly, the pretreatment with solidagenone at 100 mg/kg avoided the behavioral alterations in OFT. In the mice post treated with solidagenone, all tested doses of resulted in an antidepressant-like effect evidenced by the decrease in immobility time in the TST. This effect was accompanied by a decrease in the MPO activity and in the IL-6 and TNF levels in the cortex in parallel to the increase in catalase activity. The solidagenone has a promissor antidepressant-like potential, which can result of its beneficial action in the neuroinflammation process and due its antioxidant capability at the central nervous system.


Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS.
In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called "distorted key" approach) was also briefly elucidated.


Executive impairment is associated with unawareness of neuropsychiatric symptoms in premanifest and early Huntington's disease.
Unawareness of neuropsychiatric symptoms appears to be common in Huntington's disease (HD), but the clinical correlates of unawareness are unclear. Identifying predictors of unawareness is important for improving diagnosis of neuropsychiatric symptoms, and cognitive impairment, specifically executive impairment, may be a potential important predictor of unawareness. The authors examined whether unawareness of neuropsychiatric symptoms is more common in early HD compared to premanifest HD, and whether executive task performance was associated with awareness, independent of demographic, motor or mood variables. One hundred thirty-two gene-positive participants (60 premanifest and 72 early diagnosed) from the multicenter TRACK-HD study were included. Participants and their informants completed self and informant versions of the Frontal Systems Behavior Scale, which measures executive dysfunction, apathy, and disinhibition symptoms. Awareness was measured as the discrepancy between self- and informant-reports across premanifest and early HD groups. Participants' executive task performance was then assessed as a predictor of unawareness across the whole group. Premanifest participants reported higher levels of executive dysfunction, apathy and disinhibition than their informants, whereas early HD participants reported less executive dysfunction and apathy than their informants, indicating that unawareness is more common after diagnosis. Impaired executive task performance was related to unawareness of executive dysfunction and apathy, independent of demographic, motor and mood variables. Executive impairment is a useful early predictor of unawareness of neuropsychiatric symptoms in HD. Clinicians should closely monitor HD patients with executive impairment for unawareness, and consider this when assessing neuropsychiatric symptoms in HD and providing education to patients and families. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Can diet combined with treatment scheduling achieve consistency of rectal filling in patients receiving radiotherapy to the prostate?
This pilot study investigates whether an individualized fluid and fibre prescription combined with a constant treatment can improve rectal filling consistency during radiotherapy. Fibre, fluid intake and bowel function were assessed in 22 patients at a standard planning scan (SCT) and individualized dietary advice was prescribed to regularize bowel habit. Patients were requested to record frequency and type of bowel movements, fibre and fluid intake daily. Two subsequent CT scans were acquired at 7 (CCT1) and 10 days (CCT2) after SCT at a similar time. Rectal volume and gas were measured planning CT's and 'on treatment' cone beam CT scans. We hypothesised that the difference in volume between CCT1 and CCT2 would be less than the difference between SCT and CCT1. The mean (SD) change in volume between SCT to CCT1 and CCT1 to CCT2 was 5.68 cm(3) (26.2) and -8.6 cm(3) (40.1), respectively (p=0.292). Of the 22 patients scanned 20 provided a complete record of dietary intake and bowel motion. The majority of patients either achieved or exceeded prescription. Change in rectal gas was the only correlation with change in rectal volume. Patient self reporting of bowel motion, fibre, fluid intake was achievable but consistency of rectal filling was not improved. Improved understanding of the aetiology and management of rectal gas is indicated.


Glutathione regulates caspase-dependent ceramide production and curcumin-induced apoptosis in human leukemic cells.
Depletion of intracellular glutathione (GSH) is the prime hallmark of the progression of apoptosis. Previously, we reported that curcumin induces reactive oxygen species (ROS)-mediated depletion of GSH, which leads to caspase-dependent and independent apoptosis in mouse fibroblast cells (F. Thayyullathil et al., Free Radic. Biol. Med.45, 1403-1412, 2008). In this study, we investigated the antileukemic potential of curcumin in vitro, and we further examined the molecular mechanisms of curcumin-induced apoptosis in human leukemic cells. Curcumin suppresses the growth of human leukemic cells via ROS-independent GSH depletion, which leads to caspase activation, inhibition of sphingomyelin synthase (SMS) activity, and induction of ceramide (Cer) generation. Pretreatment of leukemic cells with carbobenzoxy-Val-Ala-Asp fluoromethylketone, a universal inhibitor of caspases, abrogates the SMS inhibition and Cer generation, and in turn prevents curcumin-induced cell death. Curcumin treatment of leukemic cells also downregulates the expression of the inhibitor of apoptosis proteins (IAPs), phospho-Akt, c-Myc, and cyclin D1. Extracellular supplementation with GSH attenuates curcumin-induced depletion of GSH, caspase-dependent inhibition of SMS, Cer generation, and downregulation of IAPs, whereas, L-D-buthionine sulfoximine, a widely used inhibitor of GSH synthesis, potentiates GSH depletion, Cer generation, and apoptosis induced by curcumin. Taken together, our findings provide evidence suggesting for the first time that GSH regulates caspase-dependent inhibition of SMS activity, Cer generation, and apoptosis induced by curcumin in human leukemic cells.


Extent of early ischemic changes on computed tomography (CT) before thrombolysis: prognostic value of the Alberta Stroke Program Early CT Score in ECASS II.
The significance of early ischemic changes (EICs) on computed tomography (CT) to triage patients for thrombolysis has been controversial. The Alberta Stroke Program Early CT Score (ASPECTS) semiquantitatively assesses EICs within the middle cerebral artery territory using a10-point grading system. We hypothesized that dichotomized ASPECTS predicts response to intravenous thrombolysis and incidence of secondary hemorrhage within 6 hours of stroke onset. Data from the European-Australian Acute Stroke Study (ECASS) II study were used in which 800 patients were randomized to recombinant tissue plasminogen activator (rt-PA) or placebo within 6 hours of symptom onset. We retrospectively assessed all baseline CT scans, dichotomized ASPECTS at < or =7 and >7, defined favorable outcome as modified Rankin Scale score 0 to 2 after 90 days, and secondary hemorrhage as parenchymal hematoma 1 (PH1) or PH2. We performed a multivariable logistic regression analysis and assessed for an interaction between rt-PA treatment and baseline ASPECTS score. We scored ASPECTS >7 in 557 and < or =7 in 231 patients. There was no treatment-by-ASPECTS interaction with dichotomized ASPECTS (P=0.3). This also applied for the 0- to 3-hour and 3- to 6-hour cohorts. However, a treatment-by-ASPECTS effect modification was seen in predicting PH (0.043 for the interaction term), indicating a much higher likelihood of thrombolytic-related parenchymal hemorrhage in those with ASPECTS < or =7. In ECASS II, the effect of rt-PA on functional outcome is not influenced by baseline ASPECTS. Patients with low ASPECTS have a substantially increased risk of thrombolytic-related PH.


Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial.
In addition to its anti-ischaemic effects, the antianginal drug nicorandil is thought to have cardioprotective properties. We did a randomised trial to find out whether nicorandil could reduce the frequency of coronary events in men and women with stable angina and additional risk factors. 5126 patients were randomly assigned 20 mg nicorandil twice daily (n=2565) or identical placebo (n=2561) in addition to standard antianginal therapy. The primary composite endpoint was coronary heart disease death, non-fatal myocardial infarction, or unplanned hospital admission for cardiac chest pain. The secondary endpoint was the combined outcome of coronary heart disease death or non-fatal myocardial infarction. Other outcomes reported include all-cause mortality, all cardiovascular events, and acute coronary syndromes. Mean follow-up was 1.6 years (SD 0.5). Analysis was by intention to treat. There were 398 (15.5%) primary endpoint events in the placebo group and 337 (13.1%) in the nicorandil group (hazard ratio 0.83, 95% CI 0.72-0.97; p=0.014). The frequency of the secondary endpoint was not significantly different between the groups (134 events [5.2%] vs 107 events [4.2%]; 0.79, 0.61-1.02; p=0.068). The rate of acute coronary syndromes was 195 (7.6%) in the placebo group and 156 (6.1%) in the nicorandil group (0.79, 0.64-0.98; p=0.028), and the corresponding rates for all cardiovascular events were 436 (17.0%) and 378 (14.7%; 0.86, 0.75-0.98; p=0.027). We showed a significant improvement in outcome due to a reduction in major coronary events by antianginal therapy with nicorandil in patients with stable angina.


T-cryptantigen (TCA) activation in surgical neonates: a hidden problem.
The Thomsen-Friedenreich cryptantigen (TCA) is located on the surface of all red cells, but is concealed by a layer of neuraminic acid. When bacteria that produce neuraminidase disrupt this coating, the TCA can be exposed and activated. If blood products containing antibody to the TCA are subsequently administered, haemolysis can result. While the relationship between TCA and necrotising enterocolitis (NEC) is well described, the incidence of TCA activation in other forms of sepsis in surgical neonates is not known. In a prospective study, 117 patients admitted to the Surgical Neonatal Nursery were examined for evidence of TCA activation. Of the 117 babies, 69 were clinically non-septic and only 1 had weak TCA activation (1.4%). Forty-eight were clinically or bacteriologically septic; 8 of these demonstrated TCA activation (17%), 3 of whom died. Forty of the septic group showed no evidence of TCA activation although 27 grew organisms on culture; 17 in this group died. Two of the TCA-activated babies received unwashed red cells, and both haemolysed; 4 TCA-activated babies received washed red cells and none haemolysed. Although 1 of the well babies in this study demonstrated TCA activation, we would not recommend routine TCA testing on clinically well babies. We would, however, recommend routine testing in all clinically septic infants, as 17% showed signs of TCA activation in this study. We would also suggest the adoption of a selective transfusion policy in TCA-activated patients to avoid the risk of haemolysis. This may help to reduce unnecessary morbidity and mortality in a high-risk group of neonates.


Immunological cross-reactivity between preS2 sequences of the hepatitis B virus envelope proteins corresponding to serological subtypes adw2 and ayw.
An immune response to epitopes localized on the preS region of the hepatitis B virus (HBV) envelope (env) is elicited during recovery from HBV infection and appears to play a role in virus clearance. Anti-preS antibodies (Ab) are expected to be protective against HBV infection as indicated by the virus-neutralizing capacity of Ab to a preS2-specific synthetic peptide preS(120-145). However, there is considerable amino acid variability between preS regions corresponding to distinct serological subtypes of HBV, raising the question whether the preS sequences are sufficiently related immunologically to have the potential of inducing cross-protective immunity. To answer this question concerning the preS2 region, antisera to synthetic peptides preS(120-153) and preS(128-153) corresponding to subtypes adw2 and ayw, as well as to the native env [ayw] protein were raised. Using the resulting polyclonal Ab, an immunological relatedness between preS2 sequences of subtypes adw2 and ayw was demonstrated. On the other hand, Ab selected by affinity chromatography or by cloning hybridoma cells may recognize with strong preference subtype-specific determinants within the preS2 region when the compared antigens are in solution rather than on the solid phase. These findings have implication for the design of: (1) preS2-specific immunogens and (2) immunoassays for quantitation of preS2 sequences in HBV env proteins.


Melanoma arising de novo over a 16-month period.
Choroidal melanoma is widely regarded as a slow-growing tumor. We report herein the first documented case, to our knowledge, of a choroidal melanoma present in an eye in which examination 16 months earlier disclosed no tumor. On gross examination following enucleation, the largest tumor diameter at the base was 19 mm and the height was 11 mm. The implications as to the growth rate and the precursor lesions of choroidal melanomas are discussed.


Selection of stable reference genes in heat stressed peripheral blood mononuclear cells of tropically adapted Indian cattle and buffaloes.
Eleven reference genes from different functional categories were assessed for their stable expression pattern in heat stressed PBMCs across Indian buffalo and cattle using GeNorm, NormFinder and BestKeeper algorithms. As the first report, we suggest B2M, RPS9 and RPS15a as suitable reference genes for accurate normalization of PBMC transcript data while the ACTB gene is not recommended.


Hexavalent chromium damages chamomile plants by alteration of antioxidants and its uptake is prevented by calcium.
Toxicity of low (3μM) and high (60 and 120μM) concentrations of hexavalent chromium/Cr(VI) in chamomile plants was studied. Fluorescence staining confirmed reduction of Cr(VI) to Cr(III). Cr was mainly accumulated in the roots with translocation factor <0.007. Notwithstanding this, both shoots and roots revealed increase in oxidative stress and depletion of glutathione, total thiols, ascorbic acid and activities of glutathione reductase and partially ascorbate peroxidase mainly at 120μM Cr. Though some protective mechanisms were detected (elevation of nitric oxide, enhancement of GPX activity and increase in phenols and lignin), this was not sufficient to counteract the oxidative damage. Consequently, soluble proteins, tissue water content and biomass production were considerably depleted. Surprising increase in some mineral nutrients in roots (Ca, Fe, Zn and Cu) was also detected. Subsequent experiment confirmed that exogenous calcium suppressed oxidative symptoms and Cr uptake but growth of chamomile seedlings was not improved. Alteration of naturally present reductants could be a reason for Cr(III) signal detected using specific fluorescence reagent: in vitro assay confirmed disappearance of ascorbic acid in equimolar mixture with dichromate (>96% at pH 4 and 7) while such response of glutathione was substantially less visible.


The visualization of femoral vessels in delayed bone scans--a sign of arteriosclerosis? A comparison of 99mTc-MDP and 99mTc-DPD.
The activity of femoral vessels in delayed bone scans was evaluated visually in 237 consecutive patients and quantified in 40 female patients. In visual analysis the patients were randomly divided into three groups and in quantitative analysis into four groups of equal size. Two different MDP preparations and one DPD preparation were used as bone-seeking agents. With aging, the activity in femoral vessels increased with all agents in visual analysis, significantly with MDPs (P less than 0.001) between patients less than or equal to 60 years and greater than 60 years. In female patients with all agents a significant increase in femoral activity was found (P less than 0.001 with MDPs, P less than 0.05 with DPD). In patients greater than 60 years, the femoral uptake was significantly higher with MDP when compared with the DPD uptake (P less than 0.01 with MDP1, P less than 0.05 with MDP2). Between the MDPs no significant differences were found. In quantitative analysis the femoral vessel to soft tissue ratio was significantly higher in patients greater than 70 years when compared with patients less than or equal to 50 years with MDP. No difference was found with DPD. Histological examination of excised arteries of ten patients with intense femoral uptake of MDP showed arteriosclerosis and calcification in all cases. The findings suggest that the femoral visualization in delayed bone scans is probably related to arteriosclerosis and is not a non specific finding. There may be age-related differences in the distribution of MDP and DPD.


Regeneration of airway epithelial cells to study rare cell states in cystic fibrosis.
Pathological remodeling of the airway epithelium is commonly observed in cystic fibrosis (CF). Thus, tissue repair is critical to restore integrity and maintenance of the epithelial barrier function. Epithelial repair is a multi-step process initiated by progenitor cell migration into the injured area, proliferation, and re-differentiation into all of the cell types that contribute to the function of a normal airway epithelium. Recent technological advances applied to relevant animal and cell injury models have helped in understanding the complexity of progenitor cell differentiation. This short review will introduce the current knowledge of the mechanisms regulating airway epithelial cell (AEC) regeneration and repair, with a focus on the specification of two rare cell types/states: ionocytes and deuterosomal cells.


Primary mucosal melanoma of the eustachian tube.
Melanomas of the upper airway tract constitute around 1% of the total melanomas of the head and neck. They are usually more advanced in depth of invasion or size at the time of diagnosis than melanomas of the skin. The case of a 74-year-old Caucasian female with primary malignant melanoma of the left eustachian tube and bilateral neck metastasis is presented. The procedure from the diagnosis of neck metastasis to the location of the primary melanoma is described. The management of the malignant melanoma neck metastasis should also involve endoscopic examination of the upper aerodigestive tract, since the primary lesion can occur there.


Apolipoprotein J (clusterin) and Alzheimer's disease.
Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable of interacting with a broad spectrum of molecules. In pathological conditions, it is an amyloid associated protein, co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer's disease, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of action could be postulated to explain the role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti-apoptotic signal, (2) protection against oxidative stress, (3) inhibition of the membrane attack complex of complement proteins locally activated as a result of inflammation, and (4) binding to hydrophobic regions of partially unfolded, stressed proteins, and therefore avoiding aggregation in a chaperone-like manner. This review focuses on the association of apoJ in biological fluids with Alzheimer's soluble Abeta. This interaction prevents Abeta aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothelium.


SV40 DNA injected into Xenopus oocyte nuclei is transcribed by RNA polymerase B.
SV40 DNA I. injected into Xenopus oocyte nuclei is transcribed. The SV40-specific RNA molecules migrate on sucrose gradients as do viral RNAs formed in infected green monkey cells but a variable proportion of RNA sequences complementary to SV40 DNA is also found in the light region of the gradients. All SV40-specific RNA species seem to be synthesized by RNA polymerase B as their synthesis is completely sensitive to low concentrations (0.1 microgram/ml) of alpha-amanitin. Concomittantly, the formation of SV40-specific proteins (tumor antigens) is inhibited by injecting alpha-amanitin together with the SV40 DNA.


Temporary A-V sequential pacing using chest wall stimulation.
We describe the therapeutic application of chest wall stimulation enabling temporary A-V sequential pacing in patients with an implanted VVT pacemaker following the transvenous introduction of only one temporary electrode.


Functional annotation of proteins for signaling network inference in non-model species.
Molecular biology aims to understand cellular responses and regulatory dynamics in complex biological systems. However, these studies remain challenging in non-model species due to poor functional annotation of regulatory proteins. To overcome this limitation, we develop a multi-layer neural network that determines protein functionality directly from the protein sequence. We annotate kinases and phosphatases in Glycine max. We use the functional annotations from our neural network, Bayesian inference principles, and high resolution phosphoproteomics to infer phosphorylation signaling cascades in soybean exposed to cold, and identify Glyma.10G173000 (TOI5) and Glyma.19G007300 (TOT3) as key temperature regulators. Importantly, the signaling cascade inference does not rely upon known kinase motifs or interaction data, enabling de novo identification of kinase-substrate interactions. Conclusively, our neural network shows generalization and scalability, as such we extend our predictions to Oryza sativa, Zea mays, Sorghum bicolor, and Triticum aestivum. Taken together, we develop a signaling inference approach for non-model species leveraging our predicted kinases and phosphatases.


Polyphenolic-rich Cissus quadrangularis extract ameliorates insulin resistance by activating AdipoR1 in peri-/post-menopausal rats.
Insulin resistance (IR) is a significant complication in menopausal women, which predisposes them to cardiovascular disorder, obesity, and diabetes. Cissus quadrangularis is a polyphenolic plant rich in nutrients and is used as an edible vegetable in Nigeria. Previously, we investigated that C. quadrangularis extract (EECQ) treatment ameliorates IR, hyperlipidemia, and overweight in diabetic rats. Accordingly, in the current study, we further evaluated the adiponectin mimetic activity of EECQ in peri-/post-menopausal rats. Perimenopause was induced by High-fat diet/4-vinylcyclohexenediepoxide/(HFD-VCD), while postmenopause was by HFD/bilateral ovariectomy (HFD-OVX). Both the menopausal rats demonstrated an abnormal level of sex hormones, IR, hyperlipidemia, increased fat mass, and abnormal weight gain. Nevertheless, EECQ treated group revealed protection from these untoward complications. Furthermore, the docking score of major constituents of EECQ on adiponectin receptor 1 (AdipoR1) depicted a strong binding affinity, which was comparable to the ligand adipoRon. Besides, AdipoR1 expression determined by RT-PCR, Western blotting, and immunohistochemistry was downregulated in peri-/post-menopausal rats. Similarly, the expression of AdipoR1 downstream marker APPL1 and insulin sensitivity markers, including IRS1, Akt1, and GLUT4, were also dysregulated in menopausal rats. However, EECQ treated rats manifested restoration of normal expression of APPL1, IRS1, Akt1, and GLUT4 by upregulating AdipoR1. Altogether, the current study promulgated the adiponectin mimetic activity of EECQ, which is substantial to mitigate IR in menopausal conditions.


Antimicrobial resistance in cystic fibrosis: A Delphi approach to defining best practices.
Antimicrobial susceptibility testing (AST) is a cornerstone of infection management in cystic fibrosis. However, there is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment. It has been suggested there is a need for careful consideration of current AST use by the CF community. We engaged a group of experts consisting of pulmonary (adult and pediatric) and infectious disease clinicians, microbiologists, and pharmacists representing a broad international experience. We conducted an iterative systematic survey (Delphi) to determine and quantify consensus regarding key questions facing CF clinicians in the use of respiratory culture results including what tests to order, when to obtain them, and how to act upon the results of the testing. Consensus was reached for many questions but there was not universal agreement to the questions that were addressed. There were some differences with respect to cultures obtained for surveillance compared to when there is clinical worsening. Areas of general consensus include when and how respiratory cultures should be performed, what information should be reported, and when AST should be performed. A key finding is that clinical response to treatment is used to guide treatment decisions rather than AST results. Recommendations are presented regarding questions related to microbiology testing for patients with CF. We have also offered recommendations for priority research questions.


[Fatal catheter septicemia with finding of Candida lusitaniae].
A case of lethal pulmonary infection after catheter septicaemia with demonstration of C. lusitaniae in the blood is reported in a 73 year old patient with terminal Crohn's disease receiving long-term parenteral nutrition.


Outcomes of ring versus suture annuloplasty for tricuspid valve repair in patients undergoing mitral valve surgery.
There is controversy regarding the comparative effectiveness of methods of tricuspid valve (TV) repair-prosthetic ring versus suture annuloplasty-in patients undergoing operation for primary mitral valve (MV) disease. In this study, we analyzed factors associated with patient survival and recurrent tricuspid regurgitation (TR) following TV repair and focused on results stratified by method of tricuspid valve repair. We reviewed patients who underwent TV repair with suture (De Vega) or flexible ring annuloplasties at the time of MV surgery from 1995 to 2010. Patients with prior cardiac or concomitant aortic valve operations were excluded. Propensity matching was performed to account for potential differences in baseline characteristics between the groups. Primary outcomes were long-term mortality and postoperative TR grade. In the overall study, there were 415 patients with median age 72 years (range, 63-78 years), from which 148 matched pairs were identified by propensity score analysis. In the overall cohort, patients in the ring annuloplasty group more often had preoperative transvenous pacemakers (P = .05), lower ejection fractions (P = .028), and more recent years of operation (P < .001). For patients who had De Vega suture annuloplasty, long-term mortality was not different from that of patients who had ring annuloplasty (hazard ratio, 0.93; 95% confidence interval, 0.67-1.30). Older age, preoperative diabetes, and preoperative right ventricular dysfunction were predictors for long-term mortality. Durability of the annuloplasty methods was similar with no significant difference in trend of recurrent TR grades over follow-up (P = .807). Etiology of mitral regurgitation was not associated with recurrent TR during follow-up (P = .857). Late survival and TV durability following concomitant TV repair during MV surgery did not differ with respect to TV repair technique. In this series of patients with repaired tricuspid valves, etiology of MV disease did not influence postoperative changes in TR.


High-performance liquid chromatographic determination of hypoxanthine and xanthine in biological fluids.
A rapid and selective reversed-phase high-performance liquid chromatographic method for the simultaneous determination of hypoxanthine and xanthine in biological fluids was developed. The identification of hypoxanthine and xanthine was confirmed by xanthine oxidase reaction. This method was applied to the investigation of purine metabolism in subjects with xanthine oxidase deficiency or gout. Hypoxanthine concentrations three to ten times higher than those determined in plasma were found in erythrocyte samples from normal subjects and from patients with xanthine oxidase deficiency or hyperuricemia under allopurinol therapy.


Key comparison BIPM.RI(I)-K3 of the air-kerma standards of the NIST, USA and the BIPM in medium-energy x-rays.
A key comparison has been made between the air-kerma standards of the NIST, USA and the BIPM in the medium-energy x-ray range. The results show the standards to be in agreement at the level of the standard uncertainty of the comparison of 3.8 parts in 103, except at 250 kV where the difference is 1.5 times the standard uncertainty. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database.


Endotype-phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease.
Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable efficacy in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated ILD (SSc-ILD). We hypothesize that Nintedanib targeted molecular pathways will be augmented to a similar degree across PF-ILD regardless of aetiology. We collected explanted lung tissue at the time of lung transplantation from 130 PF-ILD patients (99 (76%) IPF, 14 (11%) SSc-ILD, 17 (13%) other PF-ILD), and wedge biopsies from 200 donor lungs and measured PDGF, FGF, VEGF and M-CSF concentrations by Luminex. The concentrations of PDGF-AA, PDGF-BB, FGF-2, VEGF and M-CSF were significantly increased in PF-ILD lungs compared to donor lungs (PDGF-AA 93·0 pg/ml [±97·2] vs. 37·5 pg/ml [±35·4], p < 0·001; PDGF-BB 102·5 pg/ml [±78·8] vs. 61·9 pg/ml [±47·0], p < 0·001; FGF-2 1442·4 pg/ml [±426·6] vs. 1201·7 pg/ml [±535·2], p = 0·009; VEGF 40·6 pg/ml [±20·1] vs. 24·9 pg/ml [±29·5], p < 0·001; and M-CSF 25526 pg/ml [±24,799] vs. 6120 pg/ml [±7245], p < 0·001). There were no significant differences in these growth factor/angiogenic molecules/cytokine concentrations when segregated by IPF, SSc-ILD and other PF-ILDs. Nintedanib specific targeted molecular pathways are augmented to a similar magnitude in all PF-ILD lung tissue as compared to controls, suggesting that Nintedanib treatment may be efficacious in PF-ILD regardless of aetiology. We speculate that clinical trials using Nintedanib for PF-ILD with or without IPF or SSc-ILD should show a similar relative reduction in FVC decline as seen in IPF and SSc-ILD (∼45-50%). Health Grant P01-HL108793 (JAB), South-Eastern Norway Regional Health Authority Grant 2018072 (AMHV).


Zygotic gene activation in the mouse embryo: involvement of cyclic adenosine monophosphate-dependent protein kinase and appearance of an AP-1-like activity.
Protein phosphorylation catalyzed by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is implicated in regulating zygotic gene activation in the two-cell mouse embryo (Poueymirou and Schultz; Dev Biol 133:588-599, 1989). We now provide evidence that H8, which is a PKA inhibitor, inhibits expression of an hsp70-driven beta-galactosidase reporter gene and that the concentration-dependence of this inhibition is similar to that for inhibiting expression of a stage-specific gene(s) that is a product of zygotic gene activation. We also demonstrate that neither cAMP nor serum can stimulate the expression, as detected by a histochemical assay, of a cAMP response element (CRE)- or serum response element (SRE)-driven beta-galactosidase reporter gene, respectively, in either germinal vesicle-intact oocytes or aphidicolin-arrested one-cell embryos that are chronologically at the tw-cell stage. In contrast, although 12-O-tetradecanoyl phorbol-13-acetate (TPA) does not stimulate expression of a TPA response element (TRE)-driven beta-galactosidase reporter gene in germinal vesicle-intact oocytes, it stimulates such expression in aphidicolin-arrested one-cell embryos. Moreover, TPA can stimulate the expression of either a CRE- or an SRE-driven beta-galactosidase reporter gene in such embryos. Results of these studies further implicate protein phosphorylation in regulating zygotic gene activation, along with its role in modulating enhancer function in the early mouse embryo.


Early sonographic detection of a 'human tail': a case report.
We report on a newborn in whom an echogenic protrusion arising in the caudal region was detected at 12 weeks' gestation. Subsequent ultrasound examinations at weeks 15 and 22 failed to demonstrate this finding. After birth, the infant was found to have a pilonidal sinus. The pilonidal sinus may represent a remnant of the embryonic appendage ('human tail') that usually disappears by the end of the 8th week of gestation. This case might support the theory of congenital pilonidal sinus origin.


Quantitative Global Survey Results of Acute Back Pain Sufferers Across Four Countries.
Surveys of back pain sufferers in the United States, China, Russia, and Germany were performed to better understand self-reported causes of acute nonspecific back pain and acute lower back pain among individuals engaging in sports and their preferred treatments. In each country, 1000 participants were surveyed (Step 1) to identify a population of nonspecific acute back pain sufferers, understand pain and treatment characteristics, and generate profiles for individuals with long-lasting (≥7 days) acute lower back pain. Subsequently, 200 participants with acute lower back pain episodes (7-21 days) and sports participation were identified in each country and completed surveys (Step 2) about sociodemographic, pain, treatment characteristics, and causes/triggers of long-lasting acute lower back pain episodes. In the United States, China, Russia, and Germany, respectively, 59%, 49%, 61%, and 63% of respondents reported ≥1 episode of nonspecific acute back pain in the previous 6 months. Average numbers of monthly nonspecific acute back pain episodes in the United States, Russia, Germany, and China were 2.5, 1.8, 1.3, and 0.8, respectively. Prevalence of acute lower back pain associated with sports/leisure activities ranged from 20% (Russia and Germany) to 46% (China). Onset of long-lasting acute lower back pain was between ages 30 and 33 years, limiting usual activities and reducing walking distance in 60% to 85% of respondents across all countries. Acute lower back pain started post-exercise within the first day for ≥75% of respondents. Most popular nonprescription and prescription treatments for acute lower back pain were creams/gels in Russia, creams/gels and oral painkillers in Germany, oral painkillers in the United States, and hot/cold patches in China. These results help to better understand acute back pain triggers, features, and treatment preferences among sports participants in different countries. Further research is warranted to develop preventative strategies. Not applicable.


Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis.
Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+ fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the importance of LIF signaling for HPA axis development.


Cellular-based modeling of oscillatory dynamics in brain networks.
Oscillatory, population activities have long been known to occur in our brains during different behavioral states. We know that many different cell types exist and that they contribute in distinct ways to the generation of these activities. I review recent papers that involve cellular-based models of brain networks, most of which include theta, gamma and sharp wave-ripple activities. To help organize the modeling work, I present it from a perspective of three different types of cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based modeling is taken to encompass the four features of experiment, model development, theory/analyses, and model usage/computation. The three modeling types are shown to include these features and interactions in different ways.


Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants.
In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow.


Do Carbon Nano-onions Behave as Nanoscopic Faraday Cages? A Comparison of the Reactivity of C60 , C240 , C60 @C240 , Li+ @C60 , Li+ @C240 , and Li+ @C60 @C240.
From the analysis of the polarizability of carbon nano-onions (CNOs), it was concluded that CNOs behave as near perfect nanoscopic Faraday cages. If CNOs behave as ideal Faraday cages, the reactivity of the C240 cage should be the same in Li+ @C240 and Li+ @C60 @C240 . In this work, the Diels-Alder reaction of cyclopentadiene to the free C240 cage and the C60 @C240 CNO together with their Li+ -doped counterparts were analyzed using DFT. It was found that in all cases the preferred cycloaddition is on bond [6,6] of type B of C240 . Encapsulation of Li+ results in lower enthalpy barriers due to the decrease of the energy of the LUMO orbital of the C240 cage. When the Li+ is placed inside the CNO C60 @C240 , the decrease in enthalpy barrier is similar to that of Li+ @C240 . However, the location of Li+ in Li+ @C240 (off-centered) and Li+ @C60 @C240 (centered) is quite different. When Li+ was placed in the center of the C240 cage in Li+ @C240 , the barriers increased significantly. Taking into account this effect, the barriers in Li+ @C240 and Li+ @C60 @C240 differ by about 4 kcal mol-1 . This result can be attributed to the shielding effect of C60 in Li+ @C60 @C240 . As a result, we conclude that this CNO does not act as a perfect Faraday cage.


Template method for fabricating Co and Ni nanoparticles/porous channels carbon for solid-state sodium-sulfur battery.
Room-temperature sodium/sulfur battery has raised concern due to the superiority of high theoretical capacity and low cost that promise for large-scale application. However, the sluggish electrochemical activity and "shuttle effect" limits the progress of practical application. This work designs a template method for constructing metal/carbon sulfur host, which possesses metal (Co, Ni) nanoparticles highly distributed in large amounts of porous channels in carbon sphere. The metal nanoparticles assist in sulfur immobilization, electric conductivity and catalyze reaction kinetics, meanwhile the hollow channels can buffer the volume change of sulfur. When testing as the liquid/solid-state room-temperature Na/S batteries, the S@Co/C and S@Ni/C electrodes deliver high capacities and rate capability. This template method possesses utility potential in developing high-powered RT Na/S batteries, which provides possibility to for the preparation of various electrode materials in battery technology.


Coffee bean arabinogalactans: acidic polymers covalently linked to protein.
The arabinogalactan content of green coffee beans (Coffea arabica var. Yellow Caturra) was released by a combination of chemical extraction and enzymatic hydrolysis of the mannan-cellulose component of the wall. Several arabinogalactan fractions were isolated, purified by gel-permeation and ion-exchange chromatography and characterised by compositional and linkage analysis. The AG fractions contained between 6 and 8% glucuronic acid, and gave a positive test for the beta-glucosyl-Yariv reagent, a stain specific for arabinogalactan-proteins. The protein component accounted for between 0.5 and 2.0% of the AGPs and contained between 7 and 12% hydroxyproline. The AG moieties displayed considerable heterogeneity with regard to their degree of arabinosylation and the extent and composition of their side-chains. They possessed a MW average of 650 kDa which ranged between 150 and 2000 kDa. An investigation of the structural features of the major AG fraction, released following enzymatic hydrolysis of the mannan-cellulose polymers, allowed a partial structure of coffee arabinogalactan to be proposed.


Examination of some factors that control the effects of septal lesions on lordosis behavior.
Various experimental parameters related to the effects of septal lesions on the lordosis behavior of rats have been examined. First, the failure of septal lesions to facilitate lordosis behavior in male rats appears to be related to the degree of exposure to androgens neonatally. The normal facilitation in lordosis behavior associated with septal destruction in adult female rats does not occur if these female rats are treated with 1.0 mg of testosterone propionate (TP) on Day 1 of life. Yet female rats given 270 mug of TP on Day 3 of life respond the same as do normal females to septal lesions. Second, these sexually dimorphic effects of septal lesions can be modified in adult rats by chronic treatment with gonadal hormones following septal destruction. Whereas previous studies indicated that chronic estrogen injections permit a facilitation in lordosis behavior to occur in septal lesioned male rats, the present results showed that chronic injections of TP following a septal lesion attenuates the facilitation in lordosis behavior typically observed in adult female rats following a septal lesion. Third, examination of the time course for the facilitation in lordosis behavior following a septal lesion revealed a four to six day delay before the appearance of heightened female sexual behavior. Fourth, in support of the possibility that modifications in lordosis behavior by septal lesions may be mediated by a depletion or imbalance in brain amines, amphetamine was found to reduce the high levels of lordosis behavior of septal lesioned female rats to control levels. Finally, further evidence of a potential role for brain amines in the effects of septal lesions was provided by the observation of significantly lower content and turnover of dopamine in the amygdala of septal lesioned female rats, relative to sham operated controls.