Aeromonas hydrophila exotoxin induces cytoplasmic vacuolation and cell death in VERO cells.
Many organisms are able to cause cell vacuolation, but it is unclear if this can be considered a step of apoptosis or necrosis, or a distinct form of cell death. In this study VERO cells were used to evaluate the relationship between vacuolation and cell death pattern caused by exotoxins produced by environmental strains of A. hydrophila. Cell damage has been evaluated morphologically as well as biochemically. Cytotoxic and vacuolating titres were strictly correlated and the vacuolation has to be considered an early indicator of cytotoxicity that causes cell apoptosis or necrosis in relation to the dose. Signs of apoptosis (chromatin condensation and blebbing) were observed at low concentration and TGase activity, referable to apoptosis induction, confirms morphological observations. In fact, putrescine incorporation was related both to cytotoxin concentration and time of incubation. Moreover, the observed doubling cells with necrotic features permit us to suppose that cell sensitivity and death pattern could change during the different phases of cellular cycle.


Arabidopsis thaliana: a new test species for phytotoxic bioassays.
Lettuce seeds (Lactuca sativa L.) and other crop species are often used in phytotoxic bioassays that are designed to detect allelochemicals. The seeds of these species are considered ideal because they are readily available, germinate rapidly and uniformly, and are routinely used in laboratories around the world. Despite their common use, however, the seeds of these species are often not as sensitive or responsive to some phytotoxic chemicals as are the seeds of other species. While searching for a more sensitive test species for phytotoxic bioassays, the Columbia ecotype of Arabidopsis thaliana exhibited greater sensitivity to seven potent allelochemicals than did lettuce seeds, which, in some cases, did not respond at all to those substances. Sensitivity satisfies one of the criteria for selecting a test species for bioassays. We now report on the results of our study and offer additional reasons for using A. thaliana seeds.


Early events in HIV transmission through a human reconstructed vaginal mucosa.
The early steps of HIV entry into intact vaginal mucosa still need to be clarified. Here we investigated how HIV translocated across the vaginal pluristratified epithelium, either by transcytosis or by uptake in Langerhans cells. Using human primary fibroblasts and vaginal epithelial cells, we developed an in-vitro model of vaginal mucosa in which Langerhans cells could also be integrated. Owing to the absence of T lymphocytes and macrophages, we specifically studied the role of Langerhans cells in HIV transmission and the transcytosis of cell-associated HIV. Our model has a normal mucosal tissue architecture and Langerhans cells were efficiently integrated within the pluristratified epithelium. In addition, tight junction proteins' expression, high transepithelium resistance and low fluorescein isothiocyanate-BSA passage confirmed the integrity and impermeability of the reconstruction. Furthermore, we showed that human Langerhans cells also expressed tight junction proteins. Then, we demonstrated that neither transcellular nor intercellular transport of free infectious virus released by R5-infected or X4-infected peripheral blood mononuclear cells inoculated apically occured in the vaginal mucosa, irrespective to the presence of Langerhans cells. For the first time, we documented that, within 4 h following contact with HIV-infected cells, translocation of free HIV particles across a pluristratified mucosa is not detectable and that, in this context, it seemed that Langerhans cells do not increase HIV transmission. Moreover, we provided a useful model for the development of strategies preventing HIV entry into the female genital tract, especially for testing the efficiency of various microbicides.


Synthesis of Cyclic Peptide Mimetics by the Successive Ring Expansion of Lactams.
A successive ring-expansion protocol is reported that enables the controlled insertion of natural and non-natural amino acid fragments into lactams. Amino acids can be installed into macrocycles via an operationally simple and scalable iterative procedure, without the need for high dilution. This method is expected to be of broad utility, especially for the synthesis of medicinally important cyclic peptide mimetics.


[Optimization of preparation procedures of tanshinone-ⅡA /β-cyclodextrin inclusion complex and dissolution study of tanshinone-ⅡA in vitro].
In this paper, tanshinone-ⅡA (Tan-IIA)/β-cyclodextrin (β-CD) inclusion complexes were prepared by saturated aqueous solution method. Based on the single factor experiment, Box-Benhnken design and response surface method were utilized to optimize the preparation procedures of tanshinone-ⅡA/β-cyclodextrin inclusion complexes. The ratio of β-CD to Tan-ⅡA, experimental temperature and time were defined as independent variables, while the yield of the inclusion complexes, encapsulation efficiency and the generalized "normalized value" were set as the response value. In addition, the inclusion complexes were characterized by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The results showed that optimum preparation conditions for Tan-ⅡA/β-CD inclusion complex were as follows: Tan-ⅡA/β-CD ratio of 1:7, the temperature of 48 ℃ and the time of 3 h. Under the optimized conditions, the encapsulation efficiency of Tan-ⅡA/β-CD inclusion complex was 84.75%. The Tan-IIA and β-CD inclusion complex can significantly improve the dissolution of Tan-ⅡA.


Ethynylglycine synthon, a useful precursor for the synthesis of biologically active compounds: an update. Part II: synthetic uses of ethynylglycine synthon.
The ethynylglycine synthon {(R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-ethynyl-oxazolidine} is a chiral compound with valuable synthetic interest. An update (covering literature from 2005 to 2017) on the different synthetic utilities is reviewed and discussed.


Surgical Treatment of Aggressive Intraosseous Cavernous Hemangioma in Maxilla Through Surgical Resection.
Hemangiomas are benign vascular lesions characterized by endothelial vascular proliferation and may demonstrate aggressive clinical features. Intraosseous hemangiomas are uncommon and the maxillary location rare, with few cases described in the literature. The treatment of these lesions varies, however they have a better prognosis when a surgical treatment through resection is performed. The aim of this study is to report a case of right maxillary cavernous intraosseous hemangioma treated by surgical resection with previous embolization. The diagnosis was made through incisional biopsy and immunohistochemical examination. An aggressive lesion profile was observed through the Ki67 marker. During surgery, a temporary ipsilateral external carotid artery ligation was performed to minimize possible bleeding. Weber-Fergson surgical access was performed and total surgical resection through hemi-maxillectomy. The patient is stable after 30 months of follow-up without relapses. In suspected cases of intraosseous hemangiomas, accurate diagnosis and total surgical resection of the lesion is essential. The use of therapeutic mammoths that minimize sagging during and after the procedure such as embolization and arteriography should always be performed.


Mixed pulmonary infection in an immunocompromised patient: a rare case report.
Patients who are immunocompromised are predisposed to a variety of common and uncommon pulmonary infections. We report a case of mixed pulmonary infection by drug resistant tuberculosis with a nocardiosis in a 49-year-old man who was a known case of chronic obstructive pulmonary disease, on prolonged corticosteroid use with diabetes mellitus. Chronic use of corticosteroids is a predisposing factor for opportunistic infections, such as nocardiosis or tuberculosis. Since such a mixed infection is rare, maybe a combined approach to therapy early in the course of disease would be effective in such cases.


LaeA control of velvet family regulatory proteins for light-dependent development and fungal cell-type specificity.
VeA is the founding member of the velvet superfamily of fungal regulatory proteins. This protein is involved in light response and coordinates sexual reproduction and secondary metabolism in Aspergillus nidulans. In the dark, VeA bridges VelB and LaeA to form the VelB-VeA-LaeA (velvet) complex. The VeA-like protein VelB is another developmental regulator, and LaeA has been known as global regulator of secondary metabolism. In this study, we show that VelB forms a second light-regulated developmental complex together with VosA, another member of the velvet family, which represses asexual development. LaeA plays a key role, not only in secondary metabolism, but also in directing formation of the VelB-VosA and VelB-VeA-LaeA complexes. LaeA controls VeA modification and protein levels and possesses additional developmental functions. The laeA null mutant results in constitutive sexual differentiation, indicating that LaeA plays a pivotal role in inhibiting sexual development in response to light. Moreover, the absence of LaeA results in the formation of significantly smaller fruiting bodies. This is due to the lack of a specific globose cell type (Hülle cells), which nurse the young fruiting body during development. This suggests that LaeA controls Hülle cells. In summary, LaeA plays a dynamic role in fungal morphological and chemical development, and it controls expression, interactions, and modification of the velvet regulators.


Effect of 6-min Walk Test on pro-BNP Levels in Patients with Pulmonary Arterial Hypertension.
Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions. Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30 days or more were enrolled. After resting the patient for 30 min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2 h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student's paired t tests. There were 17 females and 3 male subjects. The mean age was 53 ± 11 years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50 ± 15 mmHg with a mean pulmonary vascular resistance of 10 ± 4 Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377 ± 140 m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1 h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2 h post 6MWT. There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1 h. Pro-BNP levels then return to baseline at 2 h post 6MWT.


Spatial distribution of mosquito larvae and the potential for targeted larval control in The Gambia.
We examined the distribution of aquatic stages of malaria vectors in a 400-km(2) area in rural Gambia to assess the practicality of targeting larval control. During the rainy season, the peak period of malaria transmission, breeding sites were 70% more likely to have anopheline larvae in the floodplain of the Gambia River than upland sites (P < 0.001). However, mosquitoes were found in some examples of all habitats, apart from moving water. Habitats most often colonized by anopheline larvae were the largest water bodies, situated near the landward edge of the flood-plain, where culicine larvae were present. In the wet season, 49% of sites had anophelines versus 19% in the dry season (P < 0.001). Larval control targeted at specific habitats is unlikely to be successful in this setting. Nonetheless, larval control initiated at the end of the dry season and run throughout the rainy season could help reduce transmission.


The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL).
Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that is secreted mostly by immune cells such as neutrophils, macrophages, and dendritic cells. Its production is stimulated in response to inflammation. The concentrations of NGAL can be measured in plasma, urine, and biological fluids such as peritoneal effluent. NGAL is known mainly as a biomarker of acute kidney injury and is released after tubular damage and during renal regeneration processes. NGAL is also elevated in chronic kidney disease and dialysis patients. It may play a role as a predictor of the progression of renal function decreases with complications and mortality due to kidney failure. NGAL is also useful in the diagnostic processes of cardiovascular diseases. It is highly expressed in injured heart tissue and atherosclerostic plaque; its serum concentrations correlate with the severity of heart failure and coronary artery disease. NGAL increases inflammatory states and its levels rise in arterial hypertension, obesity, diabetes, and metabolic complications such as insulin resistance, and is also involved in carcinogenesis. In this review, we present the current knowledge on NGAL and its involvement in different pathologies, especially its role in renal and cardiovascular diseases.


Modeling the Temporal Evolution of Postoperative Complications.
Post-operative complications have a significant impact on patient morbidity and mortality; these impacts are exacerbated when patients experience multiple complications. However, the task of modeling the temporal sequencing of complications has not been previously addressed. We present an approach based on Markov chain models for characterizing the temporal evolution of post-operative complications represented in the American College of Surgeons National Surgery Quality Improvement Program database. Our work demonstrates that the models have significant predictive value. In particular, an inhomogenous Markov chain model effectively predicts the development of serious complications (coma longer than a day, cardiac arrest, myocardial infarction, septic shock, renal failure, pneumonia) and interventional complications (unplanned re-intubation, longer than 2 days on a ventilator and bleeding transfusion).


Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice.
Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30-50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50-75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor-alpha coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30-78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency (P=0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function.


Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America.
Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.


Common features in DNA recognition helices of eukaryotic transcription factors.
Eukaryotic transcription factors which use an alpha-helix for DNA recognition, including the leucine zipper and homoeo domain proteins, have common features in the amino acid sequence of the DNA recognition helix, and also in the way this helix interacts with DNA. These factors all share a similar 12 residue segment in the DNA recognition helix, which is named the probe helix, since it covers all the pertinent interactions. Moreover, in all cases the interactions can be divided into two parts: the Arg/Lys residues at positions 7, 9, 11 and 12 in the C-terminal half of the segment contact phosphate groups, whereas the N-terminal half interacts with the DNA bases by using residues at positions 1, 4, 5 and 8. The residue occupying position 1 is the most important for sequence specific DNA recognition. Similar 12 residue sequences are found in the DNA binding domain of many transcription factors including those of the TEA family, the Myc type of bHLH family, the MADS family, the Ets family and the OmpR family. These generalities show that it might be possible to find a stereochemical code which explains three-dimensional interactions between DNA and an alpha-helix of this type.


Using IFN-gamma release assay to confirm tuberculin skin test improves the screening of latent tuberculosis infection in Italian healthcare workers.
Healthcare workers (HCWs) represent a tuberculosis (TB) risk group for a wide range of tasks in healthcare, even in countries with low TB incidence, like Italy. Latent Tuberculosis Infection (LTBI) screening programs are an important tool for TB prevention in these setting. A retrospective study under a LTBI screening program among HCWs at the Siena University Hospital (Italy), was conducted between September 2011 and July 2015. Tuberculin Skin Test (TST) was used as a first level examination; all TST-positive cases were tested with QuantiFERON-TB Gold In-Tube (QFT-GIT) test, together with a group of TST-negative subjects. Among the 2136 HCWs screened, 144 (6.7 %) were TST-positive and therefore tested with QFT-GIT, confirming a positive result in 36 cases (25 %). Agreement between two tests was poor (k = 0.092; 95 %, Confidence Interval [CI]- 0.048-0.136, p = 0.002). Among TST-positive cases, discordant results occurred more frequently in BCG vaccinated than unvaccinated HCWs (86.3 %, p < 0.001). The probability of a QFT-GIT-positive result increased according to the TST diameter (p = 0.001). No putative risk factor was associated with LTBI occurrence. The use of QFT-GIT test as a second step in TST-positive cases offers an appropriate tool for LTBI detection, especially among BCG-vaccinated HCWs.


Immune cells and signatures characterize tumor microenvironment and predict outcome in ovarian and endometrial cancers.
Aims: We investigated immunogenomic signatures and correlated them with survival in ovarian cancer (OV) and endometrial cancer (EC). Materials & method: We used whole transcriptome sequencing data from uterine serous cancer and The Cancer Genome Atlas data of OV and EC (n = 719). Gene expression score was calculated. Population abundance of immune cells were estimated. Results: TGF-β, myeloid cells, IFN-γ, T cells, B cells and endothelial cells predicted overall survival. Whereas CD47, neutrophils and endothelial cells predicted progression-free survival. In multivariate analyses, TGF-β, CD47 and monocytic cells predicted survival in high levels of microsatellite instability (MSI-H) EC whereas high IFN-γ trended toward improved survival in the MSI-S EC. High IFN-γ/low TGF-β and high IFN-γ/low CD47 signatures predicted longer overall survival. Low TGF-β/low CD47 signature predicted longer overall survival only in the MSI-H EC. Conclusion: Our data support the role of immune markers in predicting survival in OV/EC.


Characterization of dopamine transport in crude synaptosomes prepared from rat medial prefrontal cortex.
Accumulating evidence suggests that dopamine (DA) uptake into mesocortical neurons may be regulated through mechanisms that are markedly different from those observed in nigrostriatal or mesoaccumbens systems. The current studies were conducted to develop a rapid and sensitive DA uptake assay in crude synaptosomes prepared from the medial prefrontal cortex (mPFC) of a single animal. Uptake of DA into the mPFC was saturable, linear with respect to protein concentration, time dependent, and sensitive to the effects of monoamine transport inhibitors. Saturation analysis revealed the K(m) and V(max) values for DA transport in the mPFC were approximately 60 nM and 6.5 pmol/min mg protein, respectively. A significant amount of DA uptake in the mPFC was more sensitive to inhibition by nisoxetine compared to GBR12909, fluoxetine (FLX), and cocaine (COC), suggesting the norepinephrine transporter (NET) plays an important role in the clearance of DA within this region. The described assay conditions would be useful in examining DA uptake within specific brain regions obtained from a single animal.


[Seven questions for elderly in the practice of primary care physicians].
Although geriatric syndromes are widespread, they often remain undiagnosed leading to the development of adverse outcomes. For the prompt detection of the most common geriatric syndromes in primary care we have created seven issues related to weight loss, vision and hearing impairments, falls, mood disorder, cognitive impairment, urinary incontinence, and the difficulties in walking. We believe that using of these questions will allow physicians to focus on addressing the important health problems associated with age and will produce the selection of patients for comprehensive geriatric assessment.


Comparison of temperature change among different adhesive resin cement during polymerization process.
The aim of this study was to assess the intra-pulpal temperature changes in adhesive resin cements during polymerization. Dentin surface was prepared with extracted human mandibular third molars. Adhesive resin cements (Panavia F 2.0, Panavia SA, and RelyX U200) were applied to the dentin surface and polymerized under IPS e.max Press restoration. K-type thermocouple wire was positioned in the pulpal chamber to measure temperature change (n = 7). The temperature data were recorded (0.0001 sensible) and stored on a computer every 0.1 second for sixteen minutes. Differences between the baseline temperature and temperatures of various time points (2, 4, 6, 8, 10, 12, 14, and 16 minute) were determined and mean temperature changes were calculated. At various time intervals, the differences in temperature values among the adhesive resin cements were analyzed by two-way ANOVA and post-hoc Tukey honestly test (α = 0.05). Significant differences were found among the time points and resin cements (P < 0.05). Temperature values of the Pan SA group were significantly higher than Pan F and RelyX (P < 0.05). Result of the study on self-adhesive and self-etch adhesive resin cements exhibited a safety intra-pulpal temperature change.


A phase II study of paclitaxel and cisplatin combination chemotherapy in recurrent or metastatic head and neck cancer.
The taxanes are the most active new agents for squamous-cell carcinoma of the head and neck (SCCHN) since the discovery of cisplatin. Our aim was to define the therapeutic efficacy and toxicity of paclitaxel and cisplatin combination therapy in patients with recurrent SCCHN. Patients with locally recurrent or metastatic SCCHN were enrolled in the study. Patients were required to be chemotherapy-naive, and should have completed radiation therapy at least 6 weeks prior to enrollment. A World Health Organization (WHO) performance status of less than 3 was required. Paclitaxel (Taxol, Bristol Myers Squibb Company, Princeton, NJ) and cisplatin therapy (PC) consisted of prophylaxis with pheniramine 50 mg i.v., ranitidine 150 mg i.v. and dexamethasone 20 mg i.v. given prior to paclitaxel 175 mg/m2 as a 3-hour i.v. infusion, followed by cisplatin 75 mg/m2 as a 1-hour infusion with an additional 3000 cc of saline for hydration. This treatment was repeated every 3 weeks for a maximum of six cycles. Patients were evaluated for response after the third and sixth cycles, or at the time of clinical progression. Fifty patients were enrolled in the study. The overall response rate was 32% with a 10% complete response rate. Forty-eight patients were assessable for toxicity. A total of 221 cycles of chemotherapy was given and the most common toxicity was myelosuppression; 7.7% of cycles had grade III-IV neutropenia. Severe neuropathy, nephropathy, mucositis, and emesis were uncommon (<10 %). At a median follow-up period of 25 months, the median overall survival was 10 months and the 1-year progression-free and overall survival rates were 16.7% and 35.2%, respectively. We conclude that patients with recurrent SCCHN have a moderate response to combination chemotherapy with cisplatin and paclitaxel. Given this moderate response rate, it is unlikely that this combination (PC) might ultimately prove to be superior to standard treatment regimens in terms of significant survival advantage.


The moderating role of attention-deficit/hyperactivity disorder in the work engagement-performance process.
Attention-deficit/hyperactivity disorder (ADHD) is a cognitive disability that affects millions. Although individuals with ADHD are employed throughout many organizations and there is evidence that their performance is lower, scant research exists describing how ADHD impacts an individual's performance. In this article, we extend attentional control theory to examine how ADHD impacts both the effectiveness and efficiency of employee performance. Across 3 samples, 2 of general working adults (n = 257 and 170) and 1 of nurses (n = 243), we found that ADHD was associated with lower performance (rated via self-, coworker, and supervisor ratings) and that the relationship was strongest for in-role performance, suggesting that employees with ADHD may be diverting attention away from task-relevant behaviors. Furthermore, although work engagement was associated with higher performance, that relationship was diminished among those who experienced higher levels of ADHD, suggesting lower performance efficiency. We discuss the implications of these findings for research on attentional control and the management of those with ADHD at work.


[Evaluation on the Impacts of Different Background Determination Methods on CO2 Sources and Sinks Estimation and Seasonal Variations].
To accurately determine background conditions or extract sources and sinks information from the observed atmospheric carbon dioxide (CO2) concentration is crucial for quantitative estimation of regional and global carbon budget and future trends of atmospheric CO2. In this study, the synchronized observed surface winds and carbon monoxide (CO) concentration have been examined to test their effectiveness as filter factors to determine CO2 background conditions at Waliguan site. The results show that the surface winds and CO concentrations can be used as filter factor in winter, but they are not very effective in summer. Three statistical methods, robust estimation of background signal (REBS), Fourier transform algorithm (FTA) and a new developed moving average filtering (MAF), are applied to atmospheric CO2 background selection. The result suggested that our new developed MAF method, which can well estimate the elevated and sequestered CO2 concentrations due to using changing and adjusting filter criteria at every two-week fitting window, is thus better than the other two statistical methods. A good consistency is indicated by the three methods for estimating the elevated CO2 caused by local or regional emissions, but it showed large discrepancies when determining the sequestered CO2. The result suggested that the three methods can reasonable extract those anthropogenic influenced episodes, but only MAF method would well identify those episodes due to terrestrial CO2 fluxes. Mean seasonal amplitude of atmospheric CO2 at Waliguan during 1995-2008 is 10. 3 x 10(-6) estimated by MAF method, which is in good agreement with previous studies. Whereas, the seasonal amplitudes derived by REBS method are much lower, only with a value of ~9. 1 x 10(-6) during 1995-2008, which will result in an underestimation of regional or global CO2 fluxes.


A Study on the Relationship between Sense of Disease Uncertainty and Family Strength and Mental Resilience in Guardians of Children with Inflammatory Bowel Disease.
Inflammatory bowel disease is difficult to cure, which seriously affects the physical and mental health of children and brings negative psychological stress to guardians. Uncertainty in illness of guardians reduces the ability of care and is not conducive to the treatment and recovery of children. Therefore, it is of great significance to explore the related factors of uncertainty in illness. The aim of this study is to explore the relationship between sense of disease uncertainty and family strength and mental resilience in guardians of children with inflammatory bowel disease (IBD). A total of 146 guardians of 88 children with inflammatory bowel disease were investigated. The guardians' sense of disease uncertainty, family strength, and mental resilience were evaluated by Mishel uncertainty in illness scale-family member (MUIS-FM), family hardiness index (FHI), and Connor-Davidson resilience sca1e (CD-RISC), respectively. Spearman correlation was used for analyzing the correlation between the guardian's sense of disease uncertainty and family resilience. The guardian's MUIS-FM score from lowest to highest was complexity, unpredictability, lack of information, and uncertainty. The average scores of FHI and CD-RISC were lower than the average score of CD-RISC of the general community in China 65.4 (t = -4.36, P < 0.05). The score of MUIS-FM was significantly correlated with the scores of FHI and CD-RISC (P < 0.05). Multiple linear regression analysis showed that the challenge score in the FHI scale and the fortitude score and the strength score in the CD-RISC scale were the main influencing factors of guardians' sense of disease uncertainty in children with IBD (P < 0.05). The guardians of children with IBD had a more serious sense of disease uncertainty, which was related to family strength and mental resilience.


Role of ATP sensitive potassium channels in long term adaptation to metabolic stress.
Cardiac KATP channel activation during metabolic inhibition has been implicated in effects ranging from malignant arrhythmogenesis and sudden cardiac death to reduction in infarct size, preconditioning, and a more rapid recovery of contractile ability. Given these disparate consequences, and the repeated observation that KATP currents are altered under a wide variety of metabolically stressful conditions, it becomes increasingly more critical to determine whether the changes described are part of the underlying pathology, or whether they reflect an endogenous adaptation to protect cardiac function. We support the view that enhanced KATP channels are intrinsically altered during long term metabolic inhibition, at least in part through a reduction in channel sensitivity to ATP, and that the change manifests itself in most cases as an adaptive mechanism. Increased channel activity in a chronically ischaemic environment could serve to maintain resting potential, limit calcium influx, conserve [ATP]i, and prevent excessive prolongation of action potential duration.


Reduction in postsynaptic inhibition during maintained electrical stimulation of different nerves in the cat hindlimb.
1. Steady-state postsynaptic potentials (PSPs) were generated by prolonged (approximately 1 s) high-frequency (100-200 Hz) electrical stimulation of nerves in the cat hindlimb. The characteristics of these steady-state PSPs were compared for two polysynaptic afferent pathways (ipsilateral cutaneous sural vs. contralateral peroneal nerves), two animal preparations (decerebrate vs. chloralose), and two motoneuron pools (medial gastrocnemius vs. lateral gastrocnemius-soleus). 2. PSPs from both nerves usually (36 of 51 cases) contained a mixture of depolarizing and hyperpolarizing components. In all 36 cases where the PSP contained a hyperpolarizing component, a consistent qualitative pattern emerged during prolonged stimulation: the hyperpolarization reached a peak approximately 20 ms after stimulation onset and then decayed with a biphasic time course that consisted of an initial rapid phase (20-40 ms) and a later slower phase (200-400 ms) before the steady-state value was reached. This pattern occurred regardless of the differences in polysynaptic afferent pathways, animal preparations, and motoneuron pools. 3. The consistency of this overall pattern was remarkable, given the existence of several quantitative differences among the PSPs. These differences include the following: hyperpolarizing components were least common in the sural and peroneal PSPs in the decerebrate preparation. And only these sural and peroneal PSPs tended to have prolonged afterpotentials after stimulus cessation. The steady-state sural PSPs in the decerebrate preparation tended to generate the largest PSPs and, moreover, these PSPs did not follow the overall trend of having a statistically significant relation between the amplitude of the initial hyperpolarization and the amount of its decay. Finally, transient sural PSPs in lateral gastrocnemius-soleus motoneurons in the decerebrate preparation tended to have the largest hyperpolarizations. 4. To determine whether the decay of the hyperpolarization and the subsequent dominance of depolarization was due to a decreased inhibition or an increased excitation, injected current pulses were utilized to measure the changes in the cell's input resistance during the course of the synaptic input. A strong decrease in input resistance accompanied the initial period of maximal hyperpolarization (50% with respect to the resting input resistance). Input resistance then returned toward resting values as hyperpolarization faded and depolarization became dominant. However, there remained a persistent decrease in input resistance during the final phase of the PSP that amounted to < 10% of the initial decrease. These findings indicated that much of the reduction in hyperpolarization reflected a progressive decrease in synaptic efficacy for the inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)


Anti-Biofouling and Desalination Properties of Thin Film Composite Reverse Osmosis Membranes Modified with Copper and Iron Nanoparticles.
The anti-biofouling and desalination properties of thin film composite reverse osmosis membranes (TFC-RO), modified by the incorporation of copper and iron nanoparticles, were compared. Nanoparticles of metallic copper (CuNPs) and an iron crystalline phase mix (Fe and Fe2O3, FeNPs) were obtained by oxide-reduction-precipitation and reduction reactions, respectively, and characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Modified membranes (PA+0.25Cu-PSL and PA+0.25Fe-PSL) were obtained by incorporating these nanoparticles during the interfacial polymerization process (PI). These membranes were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and contact angle measurements. Bactericidal tests by a Colony Forming Unit (CFU) were performed using Escherichia coli, and anti-adhesion properties were confirmed by fluorescence microscopy estimating the percentage of live/dead cells. The permeate flow and rejection of salts was evaluated using a crossflow cell. An increase of the membrane's roughness on the modified membrane was observed, influencing the desalination performance more strongly in the presence of the FeNPs with respect to the CuNPs. Moreover, a significant bactericidal and anti-adhesion effect was obtained in presence of both modifications with respect to the pristine membrane. An important decrease in CFU in the presence of modified membranes of around 98% in both modifications was observed. However, the anti-adhesion percentage and reduction of live/dead cells were higher in the presence of the copper-modified membrane in comparison to the iron-modified membrane. These facts were attributed to the differences in antimicrobial action mechanism of these types of nanoparticles. In conclusion, TFC-RO membranes modified by the incorporation of CuNPs during PI represent one alternative material to attend to the biofouling impact in the desalination process.


Relative survival of cancer patients--a comparison between Denmark and the other Nordic countries.
The results of a Nordic collaborative project revealed that Danish cancer patients had a poorer prognosis than patients in the other Nordic countries for some major cancer sites. The present study was undertaken to further explore the differences in survival between Denmark and the other Nordic countries. All cancer cases diagnosed in the Nordic countries during 1958 to 1991/92 were included in the analysis. Relative survival and excess mortality were calculated for intervals in the first five years after diagnosis. Since the 1950s, the prognosis of cancer patients has improved in all the countries, but more moderately in Denmark. For cancers of the stomach, colon, rectum, breast (female), and prostate, the Danish patients had a markedly lower relative survival than the patients in the other countries. They also had the lowest proportion of localized tumours. It appears that Danish cancer patients are diagnosed at a later stage of disease than patients in the other Nordic countries.


Role of animal models for percutaneous atrial septal defect closure.
As for any preclinical development of new implantable device, bench testing has been followed by experimental studies on large animal models for the development of atrial septal defect closure devices. Various models have been used according to studied species (porcine, ovine or canine model) and whether the septal defect was percutaneously or surgically created. Animal models of percutaneous atrial septal defect closure aim to assess the healing process and device endothelialisation, as well as the development of magnetic resonance imaging guided procedures, the short-term effects of volume overload on right ventricular contractility through haemodynamic studies and the understanding of other complications such as nickel hypersensitivity. Each technique has its own advantages and drawbacks, and leads to different punch-related, acute septal injuries that could have an effect on the healing process after device implantation. It has been suggested that some long-term, major device-related complications such as thrombosis or infective endocarditis may be associated with an inappropriate healing process or insufficient endothelialisation of the device, leading industrial companies to pay a great deal of attention to the healing process. Tissue reactions in animal models were shown to adequately reproduce the healing response after device implantation in humans, with an endothelial device coverage observed as early as 30 days after implantation and complete after 3 to 6 months. Research perspectives may evaluate both animal models and in-vitro studies in parallel with a view to clarify the endothelialisation process using human endothelial cells through in-vitro experiments. Self-sensing device for detecting the presence of endothelial cells on the surface of intracardiac occluders and high-resolution imaging techniques that could non-invasively assess the complete endothelialisation of a device would also be promising tools which would need large animal models studies before their clinical application.


The Role of Learning Support and Chat-Sessions in Guided Internet-Based Cognitive Behavioral Therapy for Adolescents With Anxiety: A Factorial Design Study.
Increased awareness of anxiety in adolescents emphasises the need for effective interventions. Internet-based cognitive behavioural therapy (ICBT) could be a resource-effective and evidence-based treatment option, but little is known about how to optimize ICBT or which factors boost outcomes. Recently, the role of knowledge in psychotherapy has received increased focus. Further, chat-sessions are of interest when trying to optimize ICBT for youths. This study aimed to evaluate the role of learning support and chat-sessions during ICBT for adolescent anxiety, using a factorial design. A total of 120 adolescents were randomised to one of four treatment groups, in a 2x2 design with two factors: with or without learning support and/or chat-sessions. Anxiety and depressive symptoms were reduced (Beck Anxiety Inventory- BAI; Cohen's d =0.72; Beck Depression Inventory- BDI; d =0.97). There was a main effect of learning support on BAI (d =0.38), and learning support increased knowledge gain (d =0.42). There were no main effects or interactions related to the chat-sessions. Treatment effects were maintained at 6-months, but the added effect of learning support had by then vanished. ICBT can be an effective alternative when treating adolescents with anxiety. Learning support could be of importance to enhance short-term treatment effects, and should be investigated further.


In vitro fertilization outcomes in women with antiphospholipid antibodies circulation.
Background: Antiphospholipid antibodies (aPL) have a multifaceted effect on the hemostatic system, damaging all its protective links.Aim: To study the effect of APA on outcomes of assisted reproductive technologies (ART).Study design: We examined 267 women with infertility, who planned pregnancy using ART. They included 178 women with IVF failure (I group) and 89 women with pregnancy after the IVF program (II group). The comparison group consisted of 80 pregnant women after IVF (male factor); a control group included 80 pregnant women with physiological pregnancy. Results of study demonstrated a high frequency of aPL circulation in a group of women with IVF failures. Overall, the proportion of aPL among all 267 women who planned pregnancy with ART was 32.6%. Elevated levels of aPL in the structure of causes of IVF failures (group I) were observed in 42.1% of them. Among women whose pregnancy occurred with ART (II group) the rate of APA was 19.1%. In the comparison group, in 6.3% of cases, aPL circulation was observed. In the control group, the rate was 3.4%.Conclusion: Considering the high percentage of aPL circulation in the case of IVF failures, authors think that high titers of aPL are a temporary contraindication for IVF. Patients with a history of aPL circulation are required to receive anticoagulant therapy from the first days of the hormonal protocol. The drug of choice is a group of low molecular weight heparins (LMWH). An individual approach is extremely important with the possible identification of causes of IVF failures and selective therapy, which leads to a significant improvement in the outcomes of the IVF program.


'It still leaves me sixty dollars out of pocket': experiences of diabetes medical care among low-income earners in Perth.
Diabetes prevalence is increasing in Australia, and there are stark inequities in prevalence and clinical outcomes experienced by Indigenous people and low socioeconomic groups compared with non-Indigenous and socioeconomically advantaged groups. This paper explores the impact of Indigenous status and socioeconomic disadvantage on the experience of diabetes care in the primary health setting. Data were collected through focus groups and interviews. The sample, comprising 38 participants (Indigenous and non-Indigenous), was recruited from disadvantaged areas in Perth, Australia. Data analysis was mainly deductive and based on a conceptual framework for the relationship between socioeconomic position and diabetes health outcomes. Most participants reported accessing general practitioners regularly; however, evidence of access to dietitians and podiatrists was very limited. Perceived need, cost, lack of information on available services and previous negative experiences influenced health care-seeking behaviour. Complexity and lack of coordination characterised the model of care reported by most participants. In contrast, Indigenous participants accessing an Aboriginal community-controlled health organisation reported a more accessible and coordinated experience of care. Our analysis suggests that Indigenous and socioeconomically disadvantaged people tailor their health care-seeking behaviour to the limitations imposed by their income and disadvantaged circumstances. To reduce inequities in care experiences, diabetes services in primary care need to be accessible and responsive to the needs of such groups in the community.


Evaluation of lidocaine and mepivacaine for inferior third molar surgery.
The aim of this study was to compare 2% lidocaine and 2% mepivacaine with 1:100,000 epinephrine for postoperative pain control. A group of 35 patients, both genders were recruited, whose had ages ranged from 13 to 27 years-old and had two inferior third molars in similar positions to be extracted. The cartridges were distributed to the patients according to a randomised pattern, where lidocaine was in the control group and mepivacaine in the experimental group. Results showed no significant association between the anesthetics and postoperative pain, pulp sensibility after one hour, gender, tooth position and duration of the surgical procedure. It was shown that lidocaine and mepivacaine have similar time of anesthesia, they are adequate for surgical procedures that last one hour, and there was no difference between the two anesthetics in relation to the severety of post-operative pain.


[Evaluative audiometry after cochlear implant provision. German Version].
One of the main treatment goals in cochlear implant (CI) patients is to improve speech perception. One of the target parameters is speech intelligibility in quiet. However, treatment results show a high variability, which has not been sufficiently explained so far. The aim of this noninterventional retrospective study was to elucidate this variability using a selected population of patients in whom etiology was not expected to have a negative impact on postoperative speech intelligibility. Audiometric findings of the CI follow-up of 28 adult patients after 6 months of CI experience were evaluated. These were related to the preoperative audiometric examination and evaluated with respect to a recently published predictive model for the postoperative monosyllabic score. Inclusion of postoperative categorical loudness scaling and hearing loss for Freiburg numbers in the model explained 55% of the variability in fitting outcomes with respect to monosyllabic comprehension. The results of this study suggest that much of the cause of variability in fitting outcomes can be captured by systematic postoperative audiometric checks. Immediate conclusions for CI system adjustments may be drawn from these results. However, the extent to which these are accepted by individual patients and thus lead to an improvement in outcome must be subject to further study, preferably prospective.


[Laser applications in dermatology].
Over the past decades continuous wave laser systems have been used in dermatology for the photocoagulation and vaporization of vascular neoformations and malformations and to remove epithelial lesions. However, their mainly thermal effect can have negative impact on wound healing and scar formation due to thermal damage of adjacent tissue. More recent laser systems now permit more selective and more restrictive destruction of pathological tissue. They include pulsed and Q-switched lasers matched to the absorption characteristics of the target structures, which permit skin ablation and selective photothermolosysis of pigmented or vascular lesions. These technical innovations have expanded the therapeutic spectrum in dermatology and improved the quality of the results achieved. Nevertheless, these systems should be used only for carefully selected indications, in particular when corrective-aesthetic considerations are of importance. Furthermore, prior to treatment, it is mandatory for the dermatologist, to establish the proper diagnosis, especially in the case of pigmented lesions and skin changes of uncertain dignity.


Role of Tumor-Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs).
This study evaluated the potential role of immune cells and molecules in the pathogenesis and clinical course of pancreatic neuroendocrine tumors (PanNET). Surgically resected PanNETs (N = 104) were immunohistochemically analyzed for Ki67 index, mitotic rate, macrophage, CD4+ cells, and CD8+ T-cell infiltration, as well as HLA class I, PD-L1, and B7-H3 expression. Results were correlated with clinicopathologic characteristics as well as with disease-free (DFS) and disease-specific (DSS) survival. The median age of the 57 WHO grade 1 and 47 WHO grade 2 patients was 55 years. High intratumoral CD8+ T-cell infiltration correlated with prolonged DFS (P = 0.05), especially when the number of tumor-associated macrophages (TAM) was low. In contrast, high peritumoral CD4+ cell and TAM infiltration was associated with a worse DFS and DSS. PD-L1 and B7-H3 were expressed in 53% and 78% PanNETs, respectively. HLA class I expression was defective in about 70% PanNETs. HLA-A expression correlated with favorable DSS in PD-L1-negative tumors (P = 0.02). TAM infiltration (P = 0.02), WHO grade (P = 0.04), T stage (P = 0.01), and lymph node positivity (P = 0.04) were independent predictors of DFS. TAM infiltration (P = 0.026) and T stage (P = 0.012) continued to be predictors of DFS in WHO grade 1 PanNET patients. TAM infiltration was the sole independent predictor of DSS for WHO grade 1 and 2 patients (P = 0.02). Therefore, this biomarker may contribute to identifying WHO grade 1 patients with poor prognosis. TAM infiltration appears to be the most informative prognostic biomarker in PanNET. It may represent a useful immunotherapeutic target in patients with PanNET.


Ischemic time and free flap success.
Ischemic time (the time between the interruption and reestablishment of blood supply) was reviewed for 700 free flaps used for breast or head and neck reconstruction. Flaps that failed had a mean ischemic time of 111.64 minutes, while flaps that survived had a mean ischemic time of 91.25 minutes. The difference was not statistically significant (p = 0.189). The patients were then divided into two groups: those with flap ischemic times of 100 minutes or longer and those with flap ischemic times less than 100 minutes. We found that flap survival was similar in the two groups. Flap survival was also similar when 75 minutes and 120 minutes were used to segregate the longer and shorter ischemic time groups. When 180 minutes was used to segregate the groups, there was a slight trend toward more flap loss in the group with longer ischemic time, but the difference was not significant. We conclude that ischemic time is irrelevant to flap survival, provided that ischemia is not prolonged past 3 hours or to the point where the no-reflow phenomenon occurs.


Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.
Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 μg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.


Rapid in vivo transport and catabolism of human apolipoprotein A-IV-1 and slower catabolism of the apoA-IV-2 isoprotein.
Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins (HDL). ApoA-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly understood. In order to gain insight into factors modulating apoA-IV metabolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidemic human subjects. 131I-apoA-IV-1 and 125I-apoA-IV-2 were reassociated with autologous plasma and injected into study subjects. Analysis of the kinetic data revealed a rapid mean fractional catabolic rate (FCR) for apoA-IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transport, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV concentrations were highly correlated with apoA-IV production rate (r = 0.84, P < 0.001) and not correlated with apoA-IV fractional catabolic rate (r = 0.25, P = NS). The mean FCR of apoA-IV-2 was 2.21 +/- 0.10 d-1. In the ten subjects in whom 131I-apoA-IV-1 and 125I-apoA-IV-2 were simultaneously injected, the FCR of apoA-IV-2 was significantly slower by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apolipoprotein in humans, with a fractional catabolic rate more than 10 times greater than that of apoA-I; (b) apoA-IV has a high absolute transport rate similar to that of apoA-I; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subjects; and (d) the fractional catabolic rate of the common variant apoA-IV-2 is slower than that of the wild-type apoA-IV-1.


Compartment pressures after submuscular fixation of proximal tibia fractures.
Tibial fractures are known to be associated with elevated compartment pressures, which may potentially result in a compartment syndrome. The Tibial Less Invasive Stabilization System (LISS PLT) is an internal fixator device that is designed for fixation of proximal tibia fractures. The technique includes submuscular placement of the implant along the lateral border of the tibia. Such placement of the Tibia LISS into the anterior leg compartment could increase compartment pressures, and therefore increase the risk of compartment syndrome. The objective of this prospective study is to determine whether submuscular placement of a tibia LISS fixator increases compartment pressures and what is the incidence of compartment syndrome. Twenty-eight consecutive proximal tibia fractures were fixed using the Tibia LISS (LISS PLT). Compartment pressures in all four leg compartments were measured pre- and postoperatively. Diastolic pressures were recorded and perfusion pressures calculated. There were no statistically significant differences between pre- and postoperative compartment pressures. One patient out of twenty-eight developed an impending compartment syndrome after placement of the LISS implant. Submuscular fixation of the tibia with the Less Invasive Stabilization System does not cause a significant rise in leg compartment pressures, nor is it associated with an increased incidence of compartment syndrome.


Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.
Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.


Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects.
Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.


[Resistance surveillance of Neisseria gonorrhoeae in a hospital in Santa Fe province, Argentina: 1997-2004].
Resistance phenotypes characterized by minimum inhibitory concentration, disk diffusion and beta-lactamase production were determined in 434 isolates from patients attending the Sexually Transmitted Disease Service at Dr. José Maria Cullen Hospital in Santa Fe, Argentina. Susceptibility tests to penicillin, tetracycline, ciprofloxacin, espectinomycin, azithromycin and ceftriaxone were performed. Pulsed-field gel electrophoresis was conducted made to on three ciprofloxacin-resistant isolates. Epidemiologically speaking, three interesting events should be highlighted: during 1997, plasmid-mediated high level tetracycline-resistant strains were observed (33.3%); from 2002 to 2004 a significant increase of plasmid-mediated penicillin-resistant strains was registered (9.7% to 34.8%); and in the year 2000 the first two quinolone-resistant strains emerged in the province. In our hospital, the first azithromycin-resistant isolate emerged in 2004. We therefore emphasize the importance of the Clinical Microbiology Laboratory in order to provide information for the empiric treatment of this infection.


Abbreviated Biparametric Prostate MR Imaging in Men with Elevated Prostate-specific Antigen.
Purpose To determine the diagnostic accuracy for clinically significant prostate cancer achieved with abbreviated biparametric prostate magnetic resonance (MR) imaging in comparison with full multiparametric contrast material-enhanced prostate MR imaging in men with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (US)-guided biopsy findings; to determine the significant cancer detection rate of biparametric versus full multiparametric contrast-enhanced MR imaging and between-reader agreement for interpretation of biparametric MR imaging. Materials and Methods In this institutional review board-approved retrospective review of prospectively acquired data, men with PSA greater than or equal to 3 ng/mL after negative transrectal US-guided biopsy findings underwent state-of-the-art, full multiparametric contrast-enhanced MR imaging at 3.0-T including high-spatial-resolution structural imaging in several planes, diffusion-weighted imaging at 0, 800, 1000, and 1400 mm2/sec, and dynamic contrast-enhanced MR imaging, obtained without endorectal coil within 34 minutes 19 seconds. One of four radiologists with different levels of expertise (1-9 years) first reviewed only a fraction of the full multiparametric contrast-enhanced MR images, consisting of single-plane (axial) structural imaging (T2-weighted turbo spin-echo and diffusion-weighted imaging), acquired within 8 minutes 45 seconds (referred to as biparametric MR imaging), and established a diagnosis according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2; only thereafter, the remaining full multiparametric contrast-enhanced MR images were read. Men with PI-RADS categories 3-5 underwent MR-guided targeted biopsy. Men with PI-RADS categories 1-2 remained in urologic follow-up for at least 2 years, with rebiopsy (transrectal US-guided or transperineal saturation) where appropriate. McNemar test was used to compare diagnostic accuracies. To investigate between-reader agreement, biparametric MR images of 100 patients were read independently by all three radiologists. Results A total of 542 men, aged 64.8 years ± 8.2 (median PSA, 7 ng/mL), were included. Biparametric MR imaging helped detect clinically significant prostate cancer in 138 men. Full multiparametric contrast-enhanced MR imaging allowed detection of one additional clinically significant prostate cancer (a stage pT2a, intermediate-risk cancer with a Gleason score of 3+4) and caused 11 additional false-positive diagnoses. Diagnostic accuracy for detection of clinically significant cancer of biparametric MR imaging (89.1%, 483 of 542) was similar to that of full multiparametric contrast-enhanced MR imaging (87.2%, 473 of 542). Between-reader agreement of biparametric MR imaging interpretation was substantial (κ = 0.81). Conclusion Biparametric MR imaging allows detection of clinically significant prostate cancer missed by transrectal US-guided biopsy. Biparametric prostate MR imaging takes less than 9 minutes examination time, works without contrast agent injection, and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MR imaging protocols. © RSNA, 2017.


Mobility-induced order in active XY spins on a substrate.
We elucidate that the nearly phase-ordered active XY spins in contact with a conserved, diffusing species on a substrate can be stable. For wide-ranging model parameters, it has stable uniform phases robust against noises. These are distinguished by generalized quasi-long-range (QLRO) orientational order logarithmically stronger or weaker than the well-known QLRO in equilibrium, together with miniscule (i.e., hyperuniform) or giant number fluctuations, respectively. This illustrates a direct correspondence between the two. The scaling of both phase and density fluctuations in the stable phase-ordered states is nonuniversal: they depend on the nonlinear dynamical couplings. For other parameters, it has no stable uniformly ordered phase. Our model, a theory for active spinners, provides a minimal framework for wide-ranging systems, e.g., active superfluids on substrates, synchronization of oscillators, active carpets of cilia and bacterial flagella, and active membranes.


Strong π-Backbonding Enables Record Magnetic Exchange Coupling Through Cyanide.
The paramagnetic cyano-bridged complex PhB(tBuIm)3Fe-NC-Mo(NtBuAr)3 (Ar = 3,5-Me2C6H3) is readily assembled from a new four-coordinate, high-spin (S = 2) iron(II) monocyanide complex and the three-coordinate molybdenum(III) complex Mo(NtBuAr)3. X-ray diffraction and IR spectroscopy reveal that delocalization of unpaired electron density into the cyanide π* orbitals leads to a reduction of the C-N bond order. Direct current (dc) magnetic susceptibility measurements, supported by electronic structure calculations, demonstrate the presence of strong antiferromagnetic exchange between spin centers, with a coupling constant of J = -122(2) cm-1. To our knowledge, this value represents the strongest magnetic exchange coupling ever to be observed through cyanide. These results demonstrate the ability of low-coordinate metal fragments to engender extremely strong magnetic exchange coupling through cyanide by virtue of significant π-backbonding into the cyanide ligand.


Nitric oxide associated protein 1 is associated with chloroplast perturbation and disease symptoms in Nicotiana benthamiana infected with South African cassava mosaic virus.
Nitric oxide associated 1 (NOA1) in plants is a cyclic GTPase involved in protein translation in the chloroplast and has been indirectly linked to nitric oxide (NO) accumulation and response to biotic stress. The association between NOA1 and NO accumulation in Arabidopsis noa1 mutants has been linked to the inability of noa1 mutants to accumulate carbon reserves such as fumarate, leading to chloroplast dysfunction and a pale green leaf phenotype. To understand the role played by NOA1 in response to South African cassava mosaic virus infection in Nicotiana benthamiana, the expression of NbNOA1 and the accumulation of NO in leaf samples was compared between south african cassava mosaic (SACMV)-infected and mock-infected plants at 14 and 28 dpi. Real-time qPCR was used to measure SACMV viral load which increased significantly by 20% from 14 to 28 dpi as chlorosis and symptom severity progressed. At 14 and 28 dpi, NbNOA1 expression was significantly lower than mock inoculated plants (2-fold lower at 14 dpi, p-value=0.01 and 5-fold lower at 28, p-value=0.00). At 14 dpi, NO accumulation remained unchanged in infected leaf tissue compared to mock inoculated, while at 28 dpi, NO accumulation was 40% lower (p-value=0.01). At 28 dpi, the decrease in NbNOA1 expression and NO accumulation was accompanied by chloroplast dysfunction, evident from the significant reduction in chlorophylls a and b and carotenoids in SACMV-infected leaves. Furthermore, the expression of chloroplast translation factors (chloroplast RNA binding, chloroplast elongation factor G, translation elongation factor Tu, translation initiation factor 3-2, plastid-specific ribosomal protein 6 and plastid ribosome recycling factor) were found to be repressed in infected N. benthamiana. GC-MS analysis showed a decrease in fumarate and an increase in glucose in SACMV-infected N. benthamiana in comparison to mock samples suggesting a decrease in carbon stores. Collectively, these results provide evidence that in response to SACMV infection, a decrease in photopigments and carbon stores, accompanied by an increase in glucose and decrease in fumarate, leads to a decline in NbNOA1expression and NO levels. This is manifested by suppressed translation factors and disruption of chloroplast function, thereby contributing to chlorotic disease symptoms.


An investigation into enlarging and reducing the size of mirror reflections of the hand on experimentally-induced cold-pressor pain in healthy human participants.
Mirror visual feedback may be a useful clinical tool for reducing pain. Research suggests that reducing the size of a non-painful reflected hand can alleviate complex regional pain syndrome in the affected hand that is out of view. In contrast, research on healthy humans exposed to experimentally induced pain suggests that reducing the appearance of the size of a reflected body part can increase pain. The aim of this study was to investigate the effect of enlarging and reducing the visual appearance of the size of a hand using mirror visual feedback on pain threshold, intensity and tolerance in healthy human participants exposed to cold-pressor pain. Participants were a convenience sample of 20 unpaid, healthy pain free volunteers aged 18 years or above. Each participant took part in one experiment where they completed cold-pressor pain tests whilst observing normal, enlarged and reduced size reflections of a hand congruent to a hand immersed in the ice cold water. A 4×2 factorial repeated measures analysis of variance (ANOVA) was performed on time to pain threshold and pain tolerance, and pain intensity with Condition (four levels: no reflection, reduced reflection, normal reflection, enlarged reflection) being the within-subject factors and Sex (two levels: female, male) between-subject factors. There were no significant effects for Condition, Sex, or Condition×Sex interaction for pain threshold, intensity or tolerance (p>0.05). There were no significant differences between the 3 mirror reflection conditions for agreement with the statements: "It felt like I was looking directly at my hand rather than at a mirror image"; "It felt like the hand I was looking at was my hand"; and "Did it seem like the hand you saw was a right hand or a left hand?". Enlarging or reducing the size of a hand using mirror visual feedback did not alter pain perception in healthy human participants exposed to cold-pressor pain. The different sizes of hands generated by mirror visual feedback created an illusion of looking at their own hand but this was not as strong as looking directly at the hand. In future, investigators and clinicians using mirror visual feedback may consider including an adaptive phase to ensure the reflection has been perceptually embodied. Reasons for the lack of effects are explored to inspire further research in the field.


Prediction of whelping date in large and giant canine breeds by ultrasonography foetal biometry.
To derive the growth curves of the inner chorionic cavity and the biparietal diameter in large and giant dog breeds by ultrasonographic foetal biometry. To evaluate their accuracy in the prediction of whelping date and the effect of litter size and foetal sex ratio. Foetal biometry parameters were obtained using serial ultrasonographic examinations in eight large (26 to 40 kg) and nine giant (>40 kg) pregnant bitches with known breeding dates and concentrations of serum progesterone during oestrus. The relationship between inner chorionic cavity or biparietal diameter growth and days to parturition were analysed by linear regression and the equations derived from the growth curves were applied to predict the whelping day. The accuracy of the prediction (whelping day ±1 day and ±2 days) and the litter size and sex ratio were recorded. The results showed a significant relationship between days before parturition and inner chorionic cavity or biparietal diameter. The overall accuracy at ±2 days was greater, than that at ±1 day. In giant breed bitches, the accuracy of the prediction by biparietal diameter was significantly lower in small, than normal litter size. No effect of foetal sex ratio was observed. Foetal biometry parameters obtained by ultrasonography can be used to predict whelping dates in large and giant dog breeds.


Marriage Matters But How Much? Marital Centrality Among Young Adults.
Marriage, once a gateway to adulthood, is no longer as widely considered a requirement for achieving adult status. With declining marriage rates and delayed marital transitions, some have wondered whether current young adults have rejected the traditional notion of marriage. Utilizing a sample of 571 young adults, the present study explored how marital centrality (the expected importance to be placed on the marital role relative to other adult roles) functioned as a unique and previously unexplored marital belief among young adults. Results suggested that marriage remains an important role for many young adults. On average, young adults expected that marriage would be more important to their life than parenting, careers, or leisure activities. Marital centrality profiles were found to significantly differ based on both gender and religiosity. Marital centrality was also associated with various outcomes including binge-drinking and sexual activity. Specifically, the more central marriage was expected to be, the less young adults engaged in risk-taking or sexual behaviors.


A home-based progressive resistance exercise programme for patients with venous leg ulcers: a feasibility study.
This study aimed to assess the feasibility of a home-based exercise programme and examine the effects on the healing rates of venous leg ulcers. A 12-week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow-up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (P = 0·34) than the usual care group, and a 10% (P = 0·74) improvement in the number of participants healed in the intervention group compared to the usual care group. Significant differences between groups over time were observed in calf muscle pump function parameters [ejection fraction (P = 0·05), residual volume fraction (P = 0·04)] and range of ankle motion (P = 0·01). This pilot study is one of the first to examine and measure clinical healing rates for participants involved in a home-based progressive resistance exercise programme. Further research is warranted with a larger multi-site study.


The frequency of the A gamma T gene in the presence and absence of the beta S or beta C gene in the Black population of the Southeastern USA.
Quantitative information about the three types of gamma chains (A gamma T, A gamma I, G gamma) has been obtained for the Hb F from 285 normal Black babies, 172 babies with a Hb S or Hb C heterogeneity, and from 150 babies and older patients with the SS, SC, or CC conditions by means of a high pressure liquid chromatographic microprocedure. The frequency of the A gamma T gene in the AA babies was 0.1035, while that in the SS patients was a low 0.0362. This low A gamma T frequency in the SS population adequately explains the lower percentage (13.2%) of A gamma T heterozygotes among AS newborn babies as compared to 17.9% among AA babies. The genotype with the A gamma T mutant in trans to the beta S mutation is presumed to occur about three times more frequently than that in which the A gamma T mutant is in cis to the beta S mutation. A study of family members of one SS patients who has an A gamma T homozygosity provided data supporting linkage of the A gamma T and beta S anomalies in some Hb S heterozygotes.


Cellular automata on high-dimensional hypercubes.
The emergence of nontrivial collective behavior is studied in large families of cellular automata rules implemented on high-dimensional hypercubes. Evidence is found that the region of rule space where such macroscopic dynamics exists is well-defined in the infinite-dimension limit.


Use of a cane for ambulation: marker and mitigator of impairment in older people who report no difficulty walking.
To measure disability, patients are often asked whether they have difficulty performing daily tasks. However, recent work suggests that functional problems may be detected earlier by inquiring about modifications in the way tasks are performed. We sought to describe the characteristics of older people who deny difficulty walking but nevertheless have modified the manner in which they walk, by use of a cane. We also tested the hypothesis that, among older people who deny difficulty walking, those using a cane have more mobility problems and are at greater risk for future mobility problems than those not using a cane. Longitudinal survey study, with measures at baseline and 2-year follow-up. Population-based survey of urban older people. One thousand two hundred fifty-one community-dwelling older persons without severe cognitive impairment who reported no difficulty walking at baseline. Self-reported health, activities of daily living (ADL), and mobility status. Among older people who denied difficulty walking, those who used a cane at baseline (7 of subjects) were older and more likely to have taken medication for a heart condition or arthritis, to have an ADL deficit, and to have been hospitalized in the past year. They were less likely to have walked for pleasure in the past month and more likely to report difficulty crossing roads or intersections. Moreover, those using a cane at baseline were more likely to develop new mobility problems at follow-up. For example, 15 of those who used a cane at baseline reported new difficulty walking at follow-up, compared with 2 of those who did not use a cane. Older people who deny difficulty walking but who use a cane are at greater risk than those who do not use a cane for the development of difficulty walking and other new mobility problems. Asking patients about task modification rather than difficulty alone may be a more sensitive way to detect early or mild functional problems.


[Effects of bilateral lung volume reduction surgery in a patient with severe pulmonary emphysema].
A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume reduction surgery on both upper lobes. By one year after surgery functional residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of 2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had increased and ventilation and pulmonary gas exchange had improved. Performance on a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were abnormally high, but 6 months after the operation the increases in Ppa and Pcwp during exercise were markedly reduced.


UNPREDICTABILITY OF CORRELATED RESPONSE TO SELECTION: LINKAGE AND INITIAL FREQUENCY ALSO MATTER.
In a recent paper, Gromko (1995) showed using computer simulations that pleiotropy and sampling interact to generate variation in correlated response to selection. His simulations demonstrated that different combinations of pleiotropic effects could lead to the same genetic correlation value, yet, as long as the population size and correlation value were large enough, result in significantly different variance of correlated responses after 10 generations of selection. We extended those results using Alan Roberston's "reparameterization" of selection processes in finite populations. As for direct selection response, a satisfactory description of the correlated response and its variability can be expressed in terms of Nih, t/N, and NL, where N is the effective population size, i is the selection intensity in standard units, h2 is the heritability of the selected and correlated traits, t is the number of generations, and L is the length of the chromosome in map units. For a given number of loci, there exits an Nih threshold under which differences between pleiotropic systems will not be detected. For values of Nih above this threshold, the higher Nih is the smaller t/N needs to be for significant differences in correlated responses between pleiotropic systems to be observed. A large number of loci or tight linkage increases the unpredictability of the correlated response, but if Nih is large enough, it does not absolutely prevent significant differences between pleiotropic systems to occur. On the other hand, a small initial allele frequency of the favorable allele would tend to cancel the differences between pleiotropic systems, even for large values of Nih and t/N. Finally, epistasis decreases the overall variability of the correlated response, but generally preserves the difference between pleiotropic systems. Thus, Gromko's conclusions on the unpredictability of correlated response due to variable pleiotropy seem fairly robust, at least in the long term.


Thyroid cancer in childhood: a retrospective review of childhood course.
Thyroid cancer (TC) is an uncommon childhood malignancy, but the incidence may be increasing. Recent American Thyroid Association guidelines focus primarily on adult data. Natural history studies of TC in childhood are important to determine outcomes. The objectives of this study were to describe the demographics and outcomes in children with TC treated at The Hospital for Sick Children, Toronto, from 1983 to 2006. We hypothesized that childhood TC was increasing at our institution. Cases of papillary TC (PTC) (including follicular variant PTC) and follicular TC (FTC) were identified from pathology databases. Chart review was performed, and data were extracted on clinical, treatment, and outcome variables. Sixty-one cases were identified, and complete data were available in 54, including 36 girls and 18 boys. There was no statistical change in numbers of cases diagnosed yearly during the study period. Younger children were more likely to have metastases at presentation or during follow-up. Pathological TC diagnosis included 40 PTC, 1 diffuse-sclerosing papillary, 7 follicular variant PTC, and 6 FTC. There was no difference in pathology findings between children less than or greater than 10 years old. Five patients had a history of previous malignancy, and five had a history of previous thyroid conditions. Three patients were born in areas of high TC endemnicity. Twenty-three patients had thyroiditis on pathology examination. All patients underwent total thyroidectomy, and 53/54 patients received therapeutic radioactive iodine ablation. Twenty-seven patients had metastases at presentation (19 lymph nodes only, 2 lung only, and 6 lymph node and distant) and 6 developed distant metastases during follow-up (3 lung, 2 thymus, and 1 paraspinal). Male sex was associated with development of metastases during follow-up. On multiple regression, tumor size was predicted positively by PTC but not by age, sex, or metastases at presentation or during follow-up. We did not find evidence of increasing numbers of cases of TC diagnosed yearly during the study period, or difference in tumor aggressiveness, or between outcomes in children aged less than or greater than 10 years. Children with metastases at presentation or during follow-up were likely to be younger than children without metastases. There is a need for prospective, collaborative multicenter studies of TC.


Visualization, imaging and new preclinical diagnostics in radiation oncology.
Innovative strategies in cancer radiotherapy are stimulated by the growing knowledge on cellular and molecular tumor biology, tumor pathophysiology, and tumor microenvironment. In terms of tumor diagnostics and therapy monitoring, the reliable delineation of tumor boundaries and the assessment of tumor heterogeneity are increasingly complemented by the non-invasive characterization of functional and molecular processes, moving preclinical and clinical imaging from solely assessing tumor morphology towards the visualization of physiological and pathophysiological processes. Functional and molecular imaging techniques allow for the non-invasive characterization of tissues in vivo, using different modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and optical imaging (OI). With novel therapeutic concepts combining optimized radiotherapy with molecularly targeted agents focusing on tumor cell proliferation, angiogenesis, and cell death, the non-invasive assessment of tumor microcirculation and tissue water diffusion, together with strategies for imaging the mechanisms of cellular injury and repair is of particular interest. Characterizing the tumor microenvironment prior to and in response to irradiation will help to optimize the outcome of radiotherapy. These novel concepts of personalized multi-modal cancer therapy require careful pre-treatment stratification as well as a timely and efficient therapy monitoring to maximize patient benefit on an individual basis. Functional and molecular imaging techniques are key in this regard to open novel opportunities for exploring and understanding the underlying mechanisms with the perspective to optimize therapeutic concepts and translate them into a personalized form of radiotherapy in the near future.


Computational Theories of Alcohol Use Disorder: Mapping Learning and Choice Mechanisms on Symptoms.
Alcohol use disorder (AUD) is characterized by a combination of symptoms including excessive craving, loss of control, and progressive neglect of alternative pleasures. A mechanistic understanding of what drives these symptoms is needed to improve diagnostic stratification and to develop new treatment and prevention strategies for AUD. To date, there is no consensus regarding a unifying mechanistic framework that accounts for the different symptoms of AUD. Reinforcement learning (RL) and economic choice theories may be key to elucidating the underlying processes of symptom development and maintenance in AUD. These algorithms may account for the different behavioral and physiological phenomena and are suited to dissect mechanisms linked to different symptoms of AUD. We here review different RL and economic choice models and how they map onto three symptoms of AUD: (1) cue-induced craving, (2) neglect of alternative rewards, and (3) consumption despite adverse consequences. For each symptom and theory, we describe findings from animal and human studies. In humans, we focus on empirical studies that investigated RL models in the context of treatment outcome in AUD. The review indicates important gaps to be addressed in the future by highlighting the challenges in transferring findings from RL and economic choice studies to clinical application. We also critically evaluate the potential and pitfalls of a symptom-oriented approach and highlight the importance of elucidating the role of learning and decision-making processes across diagnostic boundaries.


Influence of photo-activation source on enamel demineralization around restorative materials.
This study evaluated the effects of the photoactivation source and restorative material on the development of caries-like lesions on human enamel after an in vitro pH challenge. Enamel cavities were prepared in 36 blocks, which were assigned to two groups according to the restorative material: resin-modified glass ionomer (RMGI) and composite resin (CR). Samples were exposed to quartz-tungsten-halogen lamp, argon-ion laser, or light-emitting diode (n = 6). The Knoop microhardness (KHN) values of the top surface of all materials were evaluated. Restored enamel blocks were thermocycled and subjected to 10 demineralization-remineralization cycles at 37°C. KHN analysis of the superficial enamel was performed by four indentations located 100 μm from the restoration margin. The material KHN was not affected by the photoactivation source. No significant difference in KHN was noted between CR and RMGI. The enamel surface around RMGI exhibited a higher KHN (272.8 KHN) than the enamel around CR (93.3 KHN), regardless of the photoactivation source. Enamel demineralization around the dental restoration was not influenced by the photoactivation source. Less enamel demineralization was observed around the RMGI than around the CR restoration.


Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
We present a RNA deep sequencing (RNAseq) analysis of a comparison of the transcriptome responses to infection of zebrafish larvae with Staphylococcus epidermidis and Mycobacterium marinum bacteria. We show how our developed GeneTiles software can improve RNAseq analysis approaches by more confidently identifying a large set of markers upon infection with these bacteria. For analysis of RNAseq data currently, software programs such as Bowtie2 and Samtools are indispensable. However, these programs that are designed for a LINUX environment require some dedicated programming skills and have no options for visualisation of the resulting mapped sequence reads. Especially with large data sets, this makes the analysis time consuming and difficult for non-expert users. We have applied the GeneTiles software to the analysis of previously published and newly obtained RNAseq datasets of our zebrafish infection model, and we have shown the applicability of this approach also to published RNAseq datasets of other organisms by comparing our data with a published mammalian infection study. In addition, we have implemented the DEXSeq module in the GeneTiles software to identify genes, such as glucagon A, that are differentially spliced under infection conditions. In the analysis of our RNAseq data, this has led to the possibility to improve the size of data sets that could be efficiently compared without using problem-dedicated programs, leading to a quick identification of marker sets. Therefore, this approach will also be highly useful for transcriptome analyses of other organisms for which well-characterised genomes are available.


Design, construction, and evaluation of an inhalation system for exposing experimental animals to environmental tobacco smoke.
An inhalation system was designed to expose experimental animals to aged and diluted sidestream smoke (ADSS), used as a surrogate for environmental tobacco smoke (ETS). The construction of the smoke generator and of the smoke dilution systems is described. Target ADSS concentrations in a 90-day inhalation study were 0.1, 1, and 10 mg/m3 of respirable suspended particulates (RSP). Data is presented on the physical and chemical composition of the smoke presented to animals at or near these target RSP concentrations. The design of the inhalation laboratory was shown to result in highly reproducible respirable aerosols that were effective surrogates of ETS.


Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer.
The antitumor activity of IFN-alpha is well established. However, the role of the plasmacytoid dendritic cell (PDC), the major producer of IFN-alpha upon viral infection, in tumor biology is unknown. We sought to study the presence and function of PDC in a human solid tumor. Here, we demonstrate that PDCs infiltrate tumor tissue of patients with head and neck squamous cell carcinoma (HNSCC). Functional activity of PDC was examined by using CpG motif containing oligonucleotides, a defined microbial stimulus for PDCs (recognized via toll-like receptor 9). We found that HNSCC diminished the ability of PDC to produce IFN-alpha in response to CpG motif containing oligonucleotide. Tumor-induced down-regulation of toll-like receptor 9 was identified as one mechanism likely contributing to impaired PDC function within the tumor environment. In tumor-draining lymph nodes, suppression of CpG-induced IFN-alpha production was less pronounced than in single-cell suspensions of primary tumor tissue. In these lymph nodes, CpG-induced IFN-alpha production was associated with increased levels of interferon-induced protein 10 and IFN-gamma and activation of CD4 and CD8 T cells. These results show for the first time the presence of PDCs in human solid tumor tissue and that tumors suppress the capacity of PDCs to produce IFN-alpha. PDCs, which in the absence of appropriate stimulation are reported to promote regulatory CD8 T cells, may contribute to an impaired T-cell-mediated immune response in HNSCC.


Release and action of epidermal growth factor on gastric secretion in humans.
Epidermal growth factor (EGF) has recently been localized in salivary, pancreatic, and Brunner's glands in humans, but little is known about its release and its action on gastric secretion. This study, performed on healthy subjects, was designed to determine the release of immunoreactive EGF in plasma and in salivary and gastric secretions under basal conditions and after modified sham feeding (MSF), ordinary feeding, and infusion of pentagastrin without and with addition of exogenous recombinant human EGF (hEGF). Under basal conditions the EGF concentrations in plasma and salivary and gastric secretions were 52 +/- 8 pg/ml, 2.5 +/- 0.3 ng/ml, and 0.12 +/- 0.03 ng/ml, respectively. MSF and ordinary feeding increased significantly EGF plasma level and salivary output but not gastric EGF output, and atropinization failed to effect these plasma and salivary EGF responses to MSF. Intravenous infusion of pentagastrin increased both plasma and salivary but not gastric EGF, and addition of exogenous hEGF in graded doses (0.25-1.0 micrograms/kg) resulted in a dose-dependent increase in the plasma level of EGF and in significant inhibition of gastric acid and pepsin outputs. The increment in plasma EGF, which resulted in significant inhibition of gastric secretion, was several times greater than that observed after MSF or feeding. EGF infused in a constant dose (0.12 or 1.0 micrograms/kg-h) resulted in an increment in plasma EGF similar to that observed after MSF alone.


Ultraviolet filters.
The chemistry, photostability and mechanism of action of ultraviolet filters are reviewed. The worldwide regulatory status of the 55 approved ultraviolet filters and their optical properties are documented. The photostabilty of butyl methoxydibenzoyl methane (avobenzone) is considered and methods to stabilize it in cosmetic formulations are presented.


Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.
Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.